Temporal Interference Neurostimulation and Addiction

Study Overview
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Brief Summary
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This project aims to develop a line of research using new non-invasive neurostimulation technology to treat adults with opioid use disorders (OUDs). In the short term, the investigators aim to identify novel target brain regions for neurostimulation treatment and characterize their effects behaviorally and neurally. In the longer term, investigators aim to use these preliminary data to justify NIH sponsored clinical trials to apply transcranial direct current stimulation and non-invasive deep brain stimulation to these areas to partially or completely disrupt addiction.

Detailed Description
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The investigators hypothesize that temporal interference non-invasive deep brain stimulation (TI-NDBS) will be well tolerated and effective at manipulating brain activity and reducing drug cravings. The investigators will investigate whether stimulation with a mild current from temporal interference non-invasive deep brain stimulation (TI-NDBS) to the Anterior Cingulate Cortex (ACC), the anterior insula (AI), or the nucleus accumbens (NAcc) will reduce nicotine craving and seeking. The TI-NDBS is similar to the traditional transcranial direct current stimulation (tDCS), a method approved for use in a number of other studies. Other studies have shown there have been some effects of reducing craving with tDCS, however, tDCS cannot stimulate structures such as the ACC very effectively because tDCS cannot stimulate deeper brain regions. Thus, the Specific Aim ultimately will compare TI-NDBS with tDCS and sham stimulation. The study is broken up into four phases. The first two will involve device feasibility and identifying the best locations for the electrodes to be placed. In the third phase, the investigators will compare TI-NDBS with sham stimulation. In the fourth phase, the investigators will compare TI-NDBS with sham stimulation and with tDCS.

Official Title
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Temporal Interference Neurostimulation and Addiction

Conditions
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Nicotine Use Disorder, Substance Use Disorders

Intervention / Treatment
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* Device: Active TI-NDBS
* Other: Sham TI-NDBS
* Device: tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be between the ages of 18 and 40, must have at least 6th grade education, and the ability to speak and read English, must smoke at least 3/4 of a pack of cigarettes per day, must have phone with internet access. Exclusion Criteria: if they are on psychotropic medications for ADHD, other mental illness or medication for cancer, epilepsy (i.e. individuals with any history of seizure disorder), migraines, or other neurological syndromes, or AIDs (which can cause cognitive deficits (Watkins & Treisman, 2015), history of head trauma, history of cognitive impairments, metal implants in the head or under the scalp, personal experiences consistent with symptoms of psychosis (i.e. mind or body being secretly controlled, special powers, seeing or hearing things that aren't really there). Subjects will be excluded if they do not meet fMRI safety screening criteria (i.e. metal implants in their body, tattoo on head or neck, permanent jewelry, etc.) or if a participant uses an IUD for birth control they will be excluded unless the subject can document the model of the IUD and we can verify its safety for the MRI environment. Pregnancy should be self-reported, and a pregnancy test will not be administered. Participants must also weigh less than 440 lbs. History of holes bored into skull or known fissures in cranial bones Presence of pacemakers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: One group of 20 participants will receive active TI-NDBS and another group of 20 participants will receive sham TI-NDBS. A third group of 20 participants will receive traditional transcranial direct current stimulation (tDCS).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 3 Active TI-NDBS<br>Participants assigned to this condition will receive active temporal interference non-invasive deep brain stimulation. Participants will receive stimulation for 60 minutes on one day. | Device: Active TI-NDBS<br>* In the active TI-NDBS condition, subjects will receive stimulation for 60 minutes applied to the brain through scalp electrodes. There will be a maximum of 2 mA per electrode pair and no single region will receive more than 2 mA because the currents will be administered to distinct regions. At the beginning of each stimulation period, the current will increase slowly at a constant rate for 30 seconds until it reaches the appropriate intensity. At the end of the stimulation, the current will decrease slowly for 30 seconds until it reaches zero.<br>* Other names: Temporal Interference Non-invasive Deep Brain Stimulation;|
| Sham Comparator: Phase 3 Sham TI-NDBS<br>Participants assigned to this condition will receive sham temporal interference non-invasive deep brain stimulation, in which they will have electrodes attached to the scalp but the device is only turned on for a few seconds. | Other: Sham TI-NDBS<br>* This is the control condition in which participants will receive sham stimulation for 60 minutes.<br>|
| Active Comparator: Phase 4 Traditional tDCS<br>Participants assigned to this condition will receive traditional transcranial direct current stimulation for 60 minutes for 5 days. | Device: tDCS<br>* This is a well established method of brain stimulation and will be used to compare against the efficacy of TI-NDBS in the reduction of nicotine craving and inhalation. Participants will receive stimulation for 60 minutes.<br>|
| Experimental: Phase 4 TI-NDBS<br>Participants assigned to this condition will receive active temporal interference non-invasive deep brain stimulation for 60 minutes for 5 days and will be compared to sham stimulation and tDCS. | Device: Active TI-NDBS<br>* In the active TI-NDBS condition, subjects will receive stimulation for 60 minutes applied to the brain through scalp electrodes. There will be a maximum of 2 mA per electrode pair and no single region will receive more than 2 mA because the currents will be administered to distinct regions. At the beginning of each stimulation period, the current will increase slowly at a constant rate for 30 seconds until it reaches the appropriate intensity. At the end of the stimulation, the current will decrease slowly for 30 seconds until it reaches zero.<br>* Other names: Temporal Interference Non-invasive Deep Brain Stimulation;|
| Sham Comparator: Phase 4 Sham stimulation<br>Participants assigned to this condition will receive sham temporal interference non-invasive deep brain stimulation, in which they will have electrodes attached to the scalp but the device is only turned on for a few seconds. Participants will be in the scanner for 60 minutes for 5 days. This will be used as the control condition and compared with TI-NDBS and tDCS. | Other: Sham TI-NDBS<br>* This is the control condition in which participants will receive sham stimulation for 60 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Nicotine craving | The investigators predict that TI-NDBS will outperform sham stimulation at an overall change in smoking and cigarette craving, which in turn will outperform sham stimulation. The investigators will sum the total inhaled nicotine vapor volume in liters over the 60 minute session and perform pairwise t-tests to determine if total drug intake is lower with TI-NDBS vs tDCS. Also, the investigators will average the self reported craving levels on a Likert scale across each subject during the 60 minute session, and the investigators will perform pairwise tests to determine if stimulation lowers self reported craving. | Within the first year of testing TI-NDBS in nicotine smokers. | 
| Change in Nicotine craving due to TI-NDBS compared to tDCS | The investigators predict that TI-NDBS will outperform tDCS at an overall change in smoking and cigarette craving, which in turn will outperform sham stimulation. The investigators will sum the total inhaled nicotine vapor volume in liters over the 60 minute session and perform pairwise t-tests to determine if total drug intake is lower with one of the stimulation groups vs. sham. Also, the investigators will average the self reported craving levels on a Likert scale across each subject during the 60 minute session, and the investigators will perform pairwise tests to determine if stimulation lowers self reported craving. | 1 year after the first primary outcome. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine Addiction, Non-invasive deep brain stimulation, Substance Use Disorders