Structural Connectivity Disruption and Structural-Functional Decoupling in Working Memory Networks Across...

Area of Science:

• Neuroscience
• Nephrology
• Cognitive Science

Background:

• End-stage renal disease (ESRD) is linked to cognitive deficits, specifically working memory (WM) impairment.
• Understanding the neural underpinnings of WM dysfunction in ESRD is crucial for identifying therapeutic targets.

Purpose of the Study:

• To compare structural connectivity (SC), functional connectivity (FC), and structural-functional coupling (SFC) in pre-dialysis ESRD (ESRDp), maintenance hemodialysis ESRD (ESRDm), and healthy controls (HCs).
• To investigate the relationship between these connectivity measures, serum markers, and WM performance in different ESRD stages.

Main Methods:

• Utilized diffusion MRI and fMRI on 29 ESRDp, 29 ESRDm, and 46 HCs performing 0-, 1-, and 2-back tasks.
• Defined WM nodes using a meta-analytic map overlaid with the Harvard-Oxford atlas.
• Computed SC, FC, and regional SFC, and analyzed group differences, correlations with serum markers, and mediation effects.

Main Results:

• ESRDp demonstrated significantly lower WM accuracy, longer reaction times, reduced frontoparietal SC, and widespread SFC reductions compared to ESRDm and HCs.
• ESRDm showed near-normal WM performance with partially restored SC and SFC.
• Elevated urea and lower sodium in ESRDp correlated with weaker SC and altered SFC, which mediated poorer WM accuracy and slower reaction times.

Conclusions:

• Pre-dialysis ESRD is characterized by disrupted and decoupled WM networks.
• Maintenance hemodialysis is associated with partial normalization of WM networks in ESRD.
• Combined assessment of WM-related SC, SFC, and serum markers may identify cognitive vulnerability in ESRD.