The Study Of Event Related Potentials In The Treatment Of Drug Addiction By Deep Brain Stimulation

Background and objective:Drug dependence has the refractory characteristic and high relapse rate.In recent years,with the deepening understanding of the dangers of drug abuse,addiction has become a serious social problem.Currently the most common treatment methods including drug replacement therapy,psychological behavior therapy and traditional Chinese medicine therapy can not effectively reduce the relapse rate of addicts.The most important reason why addicts can not maintain long-term abstinence is the addicts can not complete withdrawal the psychological dependence.Although the addicts have been aware of the drug’s harm on themselves,their families,and society,they still can not control to use the drugs.With the increasing dose of drug use,they are gradual tolerance,Therefore,the key point of the current research is how to withdraw craving.At the end of 1990 s,our center had explored the therapeutic effect of nucleus accumbens ablation on the treatment of addiction.We conducted a multicenter follow-up of 150 patients in 2004,28 cases of addicts lost to follow-up,75 cases of addicts without relapse,and the 5 years abstinence rate was up to 61.5%,however,the relapse rate of addicts without surgery was up to 97%,this outcomes confirmed the effectiveness of ablation on treatment of drug addiction.But the complications of the ablation were more severe,which limited its follow study.In 2009,our center began the study of deep brain stimulation(DBS)in the treatment of addiction.At present,DBS detoxification is mainly based on self-reported craving and relapse rate,it is an obstacle to the further study of DBS because of the lack of more objective evaluation methods.The event related potential(ERP)can observe the dynamic changes of addicts cognition and craving because its high time resolution and noninvasive features.It has important value on the addiction prevention,treatment and relapse prevention,but whether ERP can more objectively evaluate the therapeutic effect of DBS has not been studied.Methods:Our center included 7 patients with opioid addiction met the diagnosis criterion of DSM-V,and 7 healthy volunteers from January 2015 to March 2016.The event-related potentials were recorded and analyzed respectively before operation,6 months after DBS to evaluate the changes of psychological cognition and craving in patients before and 6 months after operation,thereby to explain the effect of DBS detoxification.The event related potentials elicited by stimulation tasks including: classic oddball mode of digital P300,and the drug cue and emotional picture system which was combined with the native and foreign famous professor’s emotional picture system and Chinese affective picture system(CAPS)and the international affective picture system(IAPS).This study was a single center,prospective,controlled clinical study,which was approved by the ethics committee of Tangdu hospital(No.201510-018)and was registered on the Clinicaltrails.gov(NCT02594306).Results:The P300 amplitude of addictive patients before surgery was significantly lower than the normal control group,especially on the F3,F1,FZ,F2,FT7,FC5,FC3,FC1,FCZ,FC2,FC4,FC6,T7,C5,C3,C1,CZ,C2,C4,C6,TP7,CP5,CP3,CP1,CPZ CP2,CP4,CP6,P5,P3,P1,PZ,P2,P4,PO3,POZ leads compared with the control group,and the difference was significant(P<0.05).While patients 6 months after the DBS compared with the control group,the P300 amplitude on FT7,FC5,T7,C5,TP7 leads were lower than the control group,and the difference was significant(P<0.05),while the other leads were no difference compared with the control group.The P300 amplitude of the patients 6 months after DBS on PZ,CP1,CPZ,P1,P3,P2 leads were significantly higher than the preoperative group(P<0.05),and the difference was significant.The P300 latency of three groups was 370 to 380 milliseconds,the average reaction time were 310 to 330 milliseconds,and the correct rate was above 99%,the difference between the three groups was not significant.The early stage LPP components was found when the addiction patients received the drug cue pictures,the patients LPP amplitude of the F1,FZ,F2,FC3,FC1,FCZ,FC2,C3,C1,CZ,C2,CP1,CPZ leads were increasing,compared with the control group had statistical difference(P<0.05),and the leads were concentrated in the midline of frontal and parietal.The later stage LPP components was found when the addiction patients received neutral pictures compared with the control group,the T8 lead was higher than the control group(3.84±0.95 vs 0.99±1.39),the difference was significant(P=0.008),when they received the drug cue pictures,the LPP amplitude on C5,C3,C4,CP3,CP1,CPZ,CP2,P2,P6 leads were significantly higher than the control group,and the leads were concentrated on the side of the parietal lobe.In patients with addiction 6 months after DBS,compared with the control group,the early stage LPP components were found that they received the drug cue pictures,the LPP amplitude on CZ,C2,C4,CP3,CP1,CPZ,CP4,P1,PZ leads were higher than the control group,which located in the midline of the brain.The later stage LPP components were found when the addiction patients received drug cue pictures,the LPP amplitude on C3,C4,CP3,CP1,CPZ,CP2,P2,P6 leads were higher than the control group,the difference was significant(P<0.05),which located in the midline and both side of parietal.In addicts 6 months after DBS,compared with the preoperative patients,early stage LPP components were found when they received the positive pictures,the average amplitude on the FP1,FPZ,TP7,P5 leads decreased(P<0.05),the other leads were no significant differences.When they received the negative,neutral,drug cue pictures,All the leads were no significant difference.The later stage LPP components were found when the subjects received the positive pictures,except PO5(P=0.005),there were no significant differences on the other leads.When they received the negative pictures,except TP8(P=0.018),there were no significant differences.When they received the neutral pictures and drug cue pictures,there was no significant difference in all leads.Conclusions:The P300 amplitude of addiction decreased compared with the control group,while the DBS can effectively improve the addictive patients’ P300 amplitude,so the DBS can improve the cognitive level of addictive patients.The LPP amplitude of addictive patients preoperative were significantly higher than the control group in midline of brain,when they received the DBS treatment 6 month,the LPP amplitude were still higher than the control group.When comparing the DBS group with the preoperative group,there were no statistical improvement,but we can observe later stage LPP amplitude decreased on the midline of brain from the EEG,as a result how to prove the DBS could effectiveness decrease the LPP still need longer follow-up results.