| BackgroundAs a noninvasive technique,computerized cognitive rehabilitation training(CCRT)could facilitate to improve the deteriorated cognitive function,increase response inhibition function,and enhance brain plasticity.Nowadays,CCRT has been widely applied to the treatment of substance use disorders,including alcohol,nicotine as well as stimulants.After systematic intervention,CCRT can significantly contributing to ameliorating the symptoms of cognitive deficits and increased impulsive control problems.ObjectiveIn this research,a newly developed Chinese version of computerized cognitive addiction therapy(CCAT)programwas used to test its effectiveness in treating cognitive dysfunction and impulse control disorder in moderate to severe methamphetamine use disorder patients,and providing a theoretic support for developing newly technique of substance use disorder during clinical treatment.Methods1.Through qualitative and literature research,methamphetamine cue related pictures were screened out,and applying these pictures in designing of methamphetamine cues related to computerized addiction cognitive therapy programs.2.Through randomized controlled trial design and blind method,40 subjects diagnosed with moderate to severe methamphetamine use disorder in compulsory isolation detoxification centers in Shanghai were randomly equally assigned into two groups.Patients in control group only participated in regular education in these rehabilitation centers,treatment do not involve specific interventions to improve cognitive functions.While for patients assigned to CCAT group,in addition to the regular education and intervention,they also received 4 weeks of CCAT therapies,including working memory training,attention control training and attention bias modification therapies.3.Behavioral assessment.All subjects’ cognitive function and impose control abilities were assessed both at baseline and after treatment.The Chinese version of Cog State Battery was used to assess the subjects’ cognitive function,including verbal learning and memory(international shopping lists task),problem-solving and error monitoring(Groton maze task),working memory(Two-Back task),visual learning and memory(continuous paired learning task)and social cognition(social emotional cognition task).Changing of impulse control function were assessed through delay discounting task(DDT),Iowa gambling task(IGT),and balloon analogue risk task(BART).4.Electrophysiology assessment.MA-Stroop task combined with event related potentials technique were used to exploring the patterns of methamphetamine related attention bias and prognosis trends of event related potentials elicited by stimulants and neutral words during MA-Stroop Task.Results1.Sixteen methamphetamine cues related pictures,including methamphetamine cracks,methamphetamine smoking equipment,and high relapse situations,were screened out as stimulus materials and integrated into the newly developed computerized cognitive addiction therapy program2.Through qualitative research combined with literature research,the finally developed Chinese version of computerized cognitive addiction therapy program involves training modules including working memory training,attention control training and attentional bias modification training.3.40 participants diagnosed with moderate to severe methamphetamine use disorder were recruited in compulsory isolation detoxification centers in shanghai.And there were not statistical significant difference between intervention group and control group(p<0.05).All subjects of each group successfully finished the 4-week CCAT and control treatment and research.4.After intervention,cogstate test revealed that,for verbal learning and memory function,international shopping list test showed significant group*time effect(F = 31.78,p = 0.000),with CCAT had a higher scores than control group.For spatial working memory function,continuous paired learning task showed significant time effect(F = 5.45,p = 0.020)and group effect(F = 5.95,p = 0.015),within group comparsion revealed CCAT group had a better performance than control group.Howerer,social cognitive test showed time*group effect(F = 6.68,p = 0.010)and time effect(F = 3.07,p = 0.080),within group test showed that,control group had a worse score compared to baseline,while CCAT group did not show such change.There were no statistically significant difference in attention and vigilance and working memory.5.After CCAT intervention,CCAT group also had a better average reductive ratio than control group on impulsive risk decision-making tests.In delay discoing task,all six delay time show significant time*group effect,and CCAT had better scores than control group.During Iowa gambling task show time*group effect(F = 49.07,p = 0.000),with CCAT group showed better promformance than control group.In balloon analogue risk task,all there measures,BART scores(F = 20.44,p = 0.000),average blowing number of unexploded balloons(F = 5.65,p = 0.017)and exploded balloons(F = 24.59,p = 0.000)showed time*group effect,with CCAT group show better improvements.6.Behavioral outcomes of MA-Stroop task GEE analyzing showed no significant difference between the two groups in terms of response time as well as response accuracy.However,results of GEE analyzing showed that there was a significant time effect before and after CCAT intervention(p = 0.01),and significant improvement was detected in patients with CCAT group before and after intervention(p = 0.01).7.The amplitude of event related potentials(ERPs)data showed that the difference between CCAT and control group lines methamphetamine related tasks.Significant vocabulary * group * time interaction effects were observed both in P2 amplitude(F = 12.04,p = 0.02)and N2 amplitude(F = 13.75,p = 0.01).Methamphetamine related P2(p = 0.00)and N2(p = 0.02)amplituate increased in during follow-up period.8.ERPs data analyzing using generalized estimation equation(GEE)technology on different ROIs revealed that,endogenous ERPs components N1 amplitude only showed significant group effect(F = 3.43,p = 0.06)over left-anterior areas.P2 amplitude showed significant vocabulary*group*time interaction(F = 372.96,p = 0.00)over medial-anterior areas.Post hoc test showed MA related P2 amplitude decreased in CCAT group(p = 0.00).For exogenous ERPs components,significant vocabulary*group*time interaction effect were discovered over left-anterior areas(F = 676.38,p = 0.00),medial-anterior areas(F = 11.00,p = 0.02)and right-anterior areas(F = 1022.25,p = 0.00).Post hoc test revealed that P3 amplitude increased in control group over left-anterior areas(p = 0.00).On the contrary,P3 amplitude decreased over medial-anterior areas(p = 0.01)and right-anterior areas(p = 0.00)in CCAT group.N2 amplitude showed significant vocabulary*group*time interaction effect(F = 21.77,p = 0.00)over right-anterior areas,with MA related amplitude increased in control group(p = 0.00),while no such changes were found in CCAT group.Conclusions1.Chinese version of computerized cognitive addiction therapy program can partly improving the cognitive function of patients with methamphetamine use disorders,especially working memory abilities.2.Impulse decision-making function can be improved through systematic CCAT therapy.3.Attention bias towards methamphetamine related cues were changed in CCAT group patients.4.Changes in the amplitude of event-related potential components in a particular area may reflect changes in brain plasticity in patients undergoing CCAT training. |
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