Objective: Generalized anxiety disorder (GAD) is a common neuropsychiatric disorder with reduced left dorsolateral prefrontal cortex (DLPFC) activity. Transcranial near-infrared stimulation (tNIRS) can increase cerebral cortex activity. Transcranial magnetic stimulation with electroencephalography (TMS-EEG) was used to assess the effect of tNIRS treatment on time-varying EEG brain networks. 

Methods: We performed a double-blind, randomized controlled trial to evaluate the efficacy of tNIRS on the left DLPFC in patients with GAD. 36 Patients with GAD were randomly selected and divided into two groups: one group received active tNIRS and the other received sham stimulation for two weeks. Clinical efficacy was evaluated before, after, and at the 2-, 4-, and 8-week follow-ups. Twenty minutes TMS-EEG were performed before and immediately after tNIRS treatment, and healthy controls were collected only once. 

Results: After treatment, the Hamilton Anxiety Scale (HAMA) scores was more reduced in the active than sham stimulation group and the difference was statistically significant (p=0.021). The HAMA scores of the active stimulation group posttreatment and at the 2-, 4-, and 8-week follow-up were 11.50 (p<0.001), 12.64 (p<0.001), 14.30 ( p<0.001), and 14.24 ( p<0.001) points lower than those before treatment, respectively. Hamilton Depression Scale score decreased significantly after active treatment and remained stable during the eight-week follow-up, but the difference of the active stimulation group and the sham stimulation group was not statistically significant (p>0.05). The difference of Pittsburgh sleep quality index scores between the active group and sham group was not statistically significant (p>0.05). Compared with before treatment, after active treatment, TMS-EEG targeting left DLPFC of patients can induce