Transcranial direct current stimulation improves reduced global BOLD-CSF coupling in patients with insomnia disorder and comorbid anxiety: a resting-state functional MRI study

BACKGROUND: Insomnia disorder with comorbid anxiety is a prevalent clinical challenge. Although transcranial direct current stimulation (tDCS) is a promising noninvasive neuromodulatory approach, its effects on glymphatic-related neurovascular-cerebrospinal fluid (CSF) coupling in insomnia remain unclear. This study investigated the effects of tDCS on global blood oxygen level-dependent (gBOLD)-CSF coupling using resting-state functional magnetic resonance imaging (rs-fMRI) in patients with insomnia disorder and comorbid anxiety. METHODS: We conducted a 2-week, double-blind, randomized, sham-controlled trial. Patients with insomnia disorder and comorbid anxiety were randomized to receive either active or sham tDCS. The intervention consisted of 14 consecutive daily 20-min sessions delivered at 1.1 mA, targeting the left forehead and right dorsolateral prefrontal cortex. Healthy controls were frequency-matched to the overall patient cohort by age and sex. The Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), 14-item Hamilton Anxiety Rating Scale (HAMA-14), 17-item Hamilton Depression Rating Scale, Epworth Sleepiness Scale, 20-item Multidimensional Fatigue Inventory, polysomnography (PSG), and rs-fMRI were assessed at baseline, and patients were reassessed after treatment. The primary outcome was the post-intervention between-group difference in gBOLD-CSF coupling; clinical scales and PSG parameters were secondary outcomes. RESULTS: = 0.014). Adverse events were mild and comparable between groups. CONCLUSIONS: Patients with insomnia disorder and comorbid anxiety showed reduced gBOLD-CSF coupling during wakeful rs-fMRI, which was associated with subjective sleep quality, insomnia severity, anxiety level, arousal index, and N3 sleep duration. Active tDCS enhanced gBOLD-CSF coupling compared with sham stimulation, suggesting that its therapeutic effects may involve modulation of neurovascular-CSF dynamics alongside improvements in sleep and anxiety symptoms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID NCT07340268, retrospectively registered on January, 13, 2026.