Preliminary Results for Low Intensity Focused Ultrasound for Tobacco Use Disorder: High Resolution Targeting of the Human Insula

Tobacco Use Disorder (TUD) is one of the leading causes of preventable death in the world. Most smokers have a strong desire to quit smoking, but most attempts at such fail within a week. Current treatments involve pharmacotherapies such as nicotine replacement therapy (NRT), bupropion, and varenicline, however the efficacy of these treatments is limited. Thus, there remains a need for safe and effective treatments for TUD. Several neurocircuits have been associated with TUD and other addictions, a key region being the insula, specifically the anterior insular cortex (AIC). Non-invasive neuromodulation intervention such as transcranial magnetic stimulation (TMS) has been shown to be a promising treatment for TUD treatment, leading to FDA clearance in 2008 [1]. However, deep brain stimulation using TMS has several drawbacks in terms of spatial resolution and attenuation in deep brain regions. The AIC is both small and deep in the brain. Low Intensity Focused Ultrasound (LIFU) can selectively target the insula at a high spatial resolution and with less attenuation compared to TMS.After a complete description of the study to the subjects, written informed consent was obtained which was approved by the DC Veterans Affairs Medical Center Institutional Review Board. Study questionnaires were collected and managed using REDCap electronic data capture tools hosted at the Department of Veterans Affairs. This study examines the safety and tolerability of LIFU in individuals with TUD and the effect of LIFU to the left AIC fMRI on blood oxygen-level-dependent (BOLD) activity using a within-subject, sham controlled design. Participants completed 4 study visits, during 3 of which they receive LIFU. This report contains preliminary data and results for the tolerability and online/offline effects of LIFU to the AIC from 7 individuals taken from the second study session, and fMRI results from 5 of those individuals who completed all four sessions. Structural MRI and CT scans were done during the first session for acoustic modeling. The second session was designed to assess the safety and tolerability of LIFU based on physiological signals, emotional and cognitive tasks, and nicotine craving. The third and fourth sessions were designed to evaluate the effect of LIFU on the activation in key regions of the brain in response to smoking cues. These preliminary results show no statistically significant difference between baseline, during stimulation, and after stimulation epochs for the physiological (F(2,11.41) = 1.46, p=0.273) and clinical measurements (F(2,12)=0.04, p=0.965) recorded in this study during the second session. Additionally, none of the seven participants reported any lasting adverse side effects immediately after stimulation, an hour post stimulation, nor 24 hours post-stimulation. These results also show a significant effect of LIFU versus sham in the 5 participants in BOLD signal response (p (uncorrected) = 0.005, minimum cluster size = 10) to smoking cues in several brain regions.

Author

• Lindeman, Evan

Language

• English

Keyword

• Focused ultrasound
• Neuromodulation
• Anterior Insula
• Tobacco Use Disorder

Date created

• 2025

Type of Work

• Master's Thesis

License

• All rights reserved

Rights statement

• In Copyright

GW Unit

• Biomedical Engineering

Degree

• M.S.

Advisor

• Lee, Mary R
• Zderic, Vesna

Committee Member(s)

• Li, Zhenyu
• Kay, Matthew
• Zderic, Vesna
• Lee, Mary R

Persistent URL

•  https://scholarspace.library.gwu.edu/etd/765372227