Deep Repetitive Transcranial Magnetic Stimulation for Smoking Cessation: Is Going Deeper Better?

Abstract

In this issue of Biological Psychiatry, Dinur-Klein et al. (1) report on an impressive proof-of-concept study using a randomized, double-blind, sham-controlled trial design that demonstrates 10-Hz deep repetitive transcranial magnetic stimulation (TMS) using H-coil methods administered bilaterally to the dorsolateral prefrontal cortex (DLPFC) and insular cortex could reduce shortterm biochemically verified cigarette consumption and nicotine dependence levels and increase short-term and long-term smoking abstinence rates. The lack of observed effects on craving are not surprising in a clinical trial setting because subjects were at various stages of cigarette use (no change, reduced, abstinent), which would have produced significant intersubject variability in this measure. The effects of 10-Hz repetitive TMS on certain outcomes (e.g., nicotine dependence) may have been enhanced through cigarette cue exposure before the stimulation; however, these effects were underpowered. Nonetheless, this study is a fine example of a neuroscience-informed, hypothesis-driven addiction treatment trial that is certain to set the standard for future work in the field of brain stimulation methods for the treatment of tobacco dependence. A decade of research has suggested that superficial brain stimulation may transiently reduce cravings and consumption in tobacco-dependent individuals (2). In their timely study, DinurKlein et al. extended previous work and conducted the first smoking cessation trial employing the H-coil, which has been shown to target brain regions approximately 5–7 cm deep. This focal depth with the H-coil is very exciting given its potential to target the brain reward circuitry that mediates all drugs of addiction. However, is going deeper better for tobacco treatment outcomes? The findings from the study by Dinur-Klein et al. suggest that targeting the insular cortex rather than superficial brain regions such as the DLPFC may be the key to successful smoking cessation and possibly better long-term outcomes. It is unclear if cue exposure reduces nicotine dependence, reduces level of cravings, or improves abstinence rates. Borrowing from the posttraumatic stress disorder research conducted by the same group, this study evaluated if cue exposure—in this case, observing someone else lighting the subject’s preferred brand of cigarette—would enhance the effects of repetitive TMS. The authors suggested that cue exposure before repetitive TMS activates the neurocircuitry that mediates cue-induced craving and that repetitive TMS would subsequently disrupt drug-related memory consolidation. Although this study was underpowered to evaluate the effects of cue exposure on the outcome measures, it