The goal of this clinical trial is to to inhibit the dorsal anterior insula (dAI) with low intensity focused ultrasound (LIFU) to determine the causal role for the dAI in smoking cue induced craving in individuals with tobacco use disorder (TUD); smoking cue induced craving is a clinically important behavior which has been associated with the severity of nicotine addiction. The main question\[s\] it aims to answer are:
* the safety and tolerability of dAI LIFU compared to sham stimulation in individuals with TUD * the effects of LIFU vs sham to left dAI functional magnetic resonance imaging (fMRI) BOLD activity and craving in response to smoking cue exposure.
Participants will undergo anatomical MRI, neurological assessment, clinical assessment and patient query to assess the safety and tolerability of LIFU vs sham.
Participants will undergo functional magnetic resonance imaging where we will measure the effect of LIFU vs sham on 1) dAI blood-oxygen-level-dependent (BOLD) activation in response to smoking (compared to neutral) cue exposure and 2) cue-induced craving in individuals with TUD. Each participant will receive LIFU and sham stimulation.
Male and female veterans aged 18-75 years
Meet the Diagnostic and Statistical Manual, Fifth edition (DSM-5) criteria for current TUD (moderate to severe) as diagnosed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.
Currently smoking > 10 cigarettes per day with no period of abstinence > 3 months in the last year
Current use of tobacco in last year is limited to cigarettes
Not under current treatment for smoking cessation.
No history of head injury, seizures, neurologic disorders including cerebrovascular disease, multiple sclerosis, or neurodegenerative diseases or major medical illness
Current substance use disorder for a psychoactive substance (except nicotine)
DSM-5 psychiatric disorder requiring current treatment
Crossover
low intensity focused ultrasound (LIFU)
DeviceLow-intensity focused ultrasound (LIFU) provides an energy source with millimeter resolution that can be focused anywhere in the brain safely and effectively for non-invasive and transient neuromodulation. LIFU is an important advance and of great significance for brain-mapping efforts, diagnostics, and therapies in neuroscience and particularly promising for addiction therapy as it provides unprecedented non-surgical access to the brain regardless of depth. Much lower intensities of focused ultrasound (LIFU) are used so that tissue damage does not occur, but neural activity can be modulated. LIFU utilizes acoustic energy at much lower levels to affect tissue by mechanical effects.
Incidence of Treatment-Emergent Adverse Events
number of adverse events
Smoking cue-induced craving
numerical craving rating scale Score Range: 0-100 (Higher score meaning worse outcome) 0 = No thoughts of Craving 100 = All of your thoughts of craving
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