Modulating Neural Mechanisms of Reward Processing in Tobacco Users
Purpose
The goal of this clinical trial is to learn if a personalized, brain-scan-guided form of transcranial magnetic stimulation (TMS) works better than a standard TMS approach at changing reward-related brain activity in adults who smoke cigarettes. The main questions it aims to answer are: Does personalized TMS produce a greater change in reward-related brain activity than the standard approach? Does personalized TMS lead to a greater reduction in cravings and cigarette smoking than the standard approach? Researchers will compare personalized TMS, which targets a treatment location chosen from each participant's own brain scan, to a standard TMS approach, which targets a location based on anatomical landmarks, to see if the personalized approach produces stronger effects on brain reward activity and smoking behavior. Participants will: Complete an magnetic resonance imaging (MRI) brain scan and questionnaires about their smoking habits and mood Be randomly assigned to receive either personalized TMS or the standard TMS approach Attend 15 TMS treatment sessions over 3 weeks (Monday through Friday), including brain wave (EEG) recordings and craving check-ins before and after each session Return for follow-up visits 1 week and 1 month after finishing treatment
Condition
- Tobacco Use Disorder
Eligibility
- Eligible Ages
- Between 18 Years and 60 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Be between the ages of 18 and 60 years old - Smoke 10 or more cigarettes per day and have a carbon monoxide (CO) level greater than 10 ppm indicative of recent smoking - Have not received substance abuse treatment within the previous 30 days - Meet criteria for Tobacco Use Disorder as determined by the Mini International Neuropsychiatric Interview (MINI): meeting 4 or more of the 11 diagnostic symptoms of Tobacco Use Disorder within a 12-month period - If female, test non-pregnant - Show no evidence of focal or diffuse brain lesions on MRI - Be willing to provide informed consent - Be able to comply with protocol requirements and likely to complete all study procedures - Be motivated to quit smoking, based on a response of "very likely" or "somewhat likely" on the Motivation to Stop Scale (scores 4-7)
Exclusion Criteria
- Meeting MINI diagnostic criteria for any non-tobacco substance use disorder other than Caffeine Use Disorder, Cannabis Use Disorder - Mild, or Alcohol Use Disorder - Mild (Mild defined as meeting 2 to 3 of the 11 diagnostic symptoms within a 12-month period) - Contraindications to MRI (e.g., metal in the skull, orbital, or intracranial cavity, or claustrophobia) - Contraindication to repetitive TMS - History of autoimmune, endocrine, viral, or vascular disorders affecting the brain - History or MRI evidence of a neurological disorder causing local or diffuse brain lesions or significant physical impairment - Unstable cardiac disease, uncontrolled hypertension, severe renal or liver insufficiency, or sleep apnea - Lifetime history of major Axis I disorders as confirmed by the MINI, including bipolar affective disorder, schizophrenia, post-traumatic stress disorder, suicidal ideation, or major depression - Current use of tobacco cessation pharmacotherapies, including nicotine patches, electronic cigarettes, gum, nasal spray, inhalers, nicotine lozenges, varenicline, or bupropion - Previous treatment with TMS
Study Design
- Phase
- N/A
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Participants are randomized 1:1 to one of two parallel arms using a computerized, permuted-block procedure (block sizes of 4, 6, and 8), stratified by tobacco use disorder severity and psychiatric comorbidity status, yielding four strata. Both arms receive identical stimulation dose and schedule (10 Hz, 3,000 pulses per session, 110% resting motor threshold, 15 sessions over 3 weeks); the arms differ only in how the stimulation target is identified and whether a concurrent cognitive task is administered during stimulation. Because the two protocols are procedurally distinct in ways that are perceptible to participants and administering staff, the study is not fully blinded; however, staff who score EEG, behavioral, and clinical outcome data remain blinded to treatment assignment throughout.
- Primary Purpose
- Basic Science
- Masking
- Single (Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental PRIME TMS (Personalized Connectivity-Based Targeting) |
Participants receive 15 sessions of 10 Hz repetitive TMS over 3 weeks (Monday-Friday), delivered at 110% of resting motor threshold. The stimulation target is an individualized dorsolateral prefrontal cortex location identified from each participant's diffusion-weighted MRI as having maximal structural connectivity to the midcingulate cortex. Stimulation is delivered concurrently with a brief reward-based cognitive task performed during inter-train intervals, intended to engage the brain's reward circuitry during treatment. |
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|
Active Comparator Standard TMS (Anatomical Targeting) |
Participants receive 15 sessions of 10 Hz repetitive TMS over 3 weeks (Monday-Friday), delivered at 110% of resting motor threshold. The stimulation target is a dorsolateral prefrontal cortex location identified using standardized anatomical landmarks on structural MRI, without individualized connectivity mapping. Stimulation is delivered without a concurrent cognitive task. This approach reflects a well-established TMS protocol with a long-standing published safety and efficacy record. |
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Recruiting Locations
Newark, New Jersey 07102
More Details
- Status
- Recruiting
- Sponsor
- Rutgers, The State University of New Jersey
Detailed Description
People with tobacco use disorder often show changes in how their brain responds to rewards. A brain region involved in this process can be measured using a brain wave (EEG) signal that reflects how strongly the brain reacts to rewards. This study looks at whether a personalized form of brain stimulation can shift that signal more effectively than a standard approach. The personalized approach, Pathway-precise Reward Intervention via Midcingulate Engagement (PRIME) TMS uses each participant's own brain scan to find the stimulation location that is most strongly connected to the brain's reward center, rather than using the same general location for everyone. Stimulation is also paired with a short reward-based computer task during the session, based on the idea that engaging the brain's reward system during stimulation may strengthen its effects. The standard approach uses a fixed stimulation location based on external head landmarks and is delivered without any task. Participants are randomly assigned to one of the two approaches, similar to a coin flip, with the assignment balanced to make sure both groups have similar mixes of smoking severity and mood symptoms. Both groups receive the same number of sessions (15), on the same schedule (weekdays for 3 weeks), and the same strength and dose of stimulation. The only differences are where the stimulation is delivered and whether participants complete a task during it. Study visits include an initial screening, a brain scan to plan the intervention, a baseline visit with brain wave recording and questionnaires, the three weeks of stimulation sessions, a follow-up assessment shortly after the sessions end, and two brief check-in calls at 1 week and 1 month later. Throughout the study, the research team monitors participants closely for side effects using standardized safety checklists, and all equipment used (the stimulation device, positioning system, brain wave recorder, and MRI scanner) is already cleared by the FDA for other uses. The study will compare how much each approach changes brain reward activity, cravings, and smoking amounts, and will look at whether changes in brain activity help explain any changes in cravings or smoking behavior.