Temporal interference methods for addiction treatment - Project summary/abstract (30 lines max) Substance use disorders (SUDs) remain difficult to treat, but recent studies have shown remarkable, effortless loss of addiction to both opioids and alcohol with invasive deep brain stimulation of the nucleus accumbens. Likewise, disruption of the anterior insula has also led to spontaneous, effortless loss of addiction. While highly effective, deep brain stimulation as a treatment for addiction is out of reach for the general population due to the expense and risk of the brain surgery involved. If similar stimulation could be carried out non-invasively, it could potentially make more effective treatment for a variety of SUDs broadly accessible, with profound individual and public health implications. A new technology called temporal interference (TI) electrical neurostimulation may provide such a means of non-invasive stimulation of deep brain regions, but it has not yet been tested for efficacy in clinical samples. We recently provided a first step by demonstrating that TI can effectively activate the nucleus accumbens as measured by simultaneous fMRI BOLD imaging. With the technique now demonstrated, we propose a preliminary clinical trial to test the effects of 60 minutes of TI stimulation on the nucleus accumbens and anterior insula on nicotine craving and use, both during TI stimulation and for one week following, using ecological momentary assessment methods. Heavy smokers and vape users will be recruited and will abstain from nicotine prior to stimulation. Subjects will be randomized into three groups: nucleus accumbens, anterior insula, and sham control groups. They will receive TI stimulation (or sham) for 60 minutes with self-reported cravings every 10 minutes and each day for one week after. Our existing custom vape device will measure the volume of inhaled vapor to identify changes in actual nicotine use during TI stimulation. All subjects will complete a set of questionnaires assessing their level of nicotine dependence, their comfort during the stimulation experience, their cognitive abilities before and after stimulation, and any changes in emotion and motivation before vs. after the stimulation. We will analyze the results to identify decreases in nicotine craving and/or nicotine vapor inhalation during stimulation of nucleus accumbens vs. sham and anterior insula vs. sham, and directly between nucleus accumbens and anterior insula stimulation. Furthermore, we will identify the duration of such effects by running similar statistical tests on the self-reported craving and nicotine use over the following 7 days. We will also assess safety and tolerability, which were good in our pilot subjects. Positive results in this clinical trial will have profound implications, as the TI technology can be mass produced and used as an “electroceutical”, with equipment potentially similar in size and cost to a common cell phone.
