Using Repetitive Transcranial Magnetic Stimulation to Improve the Auditory Mismatch Negativity Deficits of Schizophrenia: a Randomized, Double-blinded, Sham-controlled Clinical Trial

Auditory mismatch negativity deficit is a robust neurophysiological biomarker of schizophrenia. Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulation method and can be used to modulate excitability of specific brain cortical region. We hypothesize that MMN deficit of schizophrenia is related to inferior frontal gyrus (IFG) hypofunction, and this deficit can be improved by using rTMS to enhance IFG function. It is a randomized, double-blinded, sham-controlled clinical trial. Forty-eight schizophrenia patients with MMN deficits (mean amplitude at FCz > -0.7 ㎶) will be recruited and then randomized at a 1:1 ratio to rTMS group and sham-stimulation group. Subjects in rTMS group will receive high frequency rTMS over IFG, while in the other group subjects will receive sham stimulation at IFG. Frameless stereotaxy navigation will be used to guide the rTMS coil to IFG. The primary outcome is the change of MMN mean amplitude at FCz after stimulation. We hypothesize that the change of MMN mean amplitude is significantly larger in rTMS group than in sham-stimulation group. Their cognitive function and clinical condition will be evaluated carefully before and after experiments.