BackgroundCognitive rehabilitation therapy has been found to improve cognitive deficits and impulse control problems in methamphetamine use disorder (MUD). However, there is limited research regarding this therapy’s feasibility when using mobile-based health technologies in supporting recovery from MUD in China.ObjectiveThe main aim of this study was to test whether 4 weeks of a newly designed computerized cognitive addiction therapy (CCAT) app can improve cognitive impairments, eliminate drug-related attention bias, and attenuate risk decision-making behaviors in participants with MUD.MethodsForty MUD participants were assigned randomly to either the CCAT group (n=20), who received 4 weeks of CCAT plus regular detoxification treatment as usual, or the control group (n=20), who only received the regular detoxification treatment as usual, in drug rehabilitation centers in Shanghai. The CCAT was designed by combine methamphetamine use-related picture stimuli with cognitive training with the aim of improving cognitive function and eliminating drug-related attention bias. The CogState Battery, Delay Discounting Task (DDT), Iowa Gambling Task (IGT), and Balloon Analog Risk Task (BART) were administered face-to-face to all participants before and after CCAT interventions.ResultsForty male patients were recruited. The mean age was 32.70 (SD 5.27) years in the CCAT group and mean 35.05 (SD 8.02) years in the control group. Compared to the control group, CCAT improved working memory in the CCAT group (P=.01). Group×time interactions were observed among DDT, IGT, and BART tasks, with rates of discounting delayed rewards, IGT, and BART scores (P<.001) being reduced among those who received CCAT, whereas no changes were found in the control group.ConclusionsThe newly designed CCAT can help to improve cognitive impairment and impulsive control in MUD. Further study is needed to understand the underlying brain mechanisms of the cognitive therapy.Trial RegistrationClinicalTrials.gov NCT03318081; https://clinicaltrials.gov/ct2/show/NCT03318081 (Archived by WebCite at https://clinicaltrials.gov/ct2/show/NCT03318081)

Background The prefrontal-striatal circuit is a core circuit related to substance dependence. Previous studies have found that repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) (key region of executive network) had limited responses, while inhibiting hyperactivation of ventromedial prefrontal cortex (vmPFC) (key region of limbic network) may be another strategy. However, there is currently no comparison between these two treatment locations. Methods Seventy-four methamphetamine-dependent patients were randomly assigned to one of treatment groups with two-week treatment: (1) Group A: intermittent theta-burst stimulation (iTBS) targeting the left DLPFC; (2) Group B: continuous theta-burst stimulation (cTBS) targeting the left vmPFC; (3) Group C: a combination of treatment protocol of Group A and Group B; (4) Group D: sham theta-burst stimulation. The primary endpoint was the change of cue-induced craving. The trial was registered at ClinicalTrials.gov (NCT03736317). Findings The three real TBS groups had more craving decrease effect than the sham group ( p <0.01). The changes of craving were positively correlated with the improvement of anxiety and withdrawal symptom. With the highest respondence rate, group C also had shorter respondence time than Group A ( p = 0.03). Group C was effective in improve depression symptoms ( p = 0.04) and withdrawal symptom ( p = 0.02) compared with Group D. Besides, Group C was significant in improve sleep quality ( p = 0.04) compared with Group A. Baseline depression scores and spatial working memory were positively predicting the intervention response. Interpretation The rTMS paradigms involving vmPFC with cTBS are optimized protocols and well-tolerated for methamphetamine-dependent individuals, and they may have better efficacies compared with DLPFC iTBS. Emotion and cognitive function are rTMS treatment response predictors for methamphetamine-dependent patients. Funding This work was supported by the National Key R&D Program of China (2017YFC1310400), National Natural Science Foundation of China (81,771,436, 81,801,319, 81,601,164), Shanghai Municipal Health and Family Planning Commission (2017ZZ02021), Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai (2017YQ013), Qihang Project of Shanghai Mental Health Center (2019-QH-05), Shanghai Sailing Program (19YF1442100), Shanghai Key Laboratory of Psychotic Disorders (13DZ2260500), Program of Shanghai Academic Research Leader (17XD1403300), Shanghai Municipal Science and Technology Major Project (2018SHZDZX05), and Shanghai Clinical Research Center for Mental Health (19MC1911100).

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Methamphetamine (MA) chronic users show risky decision-making deficits. However, the neural mechanisms underlying these deficits remain unclear. A case-control study was conducted to understand how MA users and healthy controls differ in electrophysiological responses associated with series decision-making. Electroencephalography of 31 MA users and 27 healthy controls was recorded when they performed the Balloon Analogue Risk Task involving risky decision-making with uncertain gain or loss. Feedback-related negativity (FRN) was measured and their association with their risky decision-making and impulsivity were examined. Compared to healthy controls, MA users showed smaller peak FRN amplitudes in fronto-central electrodes (F (1, 56) =4.559, p=0.037), and the attenuated peak FRN amplitudes correlated with more risk-taking behavior (r=0.48, p=0.012). Besides, MA users exhibited later FRN (F (1, 56) = 7.561, p=0.008) and earlier P300 (F (1, 56) = 3.582, p = 0.041) compared to healthy controls in fronto-central electrodes, which were correlated with higher score of impulsivity. These findings provided further evidence that MA users showed insensitivity to negative feedback in risky decisionmaking. FRN might be a promising biomarker of dependence.