Brain Mechanism and Intervention of Executive-control Dysfunction Among Substance Dependents

Study Overview
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Brief Summary
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The investigators assume that tACS could improve amphetamine and alcohol dependent patients' executive-control function by adjusting the synchronization patterns and enhancing the functional connectivity of the prefrontal-ventral striatum pathway. A random controlled trial will be used to test the effect of θ-tACS treatment. Three months follow-up assessment will be conducted to test the changing of executive-control function and its mechanism.

Detailed Description
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Substance abuse has become a major social and public health problem in China, especially for amphetamine abuse and alcohol abuse. Executive-control dysfunction is the main symptom for substance dependents. Previous studies have demonstrated the relationship between cognitive dysfunction and prefrontal-ventral striatum pathway. Studies have shown that abnormal phase synchronization and phase-amplitude coupling (PAC) induced the impairment of cognitive, and tACS could improve executive-control function by adjusting the abnormal synchronization. But it has not been verified among MA or alcohol patients. The investigators assume that tACS could improve MA and alcohol dependent patients' executive-control function by adjusting the synchronization patterns and enhancing the functional connectivity of the prefrontal-ventral striatum pathway. A random controlled trial will be used to test the effect of θ-tACS treatment. Three months follow-up assessment will be conducted to test the changing of executive-control function and its mechanism. This study will provide a practical and theoretical basis for developing a novel treatment for substance dependents.

Official Title
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Brain Mechanism and Intervention of Executive-control Dysfunction Caused by Impaired Prefrontal-ventral Striatum Synchronization Among Substance Dependents

Conditions
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Substance Dependence, Executive Function Disorder, Transcranial Alternating Current Stimulation

Intervention / Treatment
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* Device: Transcranial alternating current stimulation-true stimulus
* Device: Transcranial alternating current stimulation-sham stimulus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-60, male or female, with 9 or more years of education, and able to complete questionnaire evaluation and behavioral tests Meet DSM-5 diagnostic criteria for amphetamine-type substance addiction or alcohol addiction Have used amphetamine or alcohol for at least one year (at least once a week) Normal vision and hearing, or within the normal range after correction Agree to cooperate in the follow-up evaluation No metal implantation in the head, no history of nerve problems or head injury, and no skin sensitivity Exclusion Criteria: Have severe cognitive impairment, such as a history of head trauma, cerebrovascular disease, epilepsy, etc. Have used drugs promoting cognitive function in the last 6 months Have impaired intelligence (IQ<70) Abuse or dependence of other psychoactive substances (except nicotine) in the last 5 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Healthy control group<br>No intervention is conducted in the healthy control group. | |
| Experimental: Intervention group of amphetamine addiction<br>A 20-minute tACS intervention of real-stimulus is conducted twice a day for a total of 10 days in the intervention group of amphetamine addiction. | Device: Transcranial alternating current stimulation-true stimulus<br>* The adhesive electrodes were placed at F3 and F4 positions of the 64-bit EEG caps of the 10-20 system, corresponding to bilateral prefrontal lobes respectively. Before the intervention, the individual alpha frequency (IAF) of the subjects was measured according to the average peak value of α waves at dorsolateral prefrontal cortex in the closed state. Then an alternating current at θ frequency (θ = IAF - 5Hz) was applied to each subject based on its IAF value. The amplitude of stimulation was increased with a step of 20μA starting from 0. When the subjects had a slight prickling sensation or optical illusion, the stimulation current was decreased with a step of 20μA until the sensation disappeared. The current value at this time was used as the stimulation current of the subjects.<br>|
| Sham Comparator: Control group of amphetamine addiction<br>A 20-minute tACS intervention of sham-stimulus is conducted twice a day for a total of 10 days in the control group of amphetamine addiction. | Device: Transcranial alternating current stimulation-sham stimulus<br>* The adhesive electrodes were placed at F3 and F4 positions of the 64-bit EEG caps of the 10-20 system, corresponding to bilateral prefrontal lobes respectively. The actual stimulation waveform was just implemented in the first 60 s (or more longer) and then faded out.<br>|
| Experimental: Intervention group of alcohol addiction<br>A 20-minute tACS intervention of real-stimulus is conducted twice a day for a total of 10 days in the intervention group of alcohol addiction. | Device: Transcranial alternating current stimulation-true stimulus<br>* The adhesive electrodes were placed at F3 and F4 positions of the 64-bit EEG caps of the 10-20 system, corresponding to bilateral prefrontal lobes respectively. Before the intervention, the individual alpha frequency (IAF) of the subjects was measured according to the average peak value of α waves at dorsolateral prefrontal cortex in the closed state. Then an alternating current at θ frequency (θ = IAF - 5Hz) was applied to each subject based on its IAF value. The amplitude of stimulation was increased with a step of 20μA starting from 0. When the subjects had a slight prickling sensation or optical illusion, the stimulation current was decreased with a step of 20μA until the sensation disappeared. The current value at this time was used as the stimulation current of the subjects.<br>|
| Sham Comparator: Control group of alcohol addiction<br>A 20-minute tACS intervention of sham-stimulus is conducted twice a day for a total of 10 days in the control group of alcohol addiction. | Device: Transcranial alternating current stimulation-sham stimulus<br>* The adhesive electrodes were placed at F3 and F4 positions of the 64-bit EEG caps of the 10-20 system, corresponding to bilateral prefrontal lobes respectively. The actual stimulation waveform was just implemented in the first 60 s (or more longer) and then faded out.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of inhibitory control ability | The change of inhibitory control ability will be reflected by participants' performance in the Go/No Go task. | baseline, immediately after the intervention, one month after the intervention, three months after the intervention | 
| The change of theta(θ) phase synchronicity | The change of θ phase synchronicity in the prefrontal - ventral striatum pathway in amphetamine addicts and alcohol addicts will be measured by EEG. | baseline, immediately after the intervention, one month after the intervention, three months after the intervention | 
| The change of theta-gamma phase amplitude coupling(θ-γ PAC) | The change of θ-γ PAC in the prefrontal - ventral striatum pathway in amphetamine addicts and alcohol addicts will be measured by EEG. | baseline, immediately after the intervention, one month after the intervention, three months after the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of working memory | The change of working memory will be measured by the two-back task. | baseline, immediately after the intervention, one month after the intervention, three months after the intervention | 
| DA metabolic rate | DA metabolism was measured by Positron Emission Computed Tomography | baseline | 
| The change of decision-making ability | The change of decision-making ability will be measured by the Balloon Analog Risk Task. | baseline, immediately after the intervention, one month after the intervention, three months after the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Substance dependence, Execution-control dysfunction, Synchronization, Transcranial alternating current stimulation