Interdisciplinary Initiatives Program Round 10 - 2020
Kim Butts Pauly, Radiology
Casey Halpern, Neurosurgery
Xiaoke Chen, Biology
Addiction is major public health challenge in the US. It affects millions of people with enormous societal burden. The costs include compromised physical and mental health, loss of productivity, reduced quality of life, increased crime and violence, abuse and neglect of children, and health care costs. For tobacco use as an example, it costs >$300 billion annually for patients who die from smoking, and at least 1.5 million people live with serious smoking-related illnesses. Opioid addition in the US is well known. Unfortunately, most attempts to quit addictive substances fail. In recent years, we have learned how brain activity changes lead to addiction. Addictive drugs can bind to ubiquitously distributed receptors and trigger the release of dopamine from the ventral tegmental area (VTA), the reward center in the midbrain where dopamine is produced. Addictive drugs appear to make the neurons in VTA more excitable overall. In addition, limbic structures that receive VTA projections such as the striatum and ventromedial prefrontal cortex (vmPFC) constitute the mesocorticolimbic circuit that has repeatedly been found to mediate impulsive decision-making particularly during a vulnerable withdrawal state. These circuits constitute the initiator, enforcement, and maintenance of addiction, providing the opportunity to develop new treatments targeting the brain for treating addiction. We will develop a non-pharmaceutical and non-surgical approach, instead based on transcranial ultrasound (TUS), for treating addiction that is non-invasive and safe. TUS will provide deep penetration and a steerable high spatiotemporal resolution focus. We will test whether inhibition of neural activity in PVT by TUS eliminates withdrawal symptoms, and whether closed-loop modulation on NAc reduces drug intake. In addition, testing will also include TUS in VTA and vmPFC. We will treat the addicted mice by modulating neural circuits across various brain regions and investigate the mechanisms involved.