by Jennifer Bolton and Serena Smith, TMS Clinicians at SeattleNTC
Tobacco use is the leading cause of preventable death in developed countries. Despite smokers frequently identifying tobacco use as harmful and expressing a desire to reduce or stop smoking, most smokers have difficulty abstaining. Eighty-five percent of those who attempt to quit smoking without assistance relapse, with the majority resuming use within one week of quitting. Numerous aids have been helpful in increasing immediate abstinence rates, but the long-term outcomes are still disappointing. After 6 months, common aids, such as nicotine gum and bupropion (a prescription medication) result in abstinence rates of only 19% and 24% respectively. 
The addictive properties of tobacco are caused primarily by the action of nicotine on the central nervous system. Initially, nicotine increases the release of dopamine a neurotransmitter or chemical messenger, in the reward centers of the brain. However, prolonged exposure to even low concentrations of nicotine can cause the desensitization of dopamine neurons, making them harder to activate. Decreased activity in the reward-related brain circuits is correlated with higher levels of craving and relapse.
One tool being studied to treat smoking addiction is repetitive transcranial magnetic stimulation (rTMS), a safe and noninvasive method of brain stimulation that uses magnetic pulses to produce changes in brain activity. rTMS can trigger dopamine release and generate lasting changes in neural excitability. It has been hypothesized that by increasing the activity of the neural circuits involved in nicotine addition, rTMS may help people stop smoking cigarettes
There are two basic forms of rTMS, conventional and deep. Conventional rTMS, which stimulates relatively superficial layers of the brain, has been shown to reduce cigarette consumption and cravings, at least temporarily, by a decade of research. Amiaz et al. discovered that rTMS administered daily for 10 days to the left dorsolateral prefrontal cortex (DLPFC), a region of the brain with strong connections to reward circuitry reduced the consumption of cigarettes, dependence on nicotine, and the craving provoked by smoking cues. However, these effects tended to fade quickly.
In contrast, a recent study by Dinur-Klein et al. suggests that targeting deeper targets, such as the insular cortices, may offer improved, long-term outcomes. In an attempt to find a more durable treatment, Dinur-Klein et al. used a deep rTMS H-coil to target both the right and left dorsolateral prefrontal cortices as well as the insulae—deep brain structures that have been implicated in craving by neuroimaging studies.
In Dinur-Klein et al.’s study of deep TMS for smoking cessation, adults were recruited who smoked at least 20 cigarettes a day and had previously failed cessation with other treatments. Participants were randomly placed into 6 experimental groups with variations in rTMS frequency (high frequency, low frequency, sham, or simulated stimulation), and differences in smoking cues (with cues and without cues before each treatment). Each group received a total of 13 daily TMS treatment sessions and had cigarette consumption monitored by self-reports and analysis of urine samples for levels of cotinine, a metabolite that appears in urine after nicotine has been consumed.
In the low frequency rTMS and the sham groups only 9% of participants abstained from smoking at the end of the 13 treatments and none remained abstinent 6 months later. However, the groups receiving high frequency rTMS showed a significant reduction in cigarette consumption and nicotine dependence. Specifically, the group receiving high frequency rTMS after being shown a smoking cue exhibited the greatest response with a 44% abstinence rate at the end of the 13 treatments and a 33% abstinence rate at a 6 month follow up. Thus, being shown a smoking cue followed by high frequency rTMS more than quadrupled the likelihood of abstinence after the 13 treatments and helped subjects maintain long-term abstinence.
In conclusion, deep TMS has promise as a safe, effective, and durable treatment for cigarette addiction. However, these findings are very preliminary, and additional research is necessary prior to the routine clinical application of rTMS for this indication.
 World Health Organization (2013): WHO report on the global tobacco epidemic. Geneva: World Health Organization
 Agency for Healthcare Research and Quality (2008): National Guideline C Treating tobacco use and dependence: 2008 update. Rockville MD: AHRQ. Page 109.
 Pidoplichko V, DeBiasi M, Williams J, Dani J (1997): Nicotine activates and desensitizes midbrain dopamine neurons. Nature V 390: 401-404.
 Amiaz R, Levy D, Vainiger D, Grunhaus L, Zangen A (2009): Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. Addiction 104:653-660.
 Dinur-Klein L, Dannon P, Hadar A, Rosenberg O, Roth Y, Kotler M, Zangen A (2014): Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: A prospective, randomized controlled trial. Biol Psychiatry 76:742-49.