Astudy Of The Therapeutic Effect And Its Neural Mechanism Of Repetitive Transcranial Magnetic Stimulation In Patients With Disorders Of Consciousness

Background and ObjectiveDisorders of consciousness(DoC)are a series of arousal and cognitive disorders secondary to severe brain injury,5-10%of them fail to regain consciousness from coma(usually 2-4 weeks),ranging from vegetative state/unresponsive wakefulness syndrome(VS/UWS)and minimally conscious state(MCS),its bring a great challenge to clinical diagnosis and treatment Recently,repetitive transcranial magnetic stimulation(rTMS)has been widely used in patients with DoC.However,its effectiveness is not satisfactory(30～36).The most important reason is that the stimulation target of rTMS in DoC patients is difficult to determine.Therefore,by conducting crossover randomized controlled trials,according to the global workspace theory and integrated information theory of DoC neural mechanism as the theoretical support,this study combined behavioral and related neuro-electrophysiology indicators as outcomes to evaluate the effect of the left posterior parietal cortex(PPC)and the dorsal lateral prefrontal cortex(DLPFC)of rTMS on improving the awareness level of VS/UWS and MCS patients.MethodsTwenty VS/UWS patients were enrolled in trial 1 and thirteen MCS patients were enrolled in trial 2.We aim to evaluate the efficacy and safety of using 10 Hz rTMS over the posterior parietal cortex(PPC)in VS/UWS patients and the left dorsal lateral prefrontal cortex(DLPFC)in MCS patients,respectively.Patients of both two trials were randomly divided into two groups in a 1:1 ratio and received 10 sessions of intervention with 10 Hz rTMS-active and 10 sessions of rTMS-sham.Ten days’ washout period was set between active and sham treatment.Coma Recovery Scale-Revised(CRS-R)was used as the primary outcome.The relative power spectral density was used as the secondary outcome in trial 1.The relative power spectral density,TMS evoked potential and Global Mean Field Amplitude as measured by TMS-EEG were used as the the secondary outcomes in trial 2.ResultsTrial 1 Compared to the rTMS-sham treatment,the rTMS-active treatment exhibited a significant improvement in CRS-R total scores(F=8.443,P=0.009)and alpha relative power of the whole brain(F=11.166,P=0.004)in VS/UWS patients.Furthermore,eight patients gained new signs of consciousness as MCS following rTMS-active and were defined as rTMS responders.Compared with rTMS-sham,rTMS-active significantly improved the CRS-R score in VS/UWS patients(F=9.135,P=0.029)in rTMS responders at the group level,while non-responders had no significant improvement.Trial 2 Compared to the rTMS-sham treatment,the rTMS-active treatment exhibited a significant improvement in CRS-R total scores(F=5.241,P=0.043),relative a power of the whole brain(F=9.717,P=0.010),the amplitude of the TMS evoked potential at N45(F=6.307,P=0.029)and the Global Mean Field Amplitude at N180(F=11.285,P=0.010)in MCS patients.Furthermore,seven patients gained new signs of consciousness following rTMS-active and were defined as rTMS responders.Compared with rTMS-sham,rTMS-active significantly improved the CRS-R score of MCS patients(F=6.963,P=0.046)in rTMS responders at the group level,while non-responders had no significant improvement.There were no adverse events associated with the study.Conclusions(1)Compared with rTMS-sham,10 Hz rTMS over the left PPC significantly improved functional recovery and relative a power in VS/UWS patients.(2)Compared with rTMS-sham,10 Hz rTMS over the left DLPFC significantly improved functional recovery and relative a power in MCS patients.(3)In both VS/UWS and MCS patients,the improvement of relative alpha power in the resting EEG background is a possiblely necessary objective condition for improving/restoring consciousness.