RTMS Targets Neural Circuits for Smoking Cessation

Cigarette smoking is a significant public health concern. Transcranial magnetic stimulation (TMS) is a non-invasive form of brain stimulation that has already displayed remarkable potential for producing novel, non-pharmacological interventions for depression and cigarette smokers. In this study, investigators will use brain MRI to guide TMS therapy for smoking cessation.

Smoking cessation is difficult, despite the demonstrated efficacy of several pharmacotherapeutic agents and cognitive behavioral therapies. This may be due to imbalanced neuronal circuits, including elevated functional connectivity in the drive-reward circuit (medial orbital frontal cortex \[mOFC\] to nucleus accumbens \[NAc\]) and decreased functional connectivity in the executive control circuit (dorsolateral prefrontal cortex\[ DLPFC\] to NAc). Repetitive transcranial magnetic stimulation (rTMS) is a new class of therapeutics that has already displayed remarkable potential for producing novel, non-pharmacological interventions for neuropsychiatric disorders. Previous studies have reported that rTMS decreased cue craving, reduced cigarette consumption, and increased smoking quit rate in tobacco use disorders(TUDs). However, the treatment parameters and exact mechanism for rTMS increasing smoking quit rate need further refinement. The goal of this study is to develop a circuit-based precision rTMS therapy for smoking cessation further. In the 3-year UH3 phase, investigators will conduct a randomized, double-blinded, sham-controlled trial of rTMS in 64 treatment-seeking tobacco use disorders (TUDs) smokers. Participants will be randomized to one of two conditions:

1. Sham rTMS, or 2. Active 10 Hz personalized-fMRI and E-field-modeling guided rTMS over the left dorsolateral prefrontal cortex (DLPFC). All participants will receive 20 daily sessions of rTMS over 4 weeks. Functional MRI scans will be performed prior to the first TMS treatment, after TMS session 10, and after the last TMS treatment session. All participants will have a one-week follow-up and 4 monthly follow-up visits (after the last TMS session 1 week, 1 month, 2 months, 3 months, and 4 months) after the last TMS session.

Eligibility Criteria:
Inclusion Criteria

* Be between the ages of 22 and 70 years old.
* Smoke 10 or more cigarettes per day and have a carbon monoxide (CO) level \&gt; 10 ppm indicative of recent smoking.
* Have not received substance abuse treatment within the previous 30 days.
* Meet the criteria for tobacco use disorder as determined by DSM-5.
* Be in stable mental and physical health.
* If female, test non-pregnant and use adequate birth control.
* 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 responses of "very likely," or "somewhat likely" in the motivation questionnaire).

Exclusion Criteria

* Current moderate to severe substance use of any psychoactive substances other than nicotine or caffeine, as defined by DSM-V criteria.
* Contraindications to MRI (e.g., presence of metal in the skull, orbital or intracranial cavity, or having claustrophobia).
* Contraindication to rTMS.
* History of autoimmune, endocrine, viral, or vascular disorders affecting the brain.
* History or MRI evidence of neurological disorder that would lead to 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 such as: bipolar affective disorder (BPAD), schizophrenia, post-traumatic stress disorder (PTSD), dementia, suicidal ideation or major depression.
* Self-report of \&gt;21 standard alcohol drinks per week in any week in the 30 days prior to screening.
* Use of other forms of nicotine delivery, such as nicotine patches, electronic cigarettes, gum, nasal spray, inhalers, and nicotine lozenges.
* Use of other tobacco products, including cigars, cigarillos, chew, snuff, and pouches/snus.
* Previous treatment with TMS.