The Effect And Mechanism Of Repetitive Transcranial Magnetic Stimulation On Amphetamine Type Stimulant Use Disorder

Background As a noninvasive electrophysiological technique,repetitive TMS(rTMS)could increase or decrease cortical excitability of target brain region,enhance neuron plasticity and brain connections,and increase cerebral cortex inhibition function.Nowadays,rTMS has been widely used in the treatment of substance use disorders,it can significantly reduce craving,improve emotional problems and cognitive function,improve withdrawal rate for alcohol,nicotine,cocaine.The mechanism may be related that rTMS could modulate inhibition ability of cerebral cortex and the release of glutamate and GABA.Glutamate and gamma-aminobutyric acid(GABA),the two main excitatory and inhibitory neurotransmitters in central nervous system,together maintain the balance of excitability of the nervous system.In recent years glutamate/GABA system has been attracted much attention in the pathogenesis of drug addiction.Studies have shown that prefrontal-striatal glutamate/GABA system is closely related to losing control in substance abuse and addiction.Objective The study aims to explore the effect and mechanism of rTMS on craving and cognitive dysfunction of amphetamine stimulants use disorders,as to provide theoretical basis of rTMS for amphetamine stimulants use treatment.Furthermore,to explore the role of GABA/glutamate system in craving and cognitive impairment in amphetamine use disorders.Methods 1.Thirty methamphetamine-addicted patients were randomized to receive 5 sessions of 8 min sham or 10 Hz rTMS to the left DLPFC.Subjects rated their craving and cognition at baseline,after exposed to methamphetamine-associated cues and after rTMS sessions by VAS and Cogstete.2.Forty methamphetamine-addicted patients were randomized to receive 20 sessions of 5 min sham or iTBS rTMS to the left DLPFC.Subjects rated their craving,motor threshold(MT)and cognition at baseline,after exposed to methamphetamine-associated cues and every week after rTMS sessions.3.GABA,glutamate and glutamine and other metabolites of the left dorsolateral prefrontal cortex were determined by magnetic resonance spectroscopy(MRS)before and after iTBS intervention.30 methamphetamine-addicted patients were selectd from long-term intervention group(n = 15 each group),and compared with 16 healthy controls.MethodsResults 1.Real rTMS over the left DLPFC reduced craving significantly after 5 sessions of rTMS as compared to sham stimulation(p<0.05).Furthermore,real rTMS improved verbal learning and memory(p=0.03)and social cognition(p=0.023)in MA-addicted patients.2.Real rTMS over the left DLPFC reduced craving significantly after 20 sessions of iTBS rTMS as compared to sham stimulation(p<0.05).Furthermore,real rTMS improved verbal learning and memory(p=0.006)and problem solving(p=0.003)in MA-addicted patients.Although real rTMS had no effect on social cognition,the social emotional cognition task accuracy scores decreased in the sham group(p-0.011).Motor threshold descended after first week of real iTBS in methamphetamine users(p<0.05)and returned to baseline level after 4 weeks.3.Magnetic resonance spectroscopy(MRS)showed that GSH,GPC,Ins,GPC + PCh PCr,Glu+ Gln of MA users were higher than the control group,only NAAG and NAA +NAAG were lower than control group.iTBS over the left DLPFC decreased GABA levels(p = 0.040),but had effect on other metabolites levels.While in sham stimulation group,Glu,Ins,Cr + PCr,Glu + Gln are decreased(p < 0.05)after the intervention.Conclusions 1.rTMS of the left DLPFC may reduce craving and have no negative effects on cognitive function in MA-addicted patients,supporting the safety of rTMS in treating MA addiction.2.Glutamate/GABA levels of the left dorsolateral prefrontal cortex were involved in the effect and mechanism of rTMS on methamphetamine addiction.The mechanism of treatment maybe related that rTMS could reduce GABA levels and keep the level of glutamate and glutamine.