Reduced coupling between global signal and cerebrospinal fluid inflow in patients with generalized anxiety disorder: A resting state functional MRI study.

Background: Generalized anxiety disorder (GAD) is characterized by excessive, uncontrollable worry and is associated with cognitive impairments, particularly in memory function. Recent evidence indicates that the coupling between global blood‑oxygen-level-dependent (gBOLD) signals and cerebrospinal fluid (CSF) inflow dynamics serves as a non-invasive biomarker of glymphatic function. Given the glymphatic system's critical role in metabolic waste clearance and memory consolidation-processes impaired in GAD-we investigated this coupling as a potential mechanism underlying cognitive deficits. The present study aims to investigate the coupling between gBOLD signals and CSF inflow in GAD patients compared to healthy controls (HCs).

Methods: We conducted a resting-state functional magnetic resonance imaging (rs-fMRI) study involving 116 participants, including 70 GAD patients and 46 HCs. We quantified the coupling between gBOLD signaling and CSF inflow to represent glymphatic function. Additionally, we correlated these findings with clinical measures, including the Digit Span Test (DST), which assesses cognitive memory function.

Results: Our results revealed a significant reduction in the coupling between gBOLD signals and CSF inflow in GAD patients compared to the control group. This reduction in coupling was associated with impaired performance on the DST (DST-Forward, r = 0.505, p = 0.002; DST-Backward, r = 0.581, p < 0.001).

Conclusion: Our findings suggest that reduced glymphatic function, as measured by gBOLD-CSF coupling, is associated with impaired cognitive function in GAD patients. This association may reflect a potential neurobiological link between glymphatic dysfunction and cognitive deficits in GAD.