The Effect And Neuroimaging Mechanism Of Repetitive Transcranial Magnetic Stimulation On Heroin-dependent Individuals

Background Heroin dependence is a serious substance use disorder that poses a serious threat to public health and social stability.It is particularly important to explore the mechanisms and intervention methods of heroin dependence.The abnormal interactions of 3 key largescale brain networks [default mode network(DMN),salience network(SN)and executive control network(ECN)] were shown underlie dysfunctions in heroin dependence.Repetitive transcranial magnetic stimulation(r TMS)has been identified as a potential intervention for substance dependence.However,there are few studies on r TMS in the intervention of heroin dependence,and its mechanism of intervention is still unclear.Functional magnetic resonance imaging(f MRI)studies based on large-scale brain networks help reveal the neural mechanisms of r TMS intervention in heroin dependence.ObjectiveTo investigate the effect of r TMS on psychological craving,withdrawal symptom,mood and sleep disorders of heroin-dependent individuals and the intervention mechanism based on large-scale brain networks,as to provide a theoretical basis for r TMS treatment of heroin dependence.MethodsExperiment 1: Forty-six heroin addicts were randomized to receive real or sham highfrequency r TMS targeting the left DLPFC,and the changes of psychological craving,mood and sleep were observed by questionnaire before and after the intervention.Experiment 2: Seventeen subjects in the active r TMS group and 18 subjects in the sham r TMS group were screened from the subjects in experiment 1 who met the conditions of f MRI,and their psychological craving and f MRI data were collected before and after r TMS intervention.Meanwhile,f MRI data of 22 healthy subjects who did not receive r TMS intervention were included as a control group.To analyze the effects of r TMS on psychological craving and large-scale brain networks of heroin-dependent individuals.ResultsExperiment 1: After r TMS intervention,only the active r TMS group showed a significant decrease in the withdrawal symptom score,cue-induced craving score,BDI-Ⅱ score,HAMA scores and PSQI score(P < 0.05),but there was no significant decrease in sham r TMS group(P > 0.05).Experiment 2: After r TMS intervention,only the active r TMS group showed a significant decrease in spontaneous(t = 2.41;P < 0.05)and heroin cue-induced craving(t = 4.25;P< 0.001).The coupling between the left DLPFC(a key node of left ECN)and left parahippocampal gyrus(PHG,included in DMN)significantly increased in the active group with a tendency toward that of healthy controls.The coupling between the right precentral gyrus and three key regions included in DMN(posterior cingulate cortex/precuneus and bilateral inferior parietal cortex)significantly decreased in the active group with a tendency toward that of healthy controls.For the active r TMS individuals,the left DLPFC-PHG coupling negatively correlated with the spontaneous craving(r =-0.367,P < 0.05)and the drug cue-induced craving(r =-0.486,P < 0.01).Conclusion1.The r TMS targeting the left DLPFC significantly improved psychological cravings,withdrawal symptoms,mood and sleep disorders in heroin-dependent individuals.2.The mechanism of r TMS intervention on heroin dependence may be related to improving the function of the large-scale brain networks,and the mechanism of reducing the psychological craving may be related to the enhanced ECN-DMN coupling.