Brain-to-brain neurofeedback during naturalistic dynamic stimuli to reduce craving in heroin addiction

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The opioid epidemic remains a major public health crisis in the US, with relapse rates and overdose-related fatalities continuing to rise. However, the mechanistic explorations of viable interventions in individuals with opioid use disorder have been particularly scarce. Here we will explore a novel brain-based intervention to decrease craving in individuals with heroin use disorder (iHUD) in early treatment. A core characteristic of drug addiction is an enhanced reactivity to drug related cues and reduced processing of other reinforcers in the natural environment, as reliably observed across numerous brain networks and associated with enhanced craving (a predictor of drug use outside the lab). Our recent studies in iHUD suggest that this brain-behavior cue-induced biased pattern improves with abstinence/treatment. Therefore, we will test whether preemptively changing such neural cue reactivity could expedite the recovery process as measured with reduced drug craving. Specifically, we hypothesize that training can help iHUD achieve an intentional modulation of their cue reactivity signal. Using one’s own brain signal, real-time fMRI neurofeedback (rt-fMRI NF) allows participants to volitionally modulate brain activity in targeted brain regions shown in smokers and heavy alcohol drinkers to be effective in reducing drug cue neural reactivity, as associated with abstinence/decreases in craving. However, the permeability of this approach is not uniform. Here for the first time, we will test whether the NF effect can be enhanced by using the signal derived from the brains of others (i.e., brain-to-brain neural transmission). Specifically, our first aim in this cutting-edge exploratory application is to identify the brain regions that distinguish between early (abstinent for <1 month) as compared to later (abstinent for >3 months) time-in-treatment in iHUD. Our second aim is to use the unique multivariate neural patterns derived later in treatment as NF provided to a newly recruited sample of iHUD in early treatment, with the goal of increasing neuronal coupling between both groups. To increase ecological validity and better approximate actual real-world experiences in iHUD, the stimulus is a dynamic, narrative-based, and context-rich movie. Our working hypothesis is that, as compared to iHUD in early treatment where drug cue reactivity is more automatic and harder to control (impacting non drug processing), recovering individuals are better able to regulate it allowing them to reduce craving (and curtail, or entirely eliminate, drug- seeking) even in potent drug-related situations. Therefore, during rt-fMRI NF, we expect greater recovery (and lower cue-induced craving) in the new sample of iHUD early in treatment who show the most neural coupling/alignment with the neural patterns of those in later recovery. In short, in this innovative R21 proposal we will answer the following question: Can the neural patterns of addicted individuals in later recovery be used to provide scaffolding for the nascent recovery process early in treatment, helping to reduce craving? Results of this proof-of-concept study can be used in later longitudinal studies to develop real-time NF-based training to improve outcomes in iHUD as generalizable to other substance use disorders.