Connectome gradient dysfunction contributes to white matter hyperintensity-related cognitive decline

Area of Science:

• Neuroimaging
• Cognitive Neuroscience
• Neurology

Background:

• White matter hyperintensity (WMH) is linked to cognitive decline, but underlying mechanisms are unclear.
• Functional brain networks exhibit a primary-to-transmodal gradient from sensation to cognition.
• It remains unknown how WMH progression alters this gradient and affects cognition.

Purpose of the Study:

• To investigate the relationship between WMH volume and functional connectome gradient structure.
• To explore how alterations in the primary-to-transmodal gradient are associated with cognitive function in WMH individuals.

Main Methods:

• Utilized resting-state functional MRI (rs-fMRI) in 758 WMH individuals.
• Reconstructed functional connectome gradients using a gradient decomposition framework.
• Analyzed associations between WMH distribution, gradient measures, and cognitive domains.

Main Results:

• Increased WMH volume correlated with poorer executive function and processing speed.
• WMH progression reduced the range and variance of the primary-to-transmodal gradient.
• A narrower gradient range and smaller variance were linked to poorer executive function.

Conclusions:

• WMH volume, primary-to-transmodal gradient, and cognition are interconnected.
• WMH negatively impacts executive function, partly mediated by reduced gradient differentiation.
• Findings highlight the role of altered brain network organization in WMH-related cognitive impairment.