Abnormal whole-brain voxelwise structure-function coupling and its association with cognitive dysfunction in patients with different cerebral small vessel disease burdens

Cerebral small vessel disease (CSVD) is a universal neurological disorder in older adults that occurs in connection with cognitive dysfunction and is a chief risk factor for dementia and stroke. While whole-brain voxelwise structural and functional abnormalities in CSVD have been heavily explored, the degree of structure-function coupling abnormality possible in patients with different CSVD burdens remains largely unknown. This study included 53 patients with severe CSVD burden (CSVD-s), 108 patients with mild CSVD burden (CSVD-m) and 76 healthy controls. A voxelwise coupling metric of low frequency fluctuations (ALFF) and voxel-based morphometry (VBM) was used to research the important differences in whole-brain structure-function coupling among groups. The correlations between ALFF/VBM decoupling and cognitive parameters in CSVD patients were then investigated. We found that compared with healthy controls, CSVD-s patients presented notably decreased ALFF/VBM coupling in the bilateral caudate nuclei and increased coupling in the right inferior temporal gyrus (ITG). In addition, compared with the CSVD-m group, the CSVD-s group demonstrated significantly decreased coupling in the bilateral caudate nuclei, right putamen and inferior frontal gyrus (IFG) and increased coupling in the left middle frontal gyrus and medial superior frontal gyrus. Notably, the ALFF/VBM decoupling values in the caudate, IFG and ITG not only showed significant correlations with attention and executive functions in CSVD patients but also prominently distinguished CSVD-s patients from CSVD-m patients and healthy controls in receiver operating characteristic curve research. Our discoveries demonstrated that decreased ALFF/VBM coupling in the basal ganglia and increased coupling in the frontotemporal lobes were connected with more severe burden and worse cognitive decline in CSVD patients. ALFF/VBM coupling might serve as a novel effective neuroimaging biomarker of CSVD burden and provide new insights into the pathophysiological mechanisms of the clinical development of CSVD.