Navigated and individual [alpha]-peak-frequency-guided transcranial magnetic stimulation in male patients with t aper

Background: Previous electroencephalography (EEG) studies have indicated altered brain oscillatory [alpha]-band activity in schizophrenia, and treatment with repetitive transcranial magnetic stimulation (rTMS) using individualized [alpha]-frequency has shown therapeutic effects. Magnetic resonance imaging-based neuronavigation methods allow stimulation of a specific cortical region and improve targeting of rTMS; therefore, we sought to study the efficacy of navigated, individual [alpha]-peak-frequency-guided rTMS ([alpha]TMS) on treatment-refractory schizophrenia. Methods: We recruited medication-refractory male patients with schizophrenia or schizoaffective disorder in this double-blind, sham-controlled study. We randomized patients to a 3-week course of either active [alpha]TMS or sham stimulation applied to the left dorsolateral prefrontal cortex (DLPFC). We assessed participants with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale (CGI) at baseline and after treatment. We conducted a follow-up assessment with the PANSS 3 months after intervention. Results: We included 44 patients. After treatment, we observed a significantly lower PANSS total score (p = 0.029), PANSS general psychopathology score (p = 0.027) and PANSS 5-factor model cognitive-disorganized factor score (p = 0.011) in the [alpha]TMS group than the sham group. In addition, the CGI-Improvement score was significantly higher among those who received [alpha]TMS compared with sham stimulation (p = 0.048). Limitations: The limited number of study participants included only male patients. Depression was not formally evaluated. Conclusion: Navigated [alpha]TMS to the left DLPFC reduced total, general psychopathological, and cognitive-disorganized symptoms of schizophrenia. These results provide evidence for the therapeutic efficacy of individual [alpha]-peak-frequency-guided rTMS in treatment-refractory schizophrenia. Clinical trial registration: NCT01941251; ClinicalTrials.gov