Neurocognitive and Neurobehavioral Mechanisms of Change Following Psychological Treatment for Alcohol Use Disorder

Although pharmacological and psychosocial treatments for alcohol use disorders (AUDs) exist that improve outcomes over natural recovery (Finney et al., 2013), outcomes are still modest. Identifying mechanisms of behavior change (MOBCs) that lead to successful outcomes may be critical for efforts to improve existing treatments or to better match patients with particular treatments. The goal of the proposed research is to conduct a randomized clinical trial to systematically examine pretreatment neurocognitive and behavioral characteristics and changes in brain function over time during two empirically supported treatments for AUD. One hundred forty treatment-seeking individuals with an AUD will be randomized to receive either 8 weeks of Cognitive Behavioral Treatment (CBT) or Mindfulness Based Treatment (MBT) after receiving 4 weeks of a platform treatment that focuses on enhancing motivation to change. Neurocognitive and behavioral characteristics will be measured using neuroimaging, comprehensive behavioral assessments, and patient self-reports. To establish the temporal relationship between changes in drinking and changes in these MOBCs, patients will be assessed at: (a) baseline; (b) four weeks into treatment; (c) immediately post-treatment; and (d) 9- and 15-months post-baseline. Self-report measures and behavioral tasks will be administered at monthly intervals during treatment; and fMRI will be collected at baseline, and at 3, and 9-months post baseline. The primary aim of the study is to examine the effects of the treatments on three hypothesized mechanisms: craving/regulation of craving, cognitive and behavioral control, and regulation of affect/arousal. The secondary aim will identify neurocognitive and behavioral baseline characteristics predictive of reductions in drinking over time and differential patterns of response to CBT or MBT.

• Cognitive Behavior Therapy (Behavioral): The CBT condition will include 8 weekly, 60-minute sessions, and will be delivered according to the Epstein \& McCrady (2009) cognitive-behavioral treatment manual, excluding material provided in the platform treatment. The treatment manual and accompanying client workbook provide detailed therapist instructions for each session, client exercises, worksheets, and homework assignments. The treatment focuses on cognitive and behavioral coping skills training, and emphasizes problem-solving as an overall approach to dealing with drinking. Treatment sessions may be audio-recorded for supervision and to ensure that the treatment is being delivered as intended.
• Mindfulness Based Relapse Prevention (Behavioral): The MBT condition will be adapted from the 8-week version of the mindfulness-based relapse prevention (MBRP) manual (Bowen et al., 2011; Witkiewitz et al., 2005). The main adaptation will be to eliminate the relapse prevention/CBT components and focus attention on mindfulness practices. The mindfulness practices in MBT are designed to increase awareness of triggers and decrease reactivity to distress or discomfort in the presence of triggers (Witkiewitz \& Bowen, 2010). The relevant worksheets and homework assignments focusing on mindfulness tools will be maintained from the MBRP manual. Treatment sessions may be audio-recorded for supervision and to ensure that the treatment is being delivered as intended.

Primary outcomes

• Percent heavy drinking days [Baseline, 4-week within treatment visit, 8-week within treatment visit, and 3-month follow-up, 9-month follow-up, and 15-month follow-up]: The Form 90 will be used to derive estimates of the outcome: percent heavy drinking days, where heavy drinking is defined as 4+ drinks per occasion for women and 5+ drinks per occasion for men.

Secondary outcomes

• Percent drinking days [Baseline, 4-week within treatment visit, 8-week within treatment visit, and 3-month follow-up, 9-month follow-up, and 15-month follow-up]: The Form 90 will be used to derive estimates of the outcome percent drinking days.
• MOBC: Craving - self report [Up to 15 months]: The Penn Alcohol Craving Scale will be used to examine changes in craving that occur during and after treatment. Ratings range from 1-6, with higher scores indicating a higher level of craving.
• MOBC: Regulation of Affect/Arousal - negative affect self-report [Up to 15 months]: The Negative Affect Summary score from the National Institutes of Health Negative Emotions toolbox will be used to assess overall negative affect changes during and after treatment. T-scores on the measure can range from 1-100, with higher scores indicating a higher level of negative affect.
• MOBC: Regulation of Affect/Arousal - neuroimaging [Up to 9 months]: The difference in percent signal change during negative vs. neutral picture cues in amygdala will be assessed using a cue task while participants are scanned using functional magnetic resonance imaging.
• MOBC: Cognitive and Behavioral Control - neuroimaging errors [Up to 9 months]: The difference in percent signal change during unsuccessful inhibition of responses vs. successful non-inhibition trials in dorsal anterior cingulate cortex will be assessed using a stop signal task while participants are scanned using functional magnetic resonance imaging.
• MOBC: Cognitive and Behavioral Control - neuroimaging inhibition [Up to 9 months]: The difference in percent signal change during successful inhibition of responses vs. successful non-inhibition trials in right inferior frontal cortex will be assessed using a stop signal task while participants are scanned using functional magnetic resonance imaging.
• MOBC: Cognitive and Behavioral Control - behavior [Up to 15 months]: The Monetary Choice Questionnaire will be used to determine the degree to which impulsive choice changes during and after treatment. A discounting rate (k) will be computed for each administration.
• MOBC: Cognitive and Behavioral Control - self report impulsivity [Up to 15 months]: The UPPS-P Impulsive Behavior Scale will be used to examine changes in impulsivity that occur during and after treatment. Potential total scores range from 59-236, with higher scores indicating a higher level of impulsivity.
• MOBC: Craving - neuroimaging [Up to 9 months]: The difference in percent signal change during alcohol vs. neutral picture cues in ventral striatum will be assessed using a cue task while participants are scanned using functional magnetic resonance imaging
• Drinks per drinking day [Baseline, 4-week within treatment visit, 8-week within treatment visit, and 3-month follow-up, 9-month follow-up, and 15-month follow-up]: The Form 90 will be used to derive estimates of the outcome: drinks (standard drink=14 grams of pure alcohol) per drinking day.

Sex: All, ages: 22 Years to 85 Years

Inclusion Criteria:

1. Age 22-85 years
2. Self-identify as a heavy/binge/weekly drinker
3. Engage in "hazardous and harmful alcohol use" (Babor et al., 2001) based on an AUDIT score > 8 for men and > 7 for women
4. Breath alcohol level of 0.00 at in-person screening
5. Right handed
6. Explicitly be seeking help for their drinking
7. Alcohol use during the past 30 days

Exclusion Criteria:

1. History of brain injury or neurological diagnoses
2. Evidence of current psychosis
3. Past-year substance dependence other than nicotine or marijuana
4. Evidence of recent illicit drug (other than marijuana) use on a urine screen
5. Contraindications for MRI (e.g., medical devices in the body)
6. Female participants who think they may be pregnant must pass a urine pregnancy screen prior to each MRI scanning session
7. Estimated IQ < 80
8. Unable to read or speak English fluently
9. History of major alcohol withdrawal
10. Currently in treatment for alcohol use (or within the past 6 months)

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• Barbara McCrady, PhD, Principal investigator, The University of New Mexico