Longitudinal FMRI Assessment Of Inhibitory Control In Heroin Use Disorder On Methadone Maintenance Treatment

Objective: So far,the relapse rate of heroin forced abstinence in methadone maintenance treatment(MMT)is high.There are many factors that affect relapse.Interventions of social,economic and environmental factors can eliminate physiological cravings,but the psychological craving for relapse is an insurmountable problem because the psychological and neural mechanisms are not fully understood.The current understanding of relapse-associated neural mechanisms is still insufficient.Previous studies have shown that short-term abstinent heroin addicts have strong incentives for acute drug-related clues that trigger impulsiveness and may represent a high relapse susceptibility.However,in addition to the craving,reward,and impulsive neural circuits,the relapse consciousness or behavior should also consider the contradictory aspect of the system's counteraction.The impairment of inhibitory control function in heroin abstainers may be one of the important factors of relapse.However,there are many inconsistencies in these researches,and there is a conflict between how to monitor and regulate craving,reward,impulse and inhibitory control.There are many places where further research needs to be refined.This is a longitudinal control study,heroin use disorder who were forced abstinence from MMT were recruited,3.0T magnetic resonance imaging(MRI)were used.GO-NOGO inhibitory control task and drug cues induce craving task were applicated for functional MRI(fMRI),combined with psycho-behavioral,inhibitory control task scale,craving scale and other indicators,centered around the following two issues:(1)The change rules of inhibitory control behavioral and functional brain regions at different time points in heroin abstainers under MMT;(2)How the heroin abstainers handles the conflict information between the inhibitory control and craving.Methods: Part 1: fMRI scans of GO-NOGO tasks reflecting inhibitory control functions were performed on 21 heroin abstainers who had been subjected to MMT for a long period of time.The first scan defined as S1,follow-up scan S2.Paired t-tests were used to compare brain activation between the two groups using SPM8,and correlations between the activation intensity and methadone dose were analyzed.Part 2: The same 21 heroin abstainers as experiment 1,performed another fMRI scans reflecting craving changes under heroin cueing conditions at the same time point,and paired t-tests were used for brain activation between the two groups using SPM8.Correlattions were comoared between the activation intensity rate and the methadone dose.At the same time,the brain area of part 1 was compared and analyzed.Part 3: On the basis of part 1,the data of the third time point after two years(S3)is collected.The inhibitory control behavior of 12 patients who received stable MMT at three time points(S1,S2,and S3)at 2 years were monitored.Brain activation was statistically processed by one-way ANOVA,and the correlation between the activation intensity and methadone dose was analyzed.Results: Part 1: Compared with S1,there was no significant difference in the S2 in personality scale including depression,anxiety,and impulsivity;behavioral data,including reaction time,correct rate of GO,and error rate of NOGO,were not statistically significant;Bilateral supraorbital gyrus,precentral gyrus,inferior parietal lobe,insula,left posterior middle gyrus,cuneate gyrus,supramarginal gyrus,superior frontal gyrus,tongue gyrus,right inferior frontal gyrus,middle cingulate enhancement,no negative The activation zone.The activation intensity of the left precentral gyrus and the left superior temporal gyrus was negatively correlated with the daily methadone treatment dose(r =-0.534,P = 0.013;r =-0.661,P = 0.001.respectively).Part2: Compared with S1,there was no significant difference in S2's craving score and disgust score;in the clue picture task status(clue-neutral),the right inferior frontal gyrus and superior temporal gyrus showed negative activation.There was overlap in the activation brain areas with inhibitory control tasks;the rate of change in activation intensity was not related to methadone dose.Part 3: At the three time points within two years,there were no significant difference among 3 groups' GO-NOGO test parameters of cognition and execution ability,including reaction time,correct rate of GO,and error rate of NOGO.There was positive activation in the left precentral gyrus and right postcentral gyrus,there was no correlation between the change rate in activation intensity and the use dose of methadone.Conclusions:(1)After one year of MMT for heroin abstainers,their personality metrics,including depression,anxiety,and impulsivity,were not significantly different.Behavioral aspects,including reaction time,correct rate of GO,error rate of NOGO were also not significantly different.However,fMRI data which reflecting the processing of inhibitory control of brain processing have changed,especially in brain regions associated with cognitive control functions.It was suggested that the cognitive inhibition of heroin abstainers after MMT was improved,and it was negatively correlated with the dose of methadone,which may be related to the recovery of inhibitory control after heroin withdrawal.Moreover,the activation area of the brain region associated with behavioral control was small,and the core brain region was not activated,which may explain that the patient's ultimate inhibitory behavior did not show improvement.And this reason may also be one of the psychological mechanisms of relapse in MMT patients.(2)Using the drug-induced craving task paradigm,we found that after one year of MMT in heroin abstainers,there was a negative activation in the right inferior frontal gyrus,and this brain region was also exhibited enhanced activation during inhibitory control tasks.This result may suggest that the right frontal gyrus has an important role in regulating inhibitory control function and reducing the prominence value of heroin cue induction.(3)After 2 years and three time points observed,heroin abstainers with MMT show enhanced activation in the left precentral gyrus and right postcentral gyrus,which may suggested the recover of inhibitory control function.The result may implied that MMT can maintain heroin abstainers adhere to control,reduce the impulse for various clues of drug induced,reduce relapse frequency or relapsed dose,adhere to the integrity.(4)The experimental results show that even after a relatively long-term MMT,the inhibitory control core brain regions of the heroin abstainers also difficult to appear positive activation,behavior also failed to get better.The results confirm that MMT is a long-term process of pharmacology.Therefore,at present,the intervention study of MMT for heroin users should pay attention to how to reduce the frequency or dosage of relapse,so as to maintain normal living standards and moral standards.These results are expected to provide more help for the study of the relapse mechanism of heroin users.