Modification of Cue Reactivity by Neurofeedback in Human Addiction

Study Overview
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Brief Summary
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The project is geared towards the understanding of how to increase cognitive control over cue reactivity and drug craving.

Detailed Description
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Project C04 aims at assessing the combined effect of two interventions targeting at reducing striatal cue reactivity and increasing cognitive control, namely mindfulness-based intervention and real-time fMRI neurofeedback. Firstly, the investigators will test whether a prior mindfulness-based intervention (WP1) is able to enhance the effect of rtfMRI NFB (WP2) and change the networks involved in regulation of cue reactivity by providing participants with explicit strategies. Secondly, the investigators will investigate whether this combined intervention leads to a better clinical outcome in terms of decreased heavy drinking days and a reduced sum of alcohol consumption three months later.

Official Title
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Modification of Cue Reactivity by Neurofeedback in Human Addiction

Conditions
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Alcohol Use Disorder (AUD)

Intervention / Treatment
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* Behavioral: Treatment as usual (TAU) and neurofeedback (NFB)
* Behavioral: mindfulness-based relapse prevention (MBRP) and NFB
* Behavioral: TAU and sham NFB
* Behavioral: MBT and sham NFB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: alcohol use disorder according to DSM-5 ability to provide fully informed consent and to use self-rating scales abstinent after detoxification for at least 5 days sufficient understanding of the German language Exclusion Criteria: lifetime history of DSM-5 bipolar, psychotic disorder, or substance dependence other than alcohol or nicotine dependence current substance use other than nicotine and/or mild to moderate recreational use of cannabis as evidenced by positive urine test current threshold DSM-5 diagnosis of any of the following disorders: current (hypo)manic episode, major depressive disorder, generalized anxiety disorder, PTSD, borderline personality disorder, or obsessive compulsive disorder history of severe head trauma or other severe central neurological disorders (dementia, Parkinson's disease, multiple sclerosis) pregnancy or nursing infants use of medications or drugs known to interact with the CNS within the last 10 days, with testing at least four half-lives post last intake

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Experimental: NFB + (MBRP)<br>Neurofeedback (NFB) from target region or control region plus Mindfulness-based relapse prevention (for some) | Behavioral: Treatment as usual (TAU) and neurofeedback (NFB)<br>* This group will receive Treatment as usual (TAU) and neurofeedback (NFB). During NFB, participants will be asked to regulate the signal from a target brain region during the presentation of alcohol cues. The ventral striatum was chosen as target region.<br>Behavioral: mindfulness-based relapse prevention (MBRP) and NFB<br>* This group will receive MBRP and neurofeedback (NFB). MBRP consists of 5 extensive sessions of a specific manualized mindfulness-based intervention for alcohol dependent patients which will be carried out by trained psychologists and psychotherapists. During NFB, participants will be asked to regulate the signal from a target brain region during the presentation of alcohol cues. The ventral striatum was chosen as a target region.<br>Behavioral: MBT and sham NFB<br>* This group will receive MBRP and sham NFB. MBRP consists of 5 extensive sessions of a specific manualized mindfulness-based intervention for alcohol dependent patients which will be carried out by trained psychologists and psychotherapists. Sham NFB means that the signal displayed to the participant is based on activity in a control region, the auditory cortex, which is not involved in cue reactivity.<br>|
| Active Comparator: TAU and sham NFB<br>TAU + Neurofeedback (NFB) from control region | Behavioral: TAU and sham NFB<br>* This group will receive TAU and sham NFB. Sham NFB means that the signal displayed to the participant is based on activity in a control region, the auditory cortex, which is not involved in cue reactivity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neural Level: Blood Oxygen Level Dependent Signal within the ventral striatum | Change of the ability to volitionally modulate brain activation to alcohol cues after training in the target area. | 3 consecutive days within up to two weeks | 
| Clinical Level: Number of relapses | MBT and NFB will each lead to a reduced number of relapses during three months after treatment in comparison to the combination of TAU and sham NFB. The combined intervention is expected to lead to a larger reduction compared to the other groups. The investigators expect a higher number of days until relapse, a lower number of heavy drinking days and a lower amount of alcohol consumed by the participants during the follow-up period showing similar group differences. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional changes in brain networks | Functional changes in brain networks related to cognitive control during cognitive task performance between baseline and post-neurofeedback fMRI sessions. | up to two weeks | 
| Drinking type | Short question on which kind of drinking type the participant identifies with the most | up to two weeks | 
| Form 90 (Miller, 1996) | Primary dependent measure of alcohol consumption | up to two weeks | 
| Baratt Impulsiveness Scale (BIS-15) (Meule et al., 2011) | Questionnaire assessing personality/behavioral construct of impulsivity. Scores range from 15 to 60. The BIS-15 has a four-point rating scale with a minimum value of 1 (1 = seldom/never) to a maximum of 4 (4 = almost always/always). Lower scores indicate less impulsivity and higher score mean more impulsivity. | up to two weeks | 
| Sensory Inventory (SI): self-assessment of sensory sensitivity for adults and adolescents (Zamoscik et al., 2017) | Questionnaire on self-assessment of sensory sensitivity. Minimum value: 1 representing never. maximum value: 7 representing almost always. Higher scores indicate higher sensitivity for sensory influences. | up to two weeks | 
| General depression scale (german: Allgemeine Depressionsskala) (Radloff, 1977) | Self-assessment of depressive symptoms. minimum: 0 representing seldom, maximum: 3 representing mostly. Higher scores indicate stronger depression. | up to two weeks | 
| Positive and Negative Affect Schedule (PANAS) (Watson et al., 1988) | measures mood/emotion. minimum: 1 representing not at all, maximum: 5 representing very much. Depending on the item, higher scores represent higher levels of positive affect and lower scores represent lower levels of negative affect. | up to two weeks. | 
| Perceived Stress Scale (PSS) (Cohen et al., 1983) | measures stress. minimum: 1 representing never. maximum: 5 representing quite often. Higher scores indicate higher levels of perceived stress. | up to two weeks | 
| Behavioral Inhibition/Approach System (BIS/BAS) (Carver & White, 1994) | assessing individual differences in the sensitivity of the behavioral approach and the behavioral avoidance system. | up to two weeks | 
| Fagerström Test of Nicotine Dependence (Heatherton et al., 1991) | assessing nicotine dependence | up to two weeks | 
| Visual Craving Scale | Visual Analogue Scale for craving | up to two weeks | 
| Vocabulary test | Neuropsychological test | Collected once during the baseline assessment | 
| Dot-probe task with alcohol stimuli | Change in attentional bias to alcohol-related cues. | Collected once during the baseline assessment | 
| Dimensional card sorting task (Zelazo, 2006) | Neuropsychological test | Collected once during the baseline assessment | 
| Cue reactivity task (Vollstädt-Klein et al., 2011) | fMRI task. Change in BOLD during cue reactivity task. | 2 timepoints: Before and after 2 weeks of neurofeedback. | 
| Alcohol Abstinence Self-Efficacy Scale (DiClemente et al., 1994) | measure of craving. minimum: 1 representing not at all, maximum: 5 representing enormous. Higher scores indicate a high perceived temptation to drink. | 2 weeks | 
| Alcohol Urge Questionnaire (Bohn et al., 1995) | measure of craving | 2 weeks | 
| Alcohol Dependence Scale (Ackermann et al., 1999) | measure of craving. Range/response options vary depending on the question. Higher scores are predictive of DSM diagnosis of alcohol dependence. | 2 weeks | 
| German Inventory of Drinking Situations (DITS-40) (Victorio-Estrada, 1993) | measure of craving. minimum: 0 representing never, maximum: 3 representing almost always. Higher scores indicate a higher frequency to drink. | 2 weeks | 
| Craving Automated Scale for Alcohol (CASA) (Vollstädt-Klein et al., 2015) | measure of craving. minimum: 0 representing never, maximum: 5 representing always. Higher scores indicate automated craving. | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcohol use disorder, mindfulness-based intervention, neurofeedback, ventral striatum