QuitFast: Evaluating Transcranial Magnetic Stimulation as a Tool to Reduce Smoking Directly Following a Quit Attempt
Condition: Smoking; Smoking Cessation; Craving; Addiction; Addiction Nicotine; Nicotine Dependence; Cigarette Smoking
MeSH terms: Tobacco Use Disorder; Behavior, Addictive
Study type: Interventional

Summary: 
      Cigarette smoking constitutes the greatest preventable cause of mortality and morbidity in
      the US. The most critical period for long term success of smoking cessation appears to be in
      the first 7 days after the quit date. A metaanalysis of 3 pharmacotherapy trials revealed
      that abstinence during the first 7 days was the strongest predictor of 6 month outcomes
      (n=1649; Odds ratio: 1.4, P <0.0001; Ashare et al. 2013). Prodigious relapse rates during
      this first week of smoking cessation are likely due to behavioral and neurobiological factors
      that contribute to high cue-associated craving and low executive control over smoking. The
      long term goal of the research is to develop evidence-based transcranial magnetic stimulation
      protocols to facilitate abstinence during this critical period.
    

Detailed description: 
      The competing neurobehavioral decision systems (CNDS) theory posits that in addiction, choice
      results from a regulatory imbalance between two decision systems (impulsive and executive).
      These behavioral systems are functionally linked to two discrete frontal-striatal circuits
      which regulate limbic and executive control. Modulating these competing neural circuits (e.g.
      either dampening the limbic/impulsive system or amplifying the executive control system), may
      render smokers less vulnerable to factors associated with relapse. The scientific premise for
      the proposed research is that direct modulation of these neural circuits will induce changes
      in cigarette valuation and brain reactivity to smoking cues.

      However, the relative efficacy of targeting one or the other systems is unknown. To address
      this gap the investigators will target the two components derived from the CNDS.

      These two frontal-striatal neural circuits - the limbic loop (ventromedial prefrontal cortex
      (vmPFC)-ventral striatum), and executive control loop (dorsolateral PFC (dlPFC)-dorsal
      striatum) can be differentially stimulated by theta burst stimulation (TBS), a patterned form
      of transcranial magnetic stimulation (TMS). Continuous TBS (cTBS) results in long term
      depression (LTD) of cortical excitability and intermittent TBS (iTBS) results in potentiation
      (LTP). Recent studies by our group have demonstrated that LTD-like cTBS to the vmPFC (Aim 1)
      attenuates brain activity in the nucleus accumbens (Hanlon et al. 2015) and salience network
      (2017). In a collaborative MUSC/VTCRI study, 5 days of vmPFC cTBS reduced the value of
      cigarettes, preference for immediate gratification, and smoking cue-evoked brain activity.
      Alternatively, other investigators have demonstrated that LTP-like stimulation to the dlPFC
      (Aim 2) decreases cigarette craving and cigarette use. These studies support the targets
      specified by CNDS. The investigators will evaluate the relative efficacy of these 2
      strategies as novel tools to change smoking-related behaviors and dampen brain reactivity to
      cues in two double-blind, sham- controlled neuroimaging studies. The investigators long-term
      vision is that TBS would be used as an acute intervention enabling individuals to get through
      the first week after a smoking quit attempt without relapsing, and transition to more
      sustainable mechanisms of behavioral change (e.g., medication, cognitive behavioral therapy).

      Aim 1 (Strategy 1): Modulating the limbic system as an approach to treatment: vmPFC TBS.
      Cigarette smokers will be randomized to receive 10 days of real TBS or sham TBS directed to
      the vmPFC. Intermittently the desire to smoke, cigarette value using behavioral economic
      demand, preference for immediate gratification (delay discounting), and cigarette
      self-administration will be assessed. Smoking cue-evoked brain activity will also be measured
      when individuals are asked to 'crave' (passive limbic engagement) versus 'resist' the craving
      (executive engagement). The investigators hypothesize that TBS will: 1) decrease the
      behavioral smoking measures described above, which will be explained by a selective 2)
      decrease in the neural response to cues when individuals 'allow' themselves to crave, and 3)
      sustain these changes over a time period sufficient to overcome the initial quit attempt
      (~7-14 days).

      Aim 2 (Strategy 2): Modulating the executive system as an approach to treatment: dlPFC iTBS.
      Aim 2 will follow the design of Aim 1. The procedures will be identical, except TBS will be
      delivered to the left dlPFC. The investigators hypothesize that TBS will: 1) decrease the
      behavioral smoking measures described above, which will be explained by a selective 2)
      increase in the neural response to cues when individuals attempt to 'resist' the cues, and
      again 3) sustain these changes over a similar period as specified in Aim 1.

      Exploratory Aim: Evaluate baseline frontal striatal connectivity and discounting rate as
      factors to predict an individual's likelihood of responding to Strategy 1 versus Strategy 2.
      The investigators will test the hypotheses that individuals with a higher ratio of
      (vmPFC-striatal)/(dlPFC-striatal) connectivity will be more likely to have a behavioral
      change after Strategy 1. Various demographics (e.g. gender, smoking history, socioeconomic
      status, sub clinical depressive symptoms, self-efficacy, & motivation to quit will be
      evaluated as explanatory variables.

      The outcomes of the present aims will resolve a critical gap in the investigator's knowledge
      regarding the relative efficacy of 2 promising TMS treatment strategies. These outcomes will
      be directly translated to a larger longitudinal study evaluating a multi-pronged approach to
      improving outcomes in traditional pharmacotherapy or behavioral treatments.
    

Intervention name(s): Real TBS to the vmPFC; Sham cTBS to the vmPFC; Real TBS to the dlPFC; Sham TBS to the dlPFC
Intervention type(s): Device; Device; Device; Device
Intervention description(s): This will be delivered with the Magventure Magpro system; active sham coil (double blinded); The MagVenture MagPro system has an integrated active sham that uses two surface electrodes placed on the skin beneath the coil.; This will be delivered with the Magventure Magpro system; active sham coil (double blinded).; The MagVenture MagPro system has an integrated active sham that uses two surface electrodes placed on the skin beneath the coil.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Device Feasibility
Keywords: Transcranial Magnetic Stimulation; Brain Stimulation; Treatment; Neuroimaging