At a glance
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Working Memory Training Combined With Transcranial Magnetic Stimulation in Smokers: 2x2 Factorial Study
In Brief
A Phase 2 clinical trial evaluating Working Memory Training, Sham Working Memory Training, and 2 other interventions for Tobacco Use Disorder. Completed, enrolled 50 participants across 2 sites.
Detailed 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.
Study Details
Timeline
Interventions
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.