Towards Treatment of the Complex Patient: Investigations of Low-intensity Focused Ultrasound

Opioid use disorder with co-morbid chronic pain and anxiety is a clinical triad associated with the highest risk of opiate overdose deaths. Co-occurrence of these three disorders amplifies symptoms of each and results in poorer treatment outcomes. There are shared neurobiological substrates for these disorders such as reward processing and stress response. The anterior insula (AI) is a brain region involved in these processes as well as in clinical disorder of pain, addiction, and anxiety. The AI is upregulated in pain, addiction and anxiety disorders and is therefore a potential therapeutic target for neuromodulation. Low-intensity focused ultrasound (LIFU) is a noninvasive method to inhibit cortical and deep brain regions. LIFU can reach deep brain regions such as the AI with spatial specificity, unlike traditional noninvasive neuromodulation methods which lack spatial specificity and depth penetration. LIFU can selectively target the insula and its subregions and provides a potentially transformative method to reduce symptoms of pain, opiate craving, and anxiety in a complex patient population such as co-morbid chronic pain, anxiety, and opioid use disorder. In this study, the investigators will administer one session of inhibitory LIFU to the AI in individuals with opiate use disorder, chronic back pain, and anxiety disorders (generalized anxiety disorder, post-traumatic stress disorder, or social anxiety disorder)]. The aim of this phase of the study is to establish that LIFU vs sham LIFU to AI is safe and well tolerated as measured by adverse events, clinical evaluation and repeated structural brain magnetic resonance imaging scans. The investigators will also gather preliminary data on the effect of LIFU to AI on opiate cue-induced craving and laboratory measures of central sensitization(CS) which occurs with pain chronicity such as temporal summation of pain and conditioned pain modulation. There is a need for improved treatments for complex patients such as co-morbid chronic back pain, anxiety, and opioid use disorder beyond combining treatments for each disorder. LIFU provides an ability to transiently and selectively inhibit AI to determine its causal role in co-morbid chronic back pain, anxiety, and opioid use disorder symptoms which then may lead to improved treatments for this clinical triad which is associated with poor treatment outcomes.