Enhancement of glymphatic function and cognition in chronic insomnia using low-frequency rTMS

Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) is a promising treatment for chronic insomnia; however, its effectiveness in improving cognitive and glymphatic clearance functions remains unclear. We aimed to investigate the effects of chronic insomnia on glymphatic clearance function and the effectiveness of LF-rTMS on chronic insomnia.

Thirty-two patients with chronic insomnia and 40 healthy controls underwent baseline assessments of clinical measures and glymphatic functions using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS). Thereafter, 22 patients underwent 10 sessions of LF-rTMS over two consecutive weeks, sleep assessments at week 2 and months 1, 2, and 3, and DTI-ALPS and cognitive-related assessments at week 2 and month 3.

Compared to healthy controls, patients showed significant differences in the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Montreal Cognitive Assessment (MoCA) Scale, digit symbol substitution test (DSST), color trail test (CTT), digit span test (DST), Stroop tests, and DTI-ALPS index (all ps < 0.05). After LF-rTMS, patients showed a significant decrease in PSQI and ISI scores from week 2 onwards and significant improvement in MoCA, DSST, DST, CTT-B tests, and DTI-ALPS index by month 3 (all ps < 0.05). Furthermore, the increase in the DTI-ALPS index was significantly associated with improvements in PSQI, ISI, MoCA, and DST-backward at month 3 (r = 0.579, 0.558, 0.836, and 0.642, respectively, and p = 0.038, 0.047, <0.001, and 0.018, respectively).

This study provided preliminary evidence for LF-rTMS' valuable effects on glymphatic clearance and cognitive function in patients with chronic insomnia, which supports LF-rTMS' clinical application in those population.

This study has been officially registered with the Chinese Clinical Trial Registry. The trial, titled "Effect of Repetitive Transcranial Magnetic Stimulation for the Treatment of Chronic Insomnia and the Underlying Brain Mechanism," is accessible via the following URL: https://www.chictr.org.cn/showproj.html?proj=205347. The registration number assigned to this trial is ChiCTR2300077939.