Projects

Characterize and control neural circuits critical to addictive choice in animal models

(Chen, Deisseroth, Giocomo, Halpern, Knutson, Malenka, Soh)

Lack of understanding of how addiction develops and is maintained presents a major challenge in prevention and treatment. Researchers currently believe that powerful associations are formed between drug-evoked experiences and proximal environmental cues. Once formed, these cues develop powerful motivational pulls of their own and can encourage an early-stage user to progress in their addiction as well as trigger relapse by an addicted individual after a period of abstinence. It is therefore critical to understand which neural circuits mediate drug cue associations, how these neural circuits change as a consequence of drug exposure, how the drug experience becomes stamped into memory, and how these processes could be altered for therapeutic benefit. To address these questions, we aim to:

• Characterize neural circuits critical to learning drug associations and inducing relapse in rodent models.
• Alter those circuits to demonstrate their causal importance for drug addiction and relapse.
• Translate these findings to human neuroimaging and therapeutic interventions.

Identify neural predictors of drug relapse in humans

(David, Humphreys, Knutson, Padula, Williams)

Our inability to predict relapse after treatment, and even to reliably track progress during care represents a fundamental barrier to recovery for over two million patients who seek treatment each year for addiction. Although the cessation of drug use can be easily monitored during a patient’s treatment in a residential facility, this measure adds little predictive value due to drug-induced lasting changes in brain circuity that persist beyond acute use or intoxication. In fact, clinicians presently have no way of predicting who is most at risk of relapse after leaving treatment, and therefore who might benefit from more or different care. In this project, we aim to:

• Identify reliable neural markers of change in patients undergoing addiction treatment using neuroimaging.
• Characterize neural predictors of relapse in various treatment-seeking individuals with disorders of addiction (e.g., to stimulants, alcohol, nicotine, and gambling).

Modify neural markers to forestall relapse to drug use in humans

(Durazzo, Knutson, Padula, Williams)

Identification of reliable neural markers for relapse opens the possibility of developing clearly targeted interventions. Although many different therapeutic regimens have been used to treat addiction, no standard framework exists for predicting or comparing the effects of different treatments. Informed by characterization of neural predictors of relapse in both animal research and human research (Aims 1-2), this aim will test several interventions (repetitive transcranial magnetic stimulation, FMRI neurofeedback, cognitive reappraisal, and drug administration). We specifically aim to:

• Test the effects of different interventions (i.e., rTMS, fMRI neurofeedback, cognitive reappraisal, drug administration) on reward cue-elicited neural activity in healthy individuals.
• Leverage the most effective intervention to reduce drug-cue elicited brain activity in addicted patients, and track relapse to assess efficacy.
• Enhance understanding of the mechanisms of addiction by exploiting treatment-induced change in its hypothesized neural underpinnings.
• Extend effective interventions from individuals with stimulant abuse to individuals with other types of addiction (e.g., alcohol, opioids, and nicotine).

Translate addiction science findings into actionable policy recommendations

(Humphreys, Lembke, MacCoun, Williams)

Addictive choice causes enormous damage not only to individuals, but also to societies—including families, communities, and nations. Public policies designed to ameliorate this damage may lack efficacy or even exacerbate these problems (for example, by contributing to the over-incarceration of drug users, poor access to treatment, and the ineffective regulation of industries whose business model relies on addictive consumption). A key reason for the inefficacy of many policies designed to manage addiction is that they rely upon problematic conceptions of addictive behavior (notably, moral framings of addiction that emphasize wickedness and retribution, and rational-choice framings that treat addictive products like any other market commodity). It is increasingly clear that addictive behavior emerges from the reciprocal effects of enduring impairments in the brain, together with environments that make highly rewarding substances more appealing, affordable, visible, and easy to obtain for a progressively larger proportion of the population. To address this problem, we aim to:

• Create and convene a policy network of NeuroChoice addiction scientists and elected/appointed officials (e.g., State Representatives, mayors, judges).
• Collaborate with policy makers to bring neuroscience to bear on drug policy making and to better inform scientists of the nature and needs of the public policy world.