Effects of Subconscious Memory Extinction in Patients With Alcohol Dependence and Its Mechanism

In this study, the subconscious memory extinction therapy based on very brief exposure is used to intervene to reduce the alcohol craving of alcohol-dependent patients, prevent relapse, and observe the psychological craving, heart rate, skin conductance, and pupil diameter changes of the patients during the brief exposure extinction. The main questions it aims to answer are: Whether subconscious extinction intervention would reduce psychological craving and alcohol relapse? What is the mechanism of subconscious extinction intervention in alcohol dependence?

After being informed about the study and potential risks, all patients giving written informed consent will undergo a screening period to determine eligibility for study entry. patients who meet the eligibility requirements will be randomized in very brief extinction, clearly visible extinction, or very brief neutral extinction. This study will recruit alcohol-dependent participants aged 18-60 in the ward, observe reported subjective scores during the extinction, and record the heart rate, skin conductance, pupil diameter, and ERP changes.

Enrolled participants would receive very brief extinction approximately 25 minutes per day for 2 days.

Enrolled participants would receive very brief neutral extinction for approximately 25 minutes per day for 2 days.

Enrolled participants would receive clearly visible extinction therapy for approximately 25 minutes per day for 2 days.

The very brief extinction presents a very short (33ms) repetitive sequence of alcohol cues, followed by a "masking" stimulus(117ms), which masks the alcohol cues. In the case of repeated exposure to alcohol stimulation, the response to the stimulation is desensitized at the level of unconscious processing.

The clearly visible extinction presents a repetitive sequence of alcohol cues(150ms) without a "masking" stimulus. In the case of repeat exposure to alcohol stimulation, the response to the stimulation is desensitized at the level of conscious processing.

The very brief neutral extinction presents a very short (33ms) repetitive sequence of neutral cues, followed by a "masking" stimulus(117ms), which masks the neutral cues. In the case of repeated exposure to neutral stimulation, the response to the stimulation is desensitized at the level of unconscious processing.

Alcohol-specific Visual Analog Scale is a valid measurements of craving for a alcohol. Possible scores range from 0(no craving) to 10 (want to drink imediately). Change= (week 1 score - baseline score)

Percentage of participants who relapse by assuming that drinking alcohol on more than 3 days in a month in anunrestricted environment is re-drinking

Thus skin conductance level can serve as a stable and useful index of autonomic arousal in clinical trials. Skin conductance signals are measured via electrodes placed on fingertips, arrange from 0 to 50 uS.

The pupil diameter is measured by Eyelink 1000 plus eyetracking, Pupil size data are available with every data point collected by the EyeLink 1000 Plus. To evaluate the level of accuracy obtained in pupil size measures, dots between 2.0 and 5.0 mm in diameter were laser printed.

An ERP is a technique that can be used to assess how the brain is functioning in response to stimulation. Event-related potentials (ERPs) are derived from electroencephalographic (EEG) measurement of neural activity. The 64-channel EEG system from Brain Products company would be used to measure P300, N400, and slow potential.

Inclusion Criteria: Adopt DSM-IV alcohol dependence diagnostic criteria; Complete detoxification treatment without obvious withdrawal symptoms; Informed consent, voluntary participation. Exclusion criteria: Acute alcohol dependence withdrawal period; Patients who meet the DSM-Ⅳ diagnosis of psychoactive substances or non-psychoactive substances other than alcohol (except nicotine); Previous acceptance experienced similar exposure therapy;