| Objectives:Methamphetamine use disorder and heroin use disorder is a chronic,relapsing disorder with few effective treatments.Repetitive transcranial stimulation（rTMS）is a non-invasive brain stimulation tool that has been increasingly used by researchers in recent years as a possible therapeutic intervention for drug use disorder.rTMS is a safe and economical way to induce neural changes in the brain that can induce neuroplasticity in the abnormal brain circuits and networks of addicts.The thesis explores the effective parameters and mechanisms of rTMS in the treatment of different types of addiction.Specifically,the effect of high/low frequency and theta burst stimulation rTMS on the treatment of methamphetamine and heroin use disorders are reflected by the improvement of craving,impulsivity,or emotional state,thus providing more references for addiction treatment programs.Finally,we explored the plasticity of the cerebral cortex in methamphetamine and heroin use disorders using TMS-EEG,thereby offering a new biomarker for the treatment of patients.Methods:In study one and experiment 1,169 methamphetamine patients and 92 heroin patients were recruited and randomly assigned into three groups,respectively.Methamphetamine patient group:69 patients with 10 Hz,50 patients with 1 Hz and 50patients with control group.Heroin patient group:34 patients with 10 Hz,27 patients with 1 Hz and 31 patients in the control group.Treatment group received rTMS treatment for 4 weeks,5 times a week;while the control group received no rTMS treatment.The basic information（age,intake years,every time usage and monthly usage）and craving scores to cue-induced were collected at four time points:the day before the treatment（day 1）,the first day after treatment（day 30）,30th day after treatment（day 60）and 60th day after treatment（day 90）.In experiment 2,29methamphetamine patients and 29 healthy controls were recruited.Participants in the experimental group received 10 Hz TMS therapy 5 times a week for 4 weeks.The stimulation site was left DLPFC;while the control group received no rTMS treatment.The basic information（gender,age,intake years,every time usage and monthly usage）and craving scores to cue-induced were collected and the stop-signal task&No Go was used to measuring impulsivity before and after treatment,the information of the healthy controls’gender and age was collected at the same time and the stop-signal task&No Go was used to measuring impulsivity.The differences in impulsivity between the control group and the methamphetamine patients before and after treatment were compared.In study two,20 methamphetamine patients were recruited and randomly assigned into two groups in experiment 3:intermittent theta burst stimulation（iTBS）group and10 Hz group.They were treated five times a week for the first two weeks and once a week for the next two weeks,with the stimulation site at the left DLPFC.The basic information（age,intake years,every time usage and monthly usage）were collected before TMS treatment.Craving scores to cue-induced,anxiety scores,depression scores and withdrawal scores were collected at four time points:the day before the treatment（baseline）,after two weeks treatment（day 10）,upon a week after treatment（day 15）and upon another week after treatment（day 20）.In experiment 4,32 methamphetamine patients were recruited and randomly assigned into 3 groups:virtual reality（VR）-10minutes interval-continuous theta burst stimulation（c TBS）group,the VR-6 hours interval-c TBS group and VR-10 minutes interval-sham c TBS group,each group of11,11 and 10 participants.The participants received 10 Hz TMS therapy for 2 times at left DLPFC.The basic information（age,intake years,every time usage and monthly usage）were collected before treatment.Craving scores and possibility of using methamphetamine to cue-induced,anxiety scores,depression scores,withdrawal scores and impulsivity were collected before and after treatment.In study three and experiment 5,baseline single-pulse TMS was delivered to 3cortical sites（F3,F4,and P3）.Following the baseline measures,a single-session of rTMS was delivered.Finally,single-pulse TMS was repeated to the 3 stimulation sites in order to measure change elicited by the rTMS intervention on 73 heroin and 69methamphetamine patients,as well as 35 healthy controls.Results:In study one,experiment 1 found that:（1）High frequency and low frequency rTMS stimulation of the left DLPFC significantly reduced the cue-induced craving of methamphetamine patients and heroin patients,and the treatment effect could be maintained 60 days after the end of treatment.（2）The delta craving at day 30 predicted the change of craving at day 60 and at day 90.Experiment 2 found that:（1）high frequency rTMS stimulation of left DLPFC decreased cue-evoked craving for methamphetamine patients.（2）The impulsivity of the experimental group was significantly higher than control group before treatment,but there was no difference between the two groups after treatment.In study two,experiment 3 found that iTBS and high frequency rTMS stimulation of left DLPFC could reduce cue induced craving and withdrawal symptoms of methamphetamine patients,and there was no significant difference in treatment effect of the two treatment modes.Experiment 4 found that VR-c TBS significantly reduced cue-elicited craving and possibility of using scores in methamphetamine patients.In study three,experiment 5 found that there were no significant differences between the three groups at baseline,but during P3 stimulation,the heroin patients showed significantly decreased Alpha power globally compared to healthy controls in the time window from 43-139 ms post stimulation.During F4stimulation,there was a significant increase in Alpha power in the left temporal region in the heroin group,which was not seen in the other two groups.During P3 stimulation,there was a significant decrease in Alpha power globally in the control group from 43-139 ms,whereas there was a significant increase in Alpha power for the heroin patients within the same time window.We saw an increase in Beta power for the healthy control group during F3 stimulation.During F4 stimulation,there was a decrease in Beta power for the healthy control group in the right frontal,parietal and temporal regions.Conclusions:High frequency and low frequency rTMS stimulates left DLPFC,which can not only reduce the cue-induced craving of methamphetamine patients,but also decrease the cue-evoked craving of heroin patients.High frequency rTMS stimulates left DLPFC,which can not only reduce the cue-induced craving of methamphetamine patients,but also reduce their impulsiveness and improve their inhibitory control ability.Compared with high frequency rTMS,iTBS can also effectively reduce the cue-evoked craving and withdrawal symptoms of methamphetamine patients.VR-c TBS can efficiently reduce the cue-induced craving of methamphetamine patients.TMS-EEG can probe cortical plasticity in heroin and methamphetamine patients.Differences between the two drug classes（and compared to healthy individuals）can be used to inform and enhance treatment selectively for each patient subtype.In summary,rTMS can effectively treat substance addiction,but the specific mechanism still needs to be explored. |
