The United States is in the midst of an opioid epidemic and lacks a range of successful interventions to reduce this public health burden. Many individuals with opioid use disorder (OUD) consume drugs to relieve physical and/or emotional pain, a pattern that may increasingly result in death. The field of addiction research lacks a comprehensive understanding of physiological and neural mechanisms instantiating this cycle of Negative Reinforcement in OUD, resulting in limited interventions that successfully promote abstinence and recovery. Given the urgency of the opioid crisis, the present review highlights faulty brain circuitry and processes associated with OUD within the context of the Three-Stage Model of Addiction (1). This model underscores Negative Reinforcement processes as crucial to the maintenance and exacerbation of chronic substance use together with Binge/Intoxication and Preoccupation/Anticipation processes. This review focuses on cross-sectional as well as longitudinal studies of relapse and treatment outcome that employ magnetic resonance imaging (MRI), functional near-infrared spectroscopy (fNIRs), brain stimulation methods, and/or electroencephalography (EEG) explored in frequency and time domains (the latter measured by event-related potentials, or ERPs). We discuss strengths and limitations of this neuroimaging work with respect to study design and individual differences that may influence interpretation of findings (e.g., opioid use chronicity/recency, comorbid symptoms, and biological sex). Lastly, we translate gaps in the OUD literature, particularly with respect to Negative Reinforcement processes, into future research directions involving operant and classical conditioning involving aversion/stress. Overall, opioid-related stimuli may lessen their hold on frontocingulate mechanisms implicated in Preoccupation/Anticipation as a function of prolonged abstinence and that degree of frontocingulate impairment may predict treatment outcome. In addition, longitudinal studies suggest that brain stimulation/drug treatments and prolonged abstinence can change brain responses during Negative Reinforcement and Preoccupation/Anticipation to reduce salience of drug cues, which may attenuate further craving and relapse. Incorporating this neuroscience-derived knowledge with the Three-Stage Model of Addiction may offer a useful plan for delineating specific neurobiological targets for OUD treatment.
Keywords: abstinence; electroencephalography; event related potentials; magnetic resonance imaging; neuroimaging; opioid use disorder; recovery.