Outcome Inference in the Sensory Preconditioning Task in Opioid-Use Disorder

Drug Addiction, Opioid-Related Disorders

Addiction, Orbitofrontal Cortex, Associative Learning, Implicit Learning, Natural History

Background: People with addictions often find it hard to choose the long-term benefits of abstinence over the short-term effects of using drugs. Researchers think this is partly due to parts of the brain involved in certain types of learning and decision-making. Researchers want to test these basic functions using a simple task with pictures and odors. Objective: To see if performance in a learning task differs between people who have opioid-use disorder and people who don t. Eligibility: Adults 21-60 years old who are willing to fast for at least 6 hours and smell food odors. Those with an opioid-use disorder must either not use for at least 3 weeks or be in treatment. Design: Participants will have 1 visit that will take up to 5 hours. Before the visit, participants will be asked to not eat or drink anything except water for at least 6 hours. At the visit, participants will be checked for signs of intoxication. Participants will give urine and breath samples. Participants will have tests of learning and behavior. They will look at shapes on a computer screen. The shapes will be paired with different food odors. The odors will come from a sterile tube placed under the nose. Participants will have their breathing monitored with a belt around the upper abdomen. About 30 days and 60 days later, participants will be called and asked about their drug use over the past 30 days.

Background. People with substance-use disorders may have difficulty guiding their behavior on the basis of not-yet-experienced outcomes such as long-term effects of substance use. Use of mental inferences about future outcomes can be tested in a relatively simple laboratory task called sensory preconditioning. Objective. To test whether sensory-preconditioning performance is worse in people with opioid use disorder (OUD) than in healthy, demographically matched controls. To increase generalizability, we will examine OUD participants who are in agonist treatment (abstinent or not) and OUD participants who are abstinent but not in treatment. We do not have a hypothesis about differences between those two groups, but we hypothesize that among agonist-treated OUD participants, performance will correlate with degree of abstinence. Participant population. We will enroll 3 groups of men and women: (1) history of OUD, but abstinent for at least 3 weeks and not in agonist treatment, (2) OUD being treated with an agonist (buprenorphine or methadone), (3) no history of a substance-use disorder (except nicotine, for matching purposes) and not using any drug for nonmedical purposes. Experimental design. Between-groups cross-sectional single-session laboratory study, with telephone follow-up at 30 and 60 days. Methods. Each participant will participate in a sensory preconditioning task conducted in a single session. The task uses food odors delivered via nasal cannula and paired with visual cues on a computer screen. There are three phases: (1) Preconditioning, in which 2 pairs of visual cues (A+B, C+D) are shown on the computer screen; participants should acquire automatic associations between A+B and between C+D. (2) Conditioning, in which participants learn associations between the second cue of each pair (B and D) and either a sweet odor (B1), a savory odor (B2), or no odor (D); and (3) Probe Test, in which participants predict whether a visual cue will be paired with the sweet odor, the savory odor, or no odor, by pressing a left, middle, or right button. No odors are actually delivered in the probe test. The test of inference-guided behavior is the ability to associate visual cues A and C with an odor despite their never having been directly paired with an odor. In telephone follow-up at 30 and 60 days, participants will be asked to report drug use and associated problems since the session or follow-up call. Primary outcome measures. (1) Value-based outcome inference as measured using responding to cues A minus C in the probe test. It is defined as the percentage of trials in which behavioral responses indicate a prediction of any odorant (sweet or savory), independent of whether this prediction is correct. Responding to cues B minus D will be used as a covariate to control for differences in olfactory acuity and non-inference-based task performance. Secondary outcome measures. (1) The percentage of trials in which the odor prediction is correct. (2) Response latency per cue type. (3) Amplitude and (4) latency of respiratory (sniff) responses per cue type. (5) Acquisition (% responding to B minus D in the last run of conditioning) during the training portion of the inferencing task. (6) Drug use and associated problems at follow-up.

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