Altered dynamic functional connectivity associated with cognition in diverse severity of white matter hyperintensity

To investigate the dynamic functional connectivity (DFC) pattern in diverse severity of white matter hyperintensity (WMH) and explore the relationship between DFC temporal properties and cognitive impairment in WMH severity.

Our study enrolled 85 CSVD patients diagnosed by the Neurology Department of the Fifth People's Hospital of Shanghai, Fudan University. All participants underwent demographic surveys, assessments of vascular risk factors, neuropsychological testing, both structural and resting-state functional MRI scans. To explore the influence of WMH severity on cognition, subjects were categorized into two groups based on their WMH Fazekas rating scale scores: (1)mild WMH group scored 1-2 (n = 55); (2)severe WMH group scored 3-6 (n = 30). We calculated DFC by using sliding window correlation approach. Subsequently, we employed k-means clustering to identify distinct DFC states and calculated DFC temporal properties (including mean dwell time, fractional windows and transition numbers).

The intrinsic brain functional connectivity of both mild and severe WMH subjects was clustered into four distinct connectivity states (state 1: intermediate pattern, state 2: a more frequent, sparsely connected pattern, state 3: intermediate pattern, state 4: a less frequent, strongly connected pattern). Compared to mild WMH group, severe WMH subjects dwelled relatively longer in hypoconnected state 2, and shorter in hyperconnected state 4. Across the whole WMH subjects, mean dwell time and fractional windows of hypoconnected state 2 showed negative exploratory correlations with executive function, whereas the corresponding metrics of hyperconnected state 4 showed positive exploratory correlations before multiple comparison correction. Additionally, transition numbers demonstrated a negative correlation with the WMH Fazekas rating scale scores.

The severity of WMH affects DFC temporal properties to a certain extent, and exploratory correlations suggest a possible link to cognition. These exploratory findings need replication in larger, multicenter cohorts before firm conclusions can be drawn.