To investigate the mechanism and efficacy of a novel repetitive transcranial magnetic stimulation (rTMS) intervention model with paired medial prefrontal cortex (mPFC) -cerebellar pulses on methamphetamine use in patients and to develop a novel physiotherapeutic intervention to optimise the treatment and management of addicted patients.
Numerous studies have shown that impaired mPFC-cerebellar 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 reduce relapse risk. The aim of this project is to investigate the mechanism and efficacy of a novel paired-pulse rTMS intervention targeting the mPFC-cerebellar 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 cerebellar-mPFC circuit connectivity compared to healthy controls. Importantly, cerebellar-mPFC ccPAS with a 6-ms ISI was found to specifically modulate this inter-regional circuit dysfunction. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
70
The protocol consisted of 180 pulse trains. Each train contained 5 pulse pairs delivered over 1 second, resulting in a stimulation frequency of 5 Hz. Within each pulse pair, the cerebellum was stimulated first, followed by the mPFC after a 6-ms inter-stimulus interval (ISI). In total, 900 pulse pairs were administered, and a complete intervention session lasted 11 minutes and 57 seconds.
The coil will be placed vertically over the cerebellar and mPFC brain regions, allowing participants to perceive the coil's vibration and sound without receiving effective intervention. All other stimulation parameters are identical to those in the active intervention group.
Min Zhao, PhD
Shanghai, Shanghai Municipality, China
RECRUITINGcognitive flexibility
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.
Time frame: 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.
Craving
1、The intensity of psychological craving in MA dependents was assessed using the Visual Analogue Scale (VAS), where individuals rated their cravings on a scale from 0 to 100, with higher scores indicating greater levels of craving. 2、Desires for drug questionnaire (DDQ) consists of 13 items designed to assess an individual's current thoughts and preoccupations related to drug use. 3、Obsessive Compulsive Drug Use Scale (OCDUS)consists of 13 items designed to assess an individual's current thoughts and preoccupations related to drug use.
Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
Electroencephalographic (EEG) Electrophysiological Results
This includes analyses of TMS-EEG, resting-state EEG, and task-state EEG data across temporal, frequency, and time-frequency domains.
Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
response inhibition
The Stop-Signal Task (SST) is a seminal experimental paradigm in cognitive psychology and neuroscience designed to objectively measure an individual's response inhibition-the ability to actively suppress a prepotent or already-initiated motor response. To gain a more comprehensive understanding of an individual's inhibitory control, it is highly informative to complement this with a trait-based, self-reported measure of impulsivity. The Barratt Impulsiveness Scale, Version 11 (BIS-11) serves this purpose. The BIS-11 is a widely validated questionnaire that assesses stable, cross-situational personality traits related to impulsivity across three core dimensions: Attentional Impulsiveness (inability to focus attention), Motor Impulsiveness (tendency to act without thinking), and Non-Planning Impulsiveness (lack of forethought).
Time frame: SST task: baseline, post-intervention, and at a follow-up session one weeks later; BIS-11 scale: baseline.
Depression
The reduction rate of Beck Depression Inventory (BDI) scores was calculated from baseline to post-intervention and follow-up assessments to quantify the decrease in depressive symptom severity.
Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
Anxiety
The reduction rate in the Beck Anxiety Inventory (BAI) scores was calculated from baseline to post-intervention and follow-up assessments to quantify the decrease in anxiety symptom severity.
Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
stress levels
The reduction rate of Perceived Stress Scale (PSS) scores was calculated from baseline to post-intervention and follow-up assessments to quantify the decrease in perceived stress levels.
Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
sleep quality
The reduction rate of Pittsburgh Sleep Quality Index (PSQI) global scores was calculated from baseline to post-intervention and follow-up assessments to quantify the improvement in sleep quality.
Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.