Brain network communication model reveals diffusion-based structure-function decoupling in mild cognitive impairment

Brain structural (SC) and functional connectivities (FC) are intrinsically coupled, and this relationship declines in mild cognitive impairment (MCI). However, the underlying mechanisms of this decoupling remain unclear. Moreover, the impact of focal lesions (white matter hyperintensities, WMH) on decoupling remains unclear. Brain network communication models provide insights into this decoupling mechanism in MCI by estimating neural signal propagation along SC.

Five communication measures (CM) representing diffusion, path-accessibility, and routing-based communication strategies were derived from SC to estimate CM-FC coupling in 186 MCI and 171 cognitively normal subjects. Comparisons were conducted across groups and tractography types. Lesion mapping and mediation analyses were conducted to investigate how WMH influences cognition through coupling.

MCI subjects exhibited significant whole-brain CM-FC decoupling, prominently within the default mode, sensorimotor, and visual networks. This decoupling was driven predominantly by diffusion-based communication strategies (communicability and flow graph), whereas routing-based coupling was relatively preserved. Compared with intact-fiber networks, WMH-impaired networks showed reduced diffusion-based coupling but relatively enhanced path-accessibility-based coupling, suggesting compensatory rerouting of information flow. Lesion mapping implicated WMH in the corona radiata as critical for disrupting CM-FC coupling, and mediation analyses demonstrated that diffusion-based coupling partially mediated the association between WMH burden and memory deficits.

Our findings revealed diffusion-based CM-FC decoupling in MCI and introduced a novel framework for assessing the lesion effects of WMH. These findings provide insights into brain network dynamics and their alterations by white matter injury in MCI.