Density abnormalities in normal-appearing gray matter in the middle-aged brain with white matter hyperintense lesions: a DARTEL-enhanced voxel-based morphometry study

Abstract

Background and purpose

Little is known about the structural alterations within gray matter (GM) in middle-aged subjects with white matter hyperintense (WMH) lesions. Here, we aimed to examine the anatomical changes within the GM and their relationship to WMH lesion loads in middle-aged subjects.

Participants and methods

Twenty-three middle-aged subjects with WMH lesions (WMH group) and 23 demographically matched healthy control subjects participated in the study. A Diffeomorphic Anatomical Registration Through Exponentiated Liealgebra-enhanced voxel-based morphometry was used to measure the GM density, and the correlations between WMH lesion volume and extracted GM values in abnormal regions were identified by voxel-based morphometry analysis.

Results

Compared with the healthy control subjects, the WMH group had a significantly decreased GM density in the left middle frontal gyrus, bilateral anterior cingulate cortex, left and right premotor cortex, and left and right middle cingulate cortex and an increased GM density in the bilateral cerebellum anterior lobe, left middle temporal gyrus, right temporoparietal junction, left and right prefrontal cortex (PFC), and left inferior parietal lobule. A relationship was observed between the normalized WMH lesion volume and the decreased GM density, including the left middle frontal gyrus (ρ=−0.629, P=0.002), bilateral anterior cingulate cortex (ρ=−0.507, P=0.019), right middle cingulate cortex (ρ=−0.484, P=0.026), and right premotor cortex (ρ=−0.438, P=0.047). The WMH lesion loads also negatively correlated with increased GM density in the right temporoparietal junction (ρ=−0.484, P=0.026), left PFC (ρ=−0.469, P=0.032), and right PFC (ρ=−0.438, P=0.047).

Conclusion

We observed that lesion load-associated structural plasticity corresponds to bidirectional changes in regional GM density in the WMH group.

Keywords:

• white matter hyperintense lesion
• voxel-based morphometry
• normal-appearing gray matter
• aging

Supplementary material

Table S1 Partial correlation of WMH parameter and extracted GM density values in abnormal regions identified by VBM analysis (ρ/P-values)

Acknowledgments

The authors thank their patients and volunteers for participating in this study. This study was supported by the National Science Foundation of China (grant nos 81101041 and 81560284), the Natural Science Foundation of Jiangxi, People’s Republic of China (grant no 2013BAB215008), the Science and Technology Project of Jiangxi Provincial Education Department, People’s Republic of China (grant no GJJ13136), and also by the Science and Technology Project of Jiangxi Provincial Health and Family Planning Commission (grant no 20143071).

Author contributions

FZ contributed to study concept and design and manuscript writing. LW, YP, and SL contributed to data acquisition. YP, SL, XL, and YZ contributed to analysis and interpretation of the data. YP, FZ, XL, and SL contributed to manuscript edits. FZ and DL contributed to study supervision. All authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work. None of the authors have any personal or financial involvement with organizations that have a financial interest in its content.