Effect Of Low-Frequency Repetitive Transcranial Magnetic Stimulation On Response Inhibition And Craving With Methamphetamine Dependences

According to the data of China drug forms in 2018,the population of methamphetamine(MA)users has been growing every year,with MA users accounting for 55% of the total drug users in China.MA dependence can cause some problems such as impaired response inhibition ability,high impulsivity,and violent aggression.However,there is still a lack of effective treatment with MA dependents.Response inhibition ability with MA dependence has significantly impairment,the impaired inhibition ability may be an important reason for MA dependence drug relapse.At the same time,one study has shown that restoring behavioral control and reducing impulsivity is a key step for abstinence with MA dependence.Repetitive Transcranial Magnetic Stimulation(rTMS)stimulates the brain by applying different frequencies to different parts of the cortex to regulate neural activity.In general,low-frequency rTMS can reduce excitability and impulsivity,while high-frequency rTMS can increase excitability,and has been demonstrated in the nicotine,alcohol,cocaine,and other dependence groups.Therefore,in Study 1,the Two-choice Oddball task was used to explore the response inhibition ability of 1 Hz rTMS on the response inhibition ability of MA dependence.The Two-choice Oddball task requires the subjects to make different keystroke responses as accurately and quickly as possible for both the short-time presented standard stimulus W(high frequency)and deviant stimulus M(low frequency).All the MA dependence completed the Two-choice Oddball task twice a day,namely the pretest and post-test of the behavioral experiment.The experimental process of study 1 was as follows: MA dependence completed the pre-test of the behavior experiment and received the corresponding rTMS intervention at an interval of 5 minutes,and then received the post-test of the behavior experiment at an interval of 5 minutes.The key indexes of response inhibition were the accuracy of deviant stimulus and the delayed response time(deviant stimulus reaction time-standard stimulus reaction time)of the Two-choice Oddball task.The higher the accuracy of deviant stimulus,the higher the value of delayed reaction time,the better the response inhibition ability of the subjects.MA cravings were measured by the subjective rating of the five-minute video cues,with the higher the score,the more MA cravings.In study 1,45 male MA dependents(23 in the 1 Hz rTMS group and 22 in the Sham rTMS group)were recruited from a drug rehabilitation center in Jiangsu Province.All MA dependence met the criteria of the Diagnostic and Statistical Manual of Mental Disorders(5th Edition)(DSM-Ⅴ)for amphetamine-type stimulant dependents.There were no significant differences in age,education level,smoking,and alcohol consumption between the healthy group and the MA group.The left Dorsolateral prefrontal cortex(DLPFC)was stimulated in the MA group.The rTMS stimulation in the Sham group did not affect the cerebral cortex of the MA dependents,and other setting parameters were the same as those in the 1 Hz rTMS group.the study showed that the accuracy of deviant stimulus and delayed reaction time were significantly improved in the 1 Hz rTMS group compared with the Sham rTMS group,and there was no significant difference in the performance of behavior post-test in the 1 Hz rTMS group compared with the healthy group.These results indicate that 1 Hz rTMS has a significant promoting effect on the response inhibition ability of MA dependents.In study 1,we found that 1Hz rTMS treatment of left DLPFC could significantly improve the response inhibition ability of MA dependents,but we were unable to determine whether the improvement of response inhibition ability could reduce the drug craving of MA dependents,and whether the promotion effect was sustainable.Therefore,Study 2 further explored the intervention effect of 1Hz rTMS on MA dependents,and directly measured the response inhibition ability and addiction index——MA craving degree of MA dependence after receiving 1Hz rTMS.MA dependents were tested pre and post the first behavioral test,retested after 10 consecutive days of intervention,and followed up at intervals of 20 days.The healthy subjects served as controls were identical to those in study 1.In study 2,73 male MA addicts(37 in the 1 Hz rTMS group and 36 in the SHAM rTMS group)who had not participated in study 1 were recruited in a drug rehabilitation center in Jiangsu Province.All MA dependents met the criteria of the Diagnostic and Statistical Manual of Mental Disorders(5th Edition)(DSM-Ⅴ)for amphetamine-type stimulant addicts.Results of study 2 replicated the effect of study 1 on response inhibition in MA dependents with 1 Hz rTMS.In addition,there was a significant correlation between the cost of pretest accuracy(the accuracy of standard stimulus-the accuracy of deviation stimulus)and the craving score.After 1 Hz rTMS intervention,there was a significant positive correlation between the cost of pretest accuracy and the change of response inhibition ability(the cost of pretest accuracy-the cost of posttest accuracy).pretest accuracy cost and the change of craving(pretest craving-post craving)has shown in significantly positive correlation,This indicates that the worse the response inhibition ability of Ma addicts intervened by 1 Hz rTMS,the greater the inhibition effect on their response inhibition ability and drug craving,and this inhibition effect may be promoted by the enhancement of response inhibition ability.More importantly,the retest results after 10 consecutive days of intervention and 20 days intervals were still stable.In conclusion,the results of the two studies jointly reveal that low-frequency 1Hz rTMS can promote the improvement of LDLPFC’s response inhibition ability and the reduction of drug craving in MA addicts.Moreover,the effect of 1 Hz rTMS on the craving of MA addicts was influenced by the improvement of their response inhibition ability.