We planned to enroll more participants but we could not recruit more participants. In addition, the covid-19 pandemic made the recruitment worse than the previous years.

Cigarette smoking causes significant morbidity and mortality in the United States. Smoking cessation is difficult, with the average smoker attempting to quit five times before permanent success. Moreover, the majority of smoking quit attempts result in relapse. Brain stimulation for smoke cessation is an exciting new area that builds on advancing neuroscience knowledge concerning the functional neurocircuitry of addiction. Cortical stimulation can now be performed non-invasively by transcranial magnetic stimulation (TMS). Several studies have shown that TMS can reduce cue-elicited craving in smokers. Previous research by group has shown that a single session of 15 minutes high frequency (10 Hz) repetitive TMS (rTMS) at 100% motor threshold over the left dorsal lateral prefrontal cortex (DLPFC) can reduce cue-induced craving compared to sham TMS. However, the mechanism by which craving is reduced by rTMS is poorly understood both at behavioral and neural levels. Neuroimaging studies in nicotine dependence have revealed cue-related responses in numerous brain areas, including frontal, parietal cortices and subcortical areas. Recently functional magnetic resonance imaging (fMRI) studies by the group have shown that cue-induced craving induced brain activation in ventral medial prefrontal cortex (VMPFC), including medial frontal, orbital frontal and anterior cingulate. This Chair Research Development Fund (CRDF) pilot proposal will integrate two new techniques- TMS and fMRI to investigate DLPFC-VMPFC pathway in smokers. Using double-masked methods investigators hypothesize that cue-induced exposure will induce brain activity in VMPFC, and 15 minutes rTMS over DLPFC will reduce cue-induced craving through modulating DLPFC-VMPFC pathway (increased activity DLPFC and decreased activity VMPFC).

Inclusion Criteria:

• Smoke 10 or more cigarettes per day and have a carbon monoxide (CO) level > 10 ppm indicative of recent smoking.
• Not received substance abuse treatment within the previous 30 days.
• Meet criteria for nicotine dependence as determined by the FTND.
• Be in stable mental and physical health.
• If female, test non-pregnant and use adequate birth control.
• No evidence of focal or diffuse brain lesion on MRI.
• Be willing to provide informed consent.
• Be able to comply with protocol requirements and likely to complete all study procedures.

Exclusion Criteria:

• Current dependence, defined by DSM-V criteria, on any psychoactive substances other than nicotine or caffeine.
• Contraindication to MRI (e.g., presence of metal in the skull, orbits or intracranial cavity, claustrophobia).
• Contraindication to rTMS (history of neurological disorder or seizure, increased intracranial pressure, brain surgery, or head trauma with loss of consciousness for > 15 minutes, implanted electronic device, metal in the head, or pregnancy).
• History of autoimmune, endocrine, viral, or vascular disorder 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.
• Life time history of major Axis I disorders such as: Bipolar Affective disorder (BPAD), Schizophrenia, Post-traumatic Stress disorder (PTSD) or Dementia or Major Depression.
• Self report of >21 standard alcohol drinks per week in any week in the 30 days prior to screening.
• Other forms of nicotine delivery, such as nicotine patch, electronic cigarettes

7 days.

During TMS treatment sessions, participants can feel pain, unpleasantness, or headache.