Alteration of gamma-aminobutyric acid in the left dorsolateral prefrontal cortex of individuals with chronic insomnia: a combined transcranial magnetic stimulation-magnetic resonance spectroscopy study

To investigate changes in the level of gamma-aminobutyric acid (GABA) in the left dorsolateral prefrontal cortex (DLPFC) of patients with chronic insomnia treated with real repetitive transcranial magnetic stimulation (rTMS) as compared to sham-rTMS, as measured with 1H-Magnetic Resonance Spectroscopy (1H-MRS). Forty chronic insomnia participants were randomized to either real or sham rTMS group. The rTMS was administered once per day Continuously for 14 days with the stimulation over the left DLPFC. Left DLPFC GABA level relative to creatine (Cr) was measured by 1H-MRS. Insomnia symptom was evaluated by Insomnia Severity Index (ISI). MRS and ISI were assessed among all participants before and after treatment. This study was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100047255). After treatment, the ISI score in real rTMS group was markedly decreased as compared to pre-rTMS (t = −4.25, p < 0.001, Cohen's d = 0.90), whereas no significant change in ISI was observed in the group of sham rTMS. In addition, we observed a significant increase of GABA+/Cr concentration in the real rTMS group after stimulation (0.37 ± 0.11 to 0.40 ± 0.11, p = 0.039), but that of sham did not (0.38 ± 0.10 to 0.39 ± 0.11, p = 0.151). However, there was no significant association between the change of GABA+/Cr in left DLPFC and the changes of ISI scores in the two groups. 1 Hz rTMS has the potential to increase GABA + level in left DLPFC of patients with chronic insomnia, and warrants further investigation.