Exploring the Mechanisms and Efficacy of Cerebellum-Medial Prefrontal Cortex-Based Paired-Pulse Repetitive Transcranial Magnetic Stimulation for Methamphetamine Use Disorder
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- cognitive flexibility
研究概览
简要总结
To investigate the mechanism and efficacy of a novel repetitive transcranial magnetic stimulation (rTMS) intervention model with paired cerebellar-medial prefrontal cortex (mPFC) pulses on methamphetamine use disorder patients and to develop a novel physiotherapeutic intervention to optimise the treatment and management.
详细描述
Numerous studies have shown that impaired cerebellar- mPFC functional connectivity leads to impaired social preferences and behavioural flexibility and more persistent drug use in addicts. Cerebellar and mPFC paired-pulse rTMS interventions may enhance functional connectivity, effectively modulate cerebellar-prefrontal loops, reduce craving, improve cognitive flexibility, and modulate cortical excitability. The aim of this project is to investigate the mechanism and efficacy of a novel paired-pulse rTMS intervention targeting the cerebellar-mPFC circuit in patients with methamphetamine use disorder, in order to develop innovative physiotherapeutic interventions and to optimize treatment and clinical management for individuals with addiction.
Prior to initiating the intervention, it was essential to determine the optimal inter-stimulus interval (ISI) for the cerebellar-mPFC paired associative stimulation. Therefore, a mechanistic study was conducted from December 2024 to June 2025 at the Chengdu Drug Rehabilitation Center in Sichuan Province before the interventional trial commenced. A mixed design was employed, contrasting single-pulse mPFC stimulation with cerebellum→mPFC cortico-cortical paired associative stimulation (ccPAS) at inter-stimulus intervals of 6 ms and 45 ms. The results revealed that individuals with methamphetamine use disorder exhibited aberrant mPFC cortical excitability compared to healthy controls. Importantly, cerebellar-mPFC ccPAS with a 6-ms ISI was found to specifically modulate mPFC cortical excitability.
Therefore, based on the identified 6-ms cerebellar-mPFC stimulation interval, the current interventional study continues to implement a long-term, dual-coil combined stimulation protocol to further evaluate and establish its therapeutic efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Participants will be eligible for inclusion if they meet the following criteria:
- •Methamphetamine is the primary substance of use, and the participant meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for moderate or severe methamphetamine use disorder;
- •aged 18 to 60 years;
- •normal or corrected-to-normal vision and hearing, and right-handedness;
- •primary school education or above, with the ability to understand the questionnaires and behavioral task instructions.
排除标准
- •Participants will be excluded if they meet any of the following criteria:
- •presence of metal objects in the body, such as metal dentures, orthodontic braces, bone fixation plates, aneurysm clips, or other metallic implants;
- •severe physical illness or chronic disease, including heart disease, severe hypertension, stroke, epilepsy, or history of head trauma;
- •comorbid psychiatric disorders, such as bipolar disorder, schizophrenia, or severe depression;
- •previous participation in transcranial magnetic stimulation- or electroencephalography-related studies;
- •refusal to participate in the study, poor compliance, or any other contraindications to transcranial magnetic stimulation.
研究组 & 干预措施
Cerebellar-mPFC Dual-Coil Paired-Pulse TMS Intervention Group
The stimulation protocol involved delivering a pulse to the cerebellum first, followed by a pulse to the mPFC after a 6ms inter-stimulus interval (ISI). This 6ms interval was determined based on findings from our prior mechanistic study.
干预措施: Paired Associative Stimulation Targeting the Cerebellar-mPFC (Device)
结局指标
主要结局
cognitive flexibility
时间窗: Probabilistic reversal learning task: baseline, post-intervention, and at a follow-up session one weeks later; Volatile reversal learning task and Wisconsin Card Sorting Test: baseline and post-intervention; The CFI scale: baseline.
Based on tasks and scales assessing cognitive flexibility, including: 1.Probabilistic reversal learning task (The matching of symbols and pictures was reversed without informing the subjects and their cognitive flexibility in the reversed condition was assessed); 2.Volatile reversal learning task (participants were presented with two stimuli associated with their potential feedback magnitude. They were instructed to choose one of the two stimuli to receive feedback, but only one stimulus would result in feedback. ); 3.The Wisconsin Card Sorting Test (WCST) (a classic neuropsychological task where participants match response cards to four key cards based on hidden sorting rules (color, shape, or number). They receive "right" or "wrong" feedback after each match and must deduce the current rule, which changes without warning after several consecutive correct matches.); 4. The Cognitive Flexibility Inventory (CFI) scale is a 20-item self-report measure.
次要结局
- Craving(before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.)
- Electroencephalographic (EEG) Electrophysiological Results(before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.)
- response inhibition(SST task: baseline, post-intervention, and at a follow-up session one weeks later; BIS-11 scale: baseline.)
- Depression(before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.)
- Anxiety(before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.)
- stress levels(before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.)
- sleep quality(before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.)