Abstract
Generalized Anxiety Disorder (GAD) is a highly prevalent yet poorly understood chronic mental disorder. Previous studies have associated GAD with excessive activation of the right dorsolateral prefrontal cortex (DLPFC). This study aimed to investigate the effect of low-frequency repetitive transcranial magnetic stimulation (repetitive TMS, rTMS) targeting the right DLPFC on clinical symptoms and TMS-evoked time-varying brain network connectivity in patients with GAD. Eleven patients with GAD received 1 Hz rTMS treatment targeting the right DLPFC for 10 days. The severity of the clinical symptoms was evaluated using the Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) at baseline, right after treatment, and at the one-month follow-up. Co-registration of single-pulse TMS (targeting the right DLPFC) and electroencephalography (TMS-EEG) was performed pre- and post-treatment in these patients and 11 healthy controls. Time-varying brain network connectivity was analyzed using the adaptive directed transfer function. The scores of HAMA and HAMD significantly decreased after low-frequency rTMS treatment, and these improvements in ratings remained at the one-month follow-up. Analyses of the time-varying EEG network in the healthy controls showed a continuous weakened connection information outflow in the left frontal and mid-temporal regions. Compared with the healthy controls, the patients with GAD showed weakened connection information outflow in the left frontal pole and the posterior temporal pole at baseline. After 10-day rTMS treatment, the network patterns showed weakened connection information outflow in the left frontal and temporal regions. The time-varying EEG network changes induced by TMS perturbation targeting right DLPFC in patients with GAD were characterized by insufficient information outflow in the left frontal and temporal regions. Low-frequency rTMS targeting the right DLPFC reversed these abnormalities and improved the clinical symptoms of GAD.
Highlights
Generalized anxiety disorder (GAD) is a common and debilitating mental disorder; its prevalence rate was found to be 5.7% in an epidemiological survey [1, 2]
In the present study, we found that low-frequency Repetitive TMS (rTMS) stimulating the right DLPFC was effective at improving the symptoms of GAD, and the abnormal time-varying EEG networks in GAD showed a trend toward normalization after rTMS treatment
This study demonstrates that rTMS does have potential as an effective augmentative treatment in GAD
Summary
Generalized anxiety disorder (GAD) is a common and debilitating mental disorder; its prevalence rate was found to be 5.7% in an epidemiological survey [1, 2]. The treatment of GAD is still based on drug therapy, supplemented by psychological counseling [5,6,7]; the side effects, for instance, delayed movement or dizziness, often lead to treatment cessation [8]. Despite the many drug options available, almost 40% of patients with GAD do not respond to pharmacologic treatment [9]. Transcranial magnetic stimulation (TMS) is a noninvasive, effective brain stimulation technique that can activate cortical neurons; and its principle is based on Faraday’s electromagnetic induction theory [10, 11]. RTMS has been successfully applied in the treatment of anxiety, depression, epilepsy, stroke, and other neurological and psychotic disorders [14,15,16,17,18,19,20] Repetitive TMS (rTMS) can reduce or increase cortical excitability depending on the stimulation frequency [12]: low-frequency rTMS (≤1HZ) can reduce the excitability of the motor cortex while high-frequency rTMS (≥5HZ) can excite the adjacent cerebral cortex [13]. rTMS has been successfully applied in the treatment of anxiety, depression, epilepsy, stroke, and other neurological and psychotic disorders [14,15,16,17,18,19,20]
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