Decision Making in Chronic Pain and Alcohol Use Disorder

Study Overview
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Brief Summary
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The objective of this within-subject study is to test the effects of Episodic Future Thinking (EFT) and Low-intensity Focused Ultrasound (LIFU) interventions on the pain of subjects who have chronic pain and alcohol use disorder(s).

Detailed Description
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This study will have a within-subject design. Participants will complete a baseline session (S1) and two intervention sessions. Specifically, participants will complete two experimental conditions (episodic future thinking; EFT and low-intensity focused ultrasound; LIFU), as well as their respective control conditions (episodic recent thinking; ERT and sham ultrasound). Measures of acute and chronic pain, alcohol valuation, alcohol craving, and delay discounting will be collected after each experimental and control condition. The EFT intervention generates positive events and related cues through a researcher-administered interview-based questionnaire. Participants will be asked to think about and describe positive events that could occur at each of 6 delays in the future (i.e., 1 week, 1 month, 3 months, 1 year, 5 years, and 25 years). During the LIFU condition, participants will have an ultrasound transducer placed on their head, where brief ultrasound pulses are delivered to the desired brain area. The control condition for EFT (i.e., ERT) requires participants to think about and describe positive events that occurred at each of 64 delays in the past (e.g, last night, yesterday in the afternoon, yesterday in the evening, yesterday in the morning, yesterday in the night, and the night before). After generating these cues participants will be asked to read and consider their cues as they complete the measures again that were collected prior to the cue generation. Finally, the sham LIFU condition may be active with ultrasound blocking, or inactive so that it would not deliver stimulation. All participants will complete all conditions on three different days. First day will be the consent and baseline session, and the remaining two experimental sessions will be in a counterbalanced order. EFT and LIFU will be employed in one session, and ERT and Sham LIFU in a different session. The first and second session will be separated by 2-3 weeks, and the second and third by approximately 1 week.

Official Title
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Decision Making in Chronic Pain and Alcohol Use Disorder

Conditions
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Alcohol Use Disorder, Chronic Pain

Intervention / Treatment
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* Behavioral: Episodic Future Thinking
* Behavioral: Episodic Recent Thinking
* Device: Low-intensity Focused Ultrasound
* Device: Sham Low-intensity Focused Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 21 years old or older Report chronic pain Have sufficiently stable self-reported mental and physical health in order to complete the survey Meet DSM-V clinical criteria for alcohol use disorder (i.e., four or more criteria) Not have unmanaged medical or psychiatric conditions the survey Exclusion Criteria: Claustrophobia (scanning environment may be uncomfortable) Contraindications to MRI: including pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, or other implants. Contraindications to CT: pregnancy Active medical disorder or treatment with potential CNS effects (e.g. Alzheimer's) History of neurologic disorder (e.g. Parkinson's, Epilepsy, or Essential Tremor) History of head injury resulting in loss of consciousness for >10 minutes Failure to provide a Social Security Number or Tax ID number. This is required for tax purposes.

Ages Eligible for Study
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Minimum Age: 21 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Each participant will receive all interventions throughout the study. Their pain response will be compared after episodic future thinking (EFT) with the control, episodic recent thinking (ERT) and low-intensity focused ultrasound (LIFU) with the control, Sham LIFU.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ERT and LIFU<br>Participants will generate positive recent past events that have happened to them at several time points in the previous day (e.g., 7pm-10pm, 4pm-7pm, 1pm-4pm, 10am-1pm, and 7am-10am). During the LIFU condition, participants will have an ultrasound transducer placed on their head, where brief ultrasound pulses are delivered to the desired brain area using the imaging collected during visit 1. A small amount of ultrasound gel will be placed on the face of the single-element focused ultrasound transducer. The transducer will then be fitted on the scalp over the desired brain area and held in place with a mechanical arm. Brief pulses (0.2 to 2 seconds; duty cycle 10 - 70%; pulse repetition frequency 100 - 1000 Hz) of low-intensity (< 50 W/cm2 Isppa), sub-thermal ultrasound (0.3 - 0.5 MHz) will be delivered in order to determine the area of activation, as well as the patterns of brain activity generated. | Behavioral: Episodic Recent Thinking<br>* Participants will generate descriptions of vivid positive past events.<br>Device: Low-intensity Focused Ultrasound<br>* A transducer device will use focused ultrasound energy to neuromodulate the insular cortex. The participant's brain will be mapped based on information from the CT and MRI scans, and the transducer will deliver brief ultrasound pulses to the insular cortex.<br>* Other names: LIFU;|
| Other: EFT and Sham LIFU<br>Participants will generate positive future events they are looking forward to at several time points in the future (e.g., 2 weeks, 1 month, 3 months, 1 year, and 5 years). During Sham LIFU, the device will be set up identically as in real LIFU. However, the device will be turned off. | Behavioral: Episodic Future Thinking<br>* Participants will generate descriptions of vivid positive future events.<br>* Other names: EFT;Device: Sham Low-intensity Focused Ultrasound<br>* All of the same actions done during LIFU will be performed, but the device will be inactive.<br>* Other names: Sham LIFU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Delayed Discounting | Delay discounting tasks provide a measure of the temporal window and examine the devaluation of awards as a function of the delay to the receipt. These computerized assessments provide participants with hypothetical choices between smaller amounts of a reward available immediately and a larger amount of a reward after a range of delays (1 day-25 years). Discounting rates will be measured using adjusting amount delay discounting and minute delay discounting tasks. Change in discounting rates will be compared after different interventions are applied. | Before and after each intervention on two days separated by one week (eight times total). | 
| Changes in Acute Pain Perception | Sensitivity to acute pain will be measured using a thermal stimulus gradually reaching 50 degrees Celsius. Participants will be asked to rate the induced pain on a visual analogue scale ranging from 0 to 10, such that greater score indicates greater pain perception. The ratings from before and after each intervention will be compared. | Before and after each intervention on two days separated by one week (eight times total). | 
| Changes in Chronic Pain Severity | Pain severity will be measured using a question from the Brief Pain Inventory. This asking requires participants to rate their pain in the last 24h from 0 to 10. Greater scores indicate greater pain severity. | Before and after each intervention on two days separated by one week (eight times total). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alcohol Valuation | Intensity and elasticity of alcohol demand will be determined from an alcohol demand curve via an Alcohol Purchase Task. Change in alcohol demand will be compared within-subjects across sessions and between groups. | Before and after each intervention on two days separated by one week (eight times total). | 
| Change in Alcohol Craving | Participants will be asked to complete an alcohol urges questionnaire. This questionnaire has 8 questions. Each question has a score that ranges from 1 to 7. Questions 2 and 3 have their scores reversed. The overall score ranges from 8 to 56. Greater scores indicate greater craving. | Before and after each intervention on two days separated by one week (eight times total). |