Reduced coupling between global brain activity and cerebrospinal fluid flow in middle-aged and older adults with chronic insomnia: enhancement by low-frequency rTMS

This study demonstrates that middle-aged and older adults with chronic insomnia show reduced global blood oxygenation level-dependent (gBOLD)-cerebrospinal fluid (CSF) coupling, indicating alterations in CSF-related dynamics that may reflect glymphatic-relevant processes at the cortical functional level. These alterations were most pronounced in high-order brain networks and were associated with poorer sleep quality. Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) applied to the right dorsolateral prefrontal cortex modulated gBOLD-CSF coupling and improved sleep symptoms, with benefits maintained at 12 months. These findings suggest that disrupted CSF-dynamics coupling may be a functional marker associated with chronic insomnia in later adulthood and support LF-rTMS as a feasible non-pharmacological approach for long-term management, potentially enabling targeted modulation of CSF-dynamics-related processes.