Investigating Brain Network Characteristics Interrupted by Covert White Matter Injury in Patients with Moyamoya Disease: Insights from Graph Theoretical Analysis.

Chronic ischemia in adult moyamoya disease (MMD) reduces the integrity of normal-appearing white matter (WM). We investigated whether covert WM impairment alters large-scale brain networks and specific neural circuits associated with neurocognitive dysfunction in MMD. Forty-six participants (control, n = 23; MMD, n = 23) were examined using diffusion tensor imaging and streamline tractography. Structural connectivity among 90 cortical and subcortical brain regions was evaluated using the mean fractional anisotropy along the fiber tracts. Graph theoretical analysis was used to measure network parameters and inter-regional connectivity. Global network parameters were reduced in patients with MMD, including cluster coefficient (controls vs. MMD: 3.62 ± 0.24 vs. 3.26 ± 0.36; P < 0.0001), characteristic path length (controls vs. MMD: 1.20 ± 0.02 vs. 1.17 ± 0.01; P < 0.001), and small-world property (controls vs. MMD: 3.07 ± 0.18 vs. 2.83 ± 0.27; P < 0.001). Reduced pairwise connectivity was found in prefrontal neural circuits within the middle/inferior frontal gyrus; supplementary motor area; and insular, inferior temporal, and dorsal cingulate cortices. Covert WM microstructural changes in patients with MMD alter large-scale brain networks, as well as lateral prefrontal neural circuits. Evaluation of structural connectivity may be useful to assess the severity of chronic ischemic injury from a network perspective.