Working Memory Training Combined With Transcranial Magnetic Stimulation in Smokers
Condition: Tobacco Use Disorder
MeSH terms: Tobacco Use Disorder
Intervention: Working Memory Training; Sham Working Memory Training; repetitive Transcranial Magnetic Stimulation; Sham repetitive Transcranial Magnetic Stimulation
Intervention description: The Working Memory Training condition: This condition will include 30 sessions across 4 weeks (10 remote sessions prior to initiation of the rTMS stimulation, and 20 lab sessions on rTMS stimulation days). Participants will complete three distinct WM tasks in each session: a visuospatial WM task, a backward digit span task, and a letter span task. In the training condition, the difficulty level of all three WM tasks will be automatically adjusted on a trial-by-trial basis. An identical protocol and software have demonstrated efficacy in increasing WM capacity, and this improvement in WM predicts reduction in addictive behavior.; In the Sham WMT condition, the difficulty level of the WM tasks will not be adjusted; instead it will remain at the initial easy level throughout each task (i.e., three items in each sequence). All other aspects of the condition are identical to the active WMT condition.; The rTMS Condition: rTMS will be delivered with a Magstim Rapid2 system using Magstim Air Film Coils. rTMS pulses will be delivered at 10 Hz (100% resting motor threshold, RMT) in 40, 5 second trains, with 15 second inter-train interval, for a total of 2000 pulses per session. Active or sham rTMS will be applied over the left DLPFC; corresponding with the standard "F3" location on scalp (F3=left frontal lobe, location #3 for electrode placement using international 10-20 system for scalp measurements). Five consecutive daily sessions will occur on two consecutive weeks, for a total of 10 sessions. RMT, defined as the amount of energy required to induce movement in the contralateral abducer pollicis brevis in at least 50% of stimulations, will be assessed on first day of application.; Sham rTMS will be identical to active treatment, with the exception that mu-metal plates attached to the sham coil block the magnetic field while providing a sensation of stimulation.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: A 2x2 factorial model will include four groups (Working Memory Training [WMT] + repetitive Transcranial Magnetic Stimulation ]rTMS], sham WMT+rTMS, WMT+sham TMS, and sham WMT+sham rTMS) capable of isolating independent and combined effects of WMT and rTMS on the primary outcome variables.
Masking: Double (Participant, Care Provider)
Masking description: The participant will be prevented from having knowledge of the interventions assigned.
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Smoking remains the leading cause of preventable death in the United States, and current
      first-line treatments leave the majority of tobacco dependent individuals unable to quit. The
      inability to quit despite motivation to do so, is thought to result in part, from
      self-control failure. Working memory (WM) deficits contribute to imbalanced self-control and
      allow automatic impulses to drive behavior. Thus, WM plays a critical role in addictive
      behavior, and is particularly relevant to smoking. Indeed, a strong link between WM and
      smoking has been established in the literature; most notably, degree of WM impairment and
      deficits in activation in associated brain regions predict time to relapse, and WM moderates
      the relationship between craving and relapse. Given these insights, researchers have been
      examining interventions that may target WM including WM training (WMT) and repetitive
      Transcranial Magnetic Stimulation (rTMS). WMT involves taxing this executive function
      repeatedly over time and has shown positive preliminary results in improving measures of
      self-control and reducing consumption of addictive substances. Similarly, rTMS, a
      non-invasive brain stimulation procedure that stimulates neuronal tissues and increases
      cortical excitability, has been shown to increase WM capacity and reduce craving and
      consumption of several addictive substances including nicotine. While these interventions
      have demonstrated initial promise in affecting addictive behaviors, the magnitude and
      durability of their effects may be limited. Recently, researchers have posited - but not yet
      empirically tested - that WMT administered in combination with rTMS may result in an additive
      or supra-additive effect in treating addictive processes. This is highly significant; the
      clinical utility of rTMS over current first line treatments may be limited if factors with
      potential to enhance its effectiveness are not examined. Given these recent advances in the
      literature, the primary objective of the proposed study is to evaluate the individual and
      combined effects of Working Memory (WM) training and repetitive Transcranial Magnetic
      Stimulation (rTMS) on WM performance and smoking behaviors as well as critical mediators of
      these effects. These aims will be examined in a sample of tobacco dependent adults (N=130)
      utilizing a 2x2 factorial experimental design including four groups (WMT+rTMS, sham WMT+rTMS,
      WMT+sham TMS, and sham WMT+sham rTMS) capable of isolating independent and combined effects
      of WMT and rTMS.
    

Eligibility criteria:

        Inclusion Criteria:

          -  meet safety guidelines for application of rTMS

          -  be 18-60 years of age

          -  have smoked cigarettes regularly for at least one year

          -  currently smoke at least 10 cigarettes per day

          -  have a carbon monoxide (CO) level >10 ppm

          -  currently use no other nicotine products regularly

        Exclusion Criteria:

          -  meet criteria for current alcohol or substance dependence

          -  have a current affective disorder (depression, dysthymia, or mania) or psychotic
             symptoms

          -  are currently pregnant or lactating, or intend to become pregnant

          -  have a health condition for which rTMS is contraindicated