Cognitive Compensation Depends on Frontoparietal Network Structure-Function Coupling in Patients With White Matter...

White matter hyperintensity (WMH) impairs cognitive function but is not evident in the early stage, raising the need to explore the underlying mechanism. We aimed to investigate the potential role of network structure-function coupling (SC-FC coupling) in cognitive performance of WMH patients.

A total of 617 participants with WMH (mean age = 61 [SD = 8]; 287 females [46.5%]) were retrospectively included from the Cognitive Impairment, Retinopathy, and Cerebrovascular Lesions in the Elderly (CIRCLE) study who underwent multimodal MRI and comprehensive cognitive assessments. Severe WMH was defined as periventricular WMH with a Fazekas score of 3 and/or deep WMH with Fazekas score ≥ 2; otherwise it was defined as mild WMH. The network SC-FC coupling was derived from diffusion tensor imaging and functional MRI.

Across networks, the frontoparietal network exhibited the lowest SC-FC coupling, while the somatomotor network was the highest. Within the mild WMH subgroup, only frontoparietal network SC-FC coupling was positively correlated with WMH volume (β = 0.136, p = 0.014), a pattern not observed in the whole cohort and the severe WMH subgroup (all p > 0.05). Furthermore, in the mild WMH subgroup, frontoparietal network SC-FC coupling was also positively correlated with cognitive performance on the digit span forward task, both in cross-sectional (β = 0.110, p = 0.023) and longitudinal analyses (β = 0.245, p = 0.038).

Overall, the frontoparietal network SC-FC coupling may contribute to cognitive compensation during the mild stage of WMH and could be a target for interventions aimed at preserving cognitive abilities.