Cognitive And Gray Matter Deficits In Methamphetamine Dependence And RTMS Intervention Exploratory Study

Background Methamphetamine(MA)is a worldwide popular synthetic drug,long-term chronic use of MA can lead to various cognitive impairments,previous studies have implicated a multifactorial process underlying the methamphetamine dependence,yet the contribution of specific neural substrates and whether these abnormalities will remit over time has not been examined.rTMS is a novel non-invasive brain intervention with potential therapeutic effects on substance dependence,while the underlying mechanism remains to be further studied.Objective 1.To understand the cognitive and gray matter differences of MA dependent patients with different abstinences and potential related factors;2.To understand MA dependent patients’ cognitive function and gray matter alternations over time;3.Explore the possible benefits of rTMS intervention in cognitive function and gray matter for MA dependent patients.Methods 1.Case-control study: 79 MA-dependent patients were recruited and divided into 2 groups by the length of abstinence,29 MA-dependent patients with longer abstinence(>3 months)were included into rehabilitation group,the other 50 with shorter abstinent time(<3 months)were included into detoxification group.Demographic data and substance use history were collected,the Two-back task,the international shopping list task,and the Groton maze learning task,the social emotional cognitive task and the continuous pairing learning task were performed for cognitive function examination and T1 head magnetic resonance(MRI)was scanned.2.Cohort study: 29 MA-dependent patients in the rehabilitation group were enrolled in the cohort study.Cognitive function and MRI data were collected 6 months after baseline.3.Randomized double-blind clinical controlled study: 50 MA-dependent patients in the detoxification group were included in the rTMS intervention study.The enrolled patients were randomly divided into the real stimulation intervention group and the pseudo-stimulation control group,25 cases in each group.Cognitive function and MRI data were collected before and after intervention.The main outcome measurements were cognitive function recoveries,and the secondary outcome measurement was brain gray structure alternation.Results 1.(1)MA dependent rehabilitation group has better performance in the two-back task,international shopping list task,Groton maze learning task,social emotional cognitive task and continuous pairing learning task.Female MA-dependent patients perform better than men in international shopping list tasks.(2)The withdrawal time is positively correlated with cognitive performance,the initial age is negatively correlated with the Groton maze learning task error rate.(3)The gray matter volume and cortical thickness had a potential impact on cognitive function.(4)MA rehabilitation group had higher gray matter volume(GMV)in the right frontal lobe,higher cortical thickness in the superior temporal gyrus,lover GMV in the left occipital lobe and the right thalamus than the detoxification group.2.(1)The correct rate of Two-back task was increased at follow-up,female had better recovered than men.(2)The GMV was increased in the cerebellum and decreased in the right cingulate compared to the baseline.The cortical thickness in the left frontal lobe,the superior parietal gyrus,and the inferior parietal cortex were lower than baseline.3.(1)No significance was found in cognitive function at baseline between true and sham stimulation group,and the true stimulation group had higher recovery rate in the international shopping list task after intervention.(2)With refer to social emotional cognitive task,in true stimulation group the male recovered better,while in the pseudo-stimulation group the female recovered better.(3)The true stimulation group had higher GMV in the left cerebellum and frontal lobe compared with the pseudo-stimulation group,and higher potential cortical thickness in bilateral calcarine,lingual and the right middle frontal cortex.Conclusions 1.longer abstinent MA dependent patients had better cognitive function and gray matter condition than those with shorter abstinence.Cognitive function is related with withdrawal time,initial age,gender and brain gray matter.2.The gray matter of MA dependent patients had dynamic alternation over time,presented in both increasing and decreasing potential.3.rTMS intervention contributes to the recovery of cognitive function and gray matter for MA dependent patients.