Reduced BOLD-CSF coupling as a potential functional imaging correlate of semantic fluency decline in MRI-negative...

This study investigated neurovascular-cerebrospinal fluid dynamic interactions using blood-oxygen-level-dependent-cerebrospinal fluid (BOLD-CSF) coupling metrics and examined their associations with cognitive impairment in patients with MRI-negative unilateral temporal lobe epilepsy (TLE).

In this retrospective study, 36 patients with MRI-negative unilateral TLE and 26 healthy controls (HCs) recruited during the same study period were enrolled. Resting-state functional MRI (rs-fMRI) was used to quantify global BOLD-CSF (gBOLD-CSF) and temporal BOLD-CSF (tBOLD-CSF) coupling. Comprehensive neuropsychological assessments included the Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), Digit Span Test (DST), Block Design, Phonological Fluency Test (PFT), and semantic verbal fluency (SVF). Partial correlations and multivariable linear regression were performed to evaluate associations between imaging metrics and cognitive performance.

Compared with HCs, TLE patients showed significantly poorer performance on MoCA (p = 0.007), DSST, DST, Block Design, PFT, and SVF (all p < 0.001). Both gBOLD-CSF and tBOLD-CSF coupling strengths were markedly reduced in TLE patients (FDR-p < 0.001 for both). After adjustment for age, sex, education level, and sleep duration, both coupling metrics were positively associated with SVF performance. False discovery rate (FDR) correction was applied to the three prespecified primary imaging-SVF associations-gBOLD-CSF coupling, tBOLD-CSF coupling, and CPV-using the Benjamini-Hochberg procedure. The associations between the BOLD-CSF coupling metrics and SVF performance remained significant after FDR correction (gBOLD-CSF coupling: partial r = 0.723, unadjusted p < 0.001, FDR-adjusted p < 0.001; tBOLD-CSF coupling: partial r = 0.396, unadjusted p = 0.025, FDR-adjusted p = 0.038).

Reduced tBOLD-CSF and gBOLD-CSF coupling may serve as functional imaging correlates of semantic network vulnerability in patients with MRI-negative TLE.