Can neuroimaging help combat the opioid epidemic? A systematic review of clinical and pharmacological challenge fMRI studies with recommendations for future research

Abstract

The current opioid epidemic is an urgent public health problem, with enormous individual, societal, and healthcare costs. Despite effective, evidence-based treatments, there is significant individual variability in treatment responses and relapse rates are high. In addition, the neurobiology of opioid-use disorder (OUD) and its treatment is not well understood. This review synthesizes published fMRI literature relevant to OUD, with an emphasis on findings related to opioid medications and treatment, and proposes areas for further research. We conducted a systematic literature review of Medline and Psychinfo to identify (i) fMRI studies comparing OUD and control participants; (ii) studies related to medication, treatment, abstinence or withdrawal effects in OUD; and (iii) studies involving manipulation of the opioid system in healthy individuals. Following application of exclusionary criteria (e.g., insufficient sample size), 45 studies were retained comprising data from~1400 individuals. We found convergent evidence that individuals with OUD display widespread heightened neural activation to heroin cues. This pattern is potentiated by heroin, attenuated by medication-assisted treatments for opioids, predicts treatment response, and is reduced following extended abstinence. Nonetheless, there is a paucity of literature examining neural characteristics of OUD and its treatment. We discuss limitations of extant research and identify critical areas for future neuroimaging studies, including the urgent need for studies examining prescription opioid users, assessing sex differences and utilizing a wider range of clinically relevant task-based fMRI paradigms across different stages of addiction.Neuropsychopharmacology (2019) 44:259-273; https://doi.

Heroin addiction engages negative emotional learning brain circuits in rats

“…We found that conditioned heroin withdrawal motivated heroin intake and engaged brain regions that are associated with negative emotional learning, particularly extrahypothalamic and hypothalamic stress/arousal circuitries. These circuits are consistent with and extend fMRI findings in individuals with OUD on drug cue reactivity tasks (22,23). Thus, we argue that conditioned cues can maintain compulsive drug use by removing aversive states We anatomically segregated the cluster defined by the statistically significant heroin-access (ShA versus LgA) × cue (saline paired versus naloxone paired) interaction (shown in Figure 1C) into 19 ROIs using a standard rat atlas (14).…”

“…Several other regions exhibited activation patterns that were similar to those seen in the hypothalamic cluster and amygdala ( Table 1). Many of these regions have been implicated in emotional learning and are hypothesized to be dysregulated in addiction (2,22,23). These include the lateral hypothalamus, dorsomedial nucleus of the thalamus, ventrolateral thalamus, and dorsal striatum.…”

“…These include the lateral hypothalamus, dorsomedial nucleus of the thalamus, ventrolateral thalamus, and dorsal striatum. Along with the amygdala, these regions are activated by heroin cues in individuals with OUD (22,23). The extended amygdala promotes both positive and negative emotional states via its downstream connections to such areas as the lateral hypothalamus (24).…”

Acute Aerobic Exercise Ameliorates Cravings and Inhibitory Control in Heroin Addicts: Evidence From Event-Related Potentials and Frequency Bands

“…Inhibitory control impairment makes it difficult for individuals to resist the temptation of drug cues and impulsive thoughts and behaviors of intake. Moreover, neuroimaging studies have further demonstrated that, relative to healthy groups, heroin addict groups exhibit abnormal structures and lower levels of activation in brain regions related to inhibitory control during the Go/No-Go task, including impairments in the bilateral medial prefrontal gyrus, bilateral anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DPFC), left middle frontal gyrus (MFG), and left insular and bilateral inferior frontal gyrus (IFG) (Fu et al, 2008;Luijten et al, 2014;Moningka et al, 2018). Inhibitory control failure and associated brain dysfunction are key underlying factors of relapse and addiction (Su et al, 2017).…”

The Negative Affect of Protracted Opioid Abstinence: Progress and Perspectives From Rodent Models

“…Human imaging studies investigating the opioid effects on the brain have been reviewed recently (23) and discussed (24) in the context of the 3-stage addiction cycle framework (5), showing in particular that negative affect during opioid withdrawal is associated with enhanced beta power activity and increased connectivity strength between the amygdala and ventral striatum-two main reward and aversion centers. In addition, human neuroimaging was performed under conditions of protracted opioid abstinence, and these studies have been reviewed previously (25).…”