Identify the Optimal TMS Pulse Protocol to Modulate Reward Activity

The design is primarily a randomized control-trial design (2 sessions), comparing the effects excitatory and inhibitory TMS protocols applied to a prefrontal TMS target on reward processing in smokers. Eligible smokers will be invited to attend two experimental sessions over a 1-month period, and asked to abstain from smoking 4 hrs prior to each session. For Sessions A and B, participants will be asked to provide their consent, CO levels and complete the TCQ. Compliance with the 4-hour abstinence period will be defined as breath CO less than 13 ppm. Participants will then be randomly selected to participate in Condition 1a or Condition 1b. All procedures between the two conditions will be identical except for the contrasting TMS protocols (Condition 1a: excitatory protocols, Condition 1b: inhibitory protocols) and the rewards presented in the T-maze task (Condition 1a: monetary rewards, Condition 1b: monetary rewards with cigarette cues). To streamline these studies, the left DLPFC target will be based on conventional DLPFC targeting methods (electrode position F3). For Condition 1a, the protocol administered in Session A and B will be randomized so that participants will either receive 3600 pulses of 10-Hz TMS or 3600 pulses of cTBS. For each session, participants will first engage in one block of T-maze trials (100 trials: Baseline measure). In Condition 1a, participants are told that the reward stimulus indicated 5 cents and that the presentation of the no-reward stimulus indicated the alley was empty (0 cents). Following this block of trials, participants will either receive 10-Hz TMS or cTBS over the predefined DLPFC target (F3), and then asked to complete 3 additional Blocks of the T-maze (300 trials: post-TMS). Immediately after participants complete the T-maze, subjects will be asked to complete the PST and TCQ. At the end of the Session A, participants will complete Session B on a separate day (all procedures identical as Session A). Session A and Session B will be separated by at least 2 days to minimize carryover effects. For Condition 1b, the protocol administered in Session A and B will be randomized so that participants will either receive 600 or 1200 pulses of iTBS. For each session, participants will first engage in one block of T-maze trials (100 trials: Baseline). In Condition 1b, participants are told that the reward stimulus indicated 5 cents and that the presentation of the no-reward stimulus indicated the alley was empty (0 cents). Each reward and no-reward stimulus will be paired with a cigarette cue. Following this block of trials, participants will either receive 600 or 1200 pulses of iTBS over the predefined DLPFC target (electrode F3), and then asked to complete 3 additional Blocks of the T-maze (300 trials: Post-TMS). Immediately after participants complete the T-maze, subjects will be asked to complete the PST and the TCQ. At the end of the Session A, participants will complete Session B on a separate day (all procedures identical as Session A). Session A and Session B will be separated by at least 2 days to minimize carryover effects.

Inclusion criteria

• Nicotine dependent individuals (according to the Alcohol, Smoking and Substance Involvement Screening Test nicotine dependence score).
• Be between the ages of 18 and 55 years old.
• Not received substance abuse treatment within the previous 30 days.
• Be in stable mental and physical health.
• If female, test non-pregnant.
• 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

• 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.
• Life time history of mental disorders such as: Bipolar Affective disorder (BPAD), Schizophrenia, Post-traumatic Stress disorder (PTSD) or Dementia or Major Depression.
• uninterruptable central nervous system medication