Journal of Psychiatric Research 54 (2014) 19e25

Contents lists available at ScienceDirect

Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/psychires

Transcranial direct current stimulation of the frontal-parietaltemporal area attenuates smoking behavior Zhiqiang Meng a, b, *, Chang Liu a, b, Chengyang Yu a, Yuanye Ma a, b, c, ** a State Key Laboratory of Brain and Cognitive Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, 32# Jiao Chang Dong Lu, Kunming, Yunnan 650223, China b State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China c Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, China

a r t i c l e i n f o

a b s t r a c t

Article history: Received 16 October 2013 Received in revised form 11 March 2014 Accepted 11 March 2014

Many brain regions are involved in smoking addiction (e.g. insula, ventral tegmental area, prefrontal cortex and hippocampus), and the manipulation of the activity of these brain regions can show a modification of smoking behavior. Low current transcranial direct current stimulation (tDCS) is a noninvasive way to manipulate cortical excitability, and thus brain function and associated behaviors. In this study, we examined the effects of inhibiting the frontal-parietal-temporal association area (FPT) on attention bias to smoking-related cues and smoking behavior in tobacco users. This inhibition is induced by cathodal tDCS stimulation. We tested three stimulation conditions: 1) bilateral cathodal over both sides of FPT; 2) cathodal over right FPT; and 3) sham-tDCS. Visual attention bias to smoking-related cues was evaluated using an eye tracking system. The measurement for smoking behavior was the number of daily cigarettes consumed before and after tDCS treatment. We found that, after bilateral cathodal stimulation of the FPT area, while the attention to smoking-related cues showed a decreased trend, the effects were not significantly different from sham stimulation. The daily cigarette consumption was reduced to a significant level. These effects were not seen under single cathodal tDCS or sham-tDCS. Our results show that low current tDCS of FPT area attenuates smoking cue-related attention and smoking behavior. This non-invasive brain stimulation technique, targeted at FPT areas, might be a promising method for treating smoking behavior. Ó 2014 Elsevier Ltd. All rights reserved.

Keywords: Smoking behavior Frontal-parietal-temporal area Smoking cue-related attention Tobacco addiction Transcranial direct current stimulation (tDCS)

1. Objectives of the study and background Tobacco smoking is an addictive behavior, and it is the single greatest common preventable cause of morbidity and mortality (Peto et al., 1992). Yet despite years of research into the brain mechanisms and treatments, smoking remains one of the most serious threats to public health all over the world (Singer et al., 2011). Tobacco addiction is characterized by the loss of control over cigarette smoking and the compulsive smoking behavior regardless of negative consequences. Currently available treatments for smoking addiction remain inadequate for most smokers. Smoking-related cues remain as a major cause for relapse in former smokers, usually leading to the re-establishment of their habit * Corresponding author. Tel.: þ1 508 624 8089. ** Corresponding author. Kunming Institute of Zoology, Chinese Academy of Sciences, 32# Jiao Chang Dong Lu, Kunming, Yunnan 650223, China. Tel.: þ86 871 65193083; fax: þ86 871 65191823. E-mail addresses: [email protected], [email protected] (Z. Meng), [email protected] (Y. Ma). http://dx.doi.org/10.1016/j.jpsychires.2014.03.007 0022-3956/Ó 2014 Elsevier Ltd. All rights reserved.

within one year of quitting (Fant et al., 2009; Piasecki, 2006). Consequently, there is intense interest in better understanding the neurobiology of smoking addiction and developing more effective treatments. Smoking addiction is a brain disorder and chronic smoking induces long-term adaptations in multiple neural systems and brain regions. Functional imaging studies have shown that many cortical regions are involved in smoking addiction, such as the mesocorticolimbic reward areas (e.g., ventral tegmental area), hippocampus (memory), prefrontal cortex (visuospatial attention), and the insula (interoception) (Due et al., 2002; Garavan et al., 2000; Goldstein and Volkow, 2002). Activity within the insula has been shown to correlate with subjective cue-induced drug urges (Bonson et al., 2002; Brody et al., 2002). Smokers with damage to the insula quitted smoking more easily, without persistence of the urge to smoke (Naqvi et al., 2007). Smokers who suffered a stroke, causing a lesion at the insular cortex, had an improved successful quitting rate relative to those for whom stroke did not result in such a lesion (Suñer-Soler et al., 2012). Additionally, inactivation of the insular

20

Z. Meng et al. / Journal of Psychiatric Research 54 (2014) 19e25

cortex in rats prevented the urge to seek drugs. Similarly, these results were also found when the hippocampus was inactivated (Contreras et al., 2007). Contextual memory is formed and consolidated in the hippocampus. Smoking context-related memory plays a critical role in cue-induced relapse. In addition to the insula and hippocampus, lateral prefrontal cortex and lateral parietal cortex were also shown to be involved in smoking addiction (Due et al., 2002). Functional magnetic resonance imaging studies showed that visual smokingrelated images could elicit a greater activation of these areas in smokers than neutral images. These studies suggest that the insula, hippocampus, and prefrontal cortex are critical brain regions involved in smoking addiction. Thus, modulation of the activity of these brain areas may have therapeutic effects beneficial to cessation of smoking behavior. Transcranial direct current stimulation (tDCS) is a non-invasive method for modulating cortical excitability that has undergone resurgence in recent years (Nitsche and Paulus, 2011). The cerebral cortex is stimulated through a weak constant electric current which can induce changes in cortical excitability that lasts beyond the stimulation period (Nitsche et al., 2004; Nitsche and Paulus, 2001; Nitsche et al., 2005). The current flows from the anode to the cathode, some being diverted through the scalp and some moving through the brain, and leads to increases or decreases in cortical excitability dependent on the direction and intensity of the current (Miranda et al., 2006). Anodal tDCS typically has an excitatory effect on the local cerebral cortex by depolarizing neurons, while the converse applies under the cathode through a process of hyperpolarization (Nitsche et al., 2003). As tDCS offers the possibility of manipulating cortical excitability in a non-invasive way, raising the opportunity for numerous studies to be conducted in both basic brain research and the field of restorative neurology (Nitsche & Paulus, 2011). For instance, tDCS has been shown to improve the cognitive performance in Alzheimer Disease (Nardone et al., 2012) and motor function in Parkinson’s disease (Fregni et al., 2006). Studies have also shown that tDCS stimulation has acute therapeutic effects on inhibitory executive control of voluntary actions (Hsu et al., 2011), alcoholism (Boggio et al., 2008) and many other kinds of brain functions (pain, depression, risk-taking behaviors et al., Nitsche & Paulus, 2011). In the present study, we inhibited the frontal-parietal-temporal association area (FPT) by tDCS to examine whether changing the excitability of these brain areas could affect smoking behavior. Smokers exhibit attentional bias toward smoking-related stimuli which is thought to be one of the main factors that induce relapse (Chanon et al., 2010). Thus, we also tested whether tDCS can change the attention to smoking-related stimuli. We found that bilateral cathodal stimulation of FPT cortices could decrease attention to smoking-cues and attenuate smoking behavior measured as daily cigarette consumption. Our results indicate that the activity of these cortices is associated with smoking behavior, and inhibiting these areas by tDCS might provide a new therapeutic method for treating tobacco addiction. 2. Materials and methods 2.1. Participant recruitment and screening Participants were recruited by local advertisements in newspapers and notices distributed throughout local colleges and communities in the greater Kunming area. The participants were prescreened using the following criteria: 1) 18e55 years old; 2) no history of major neurological disorders (e.g., seizure, dementia, Parkinson’s disease, depression); 3) no brain injury or stroke history; 4) at least two years of smoking history with more than 8

cigarettes daily; 5) no vision diseases; 6) no smoking cessation therapy history; 7) currently not on medication with active central nervous system properties; 8) no chronic pain or hyperalgesia. Thirty male Chinese participants were recruited for the present study. The average age was 23.7  7.2; average years of smoking were 6.6  6.7 and daily cigarette number was 15.8  6.4. All data were shown as mean  SD. All experiments were approved by the Ethics Committee of Kunming Institute of Zoology, Kunming, and conform to the principles of the Declaration of Helsinki (BMJ 1991; 302: 1194). All subjects gave their written informed consent for the study indicating that they received a detailed description of the experimental procedures and the potential risk of the tDCS treatment. Subjects were reimbursed for their time and they could choose to withdraw from the study at any time if it was uncomfortable for them. 2.2. Direct current stimulation Low direct current was delivered by a custom made battery-driven constant current stimulator, and transferred through the scalp via saline-soaked surface sponge electrodes (diameter ¼ 6.5 cm). The output current was adjustable, from 0.1 mA to 5 mA. The electrodes were placed on to the areas between T3, F3, C3 and F7 (Fig. 1) according to the 10e20 international system for electroencephalography (EEG) electrode placement (Klem et al., 1999). The method of using EEG electrode positions for brain areas localization has been used widely in both tDCS studies and transcranial magnetic stimulation (TMS) studies (Nitsche & Paulus, 2011). The electrode polarities were set depending on the experiments design. During the experiments, the participants were seated comfortably in a low illuminated, quiet room. During stimulation, a constant current of 1 mA was applied to the subjects for 20 min. Subjects could feel the current around the electrodes at the beginning of the stimulation. For sham stimulation, the same electrodes positions were used as in the tDCS stimulation condition, but the current was ramped down after 30 s without the subject’s knowledge (Zaehle et al., 2011). Therefore, the subjects felt the initial itching sensation at the beginning of the procedure, but received no current for the rest of the stimulation period. This procedure allowed us to blind subjects for the respective stimulation condition as all participants experienced the initial itching and thought they received tDCS treatment. 2.3. Eye tracking system and visual stimuli Tobii eye tracking system (Tobii Technology AB, Sweden) was used to investigate the effects of tDCS on attention to smokingrelated cues. A 17 inch LCD screen was placed 70 cm in front of subjects. The center of the screen was at the height of the subject’s eyes. A visual attention procedure was used to test the participant’s attention function. The tests started with the appearance of a fixation dot in the center of the screen. After 2 s, a four-quadrant picture was presented on the screen (see Fig. 2A for a sample stimulus). Each picture consisted of 4 different objects with one in each quadrant. One of the objects was smoking or cigarette related cue (e.g. a burning cigarette), the others were neutral stimuli (e.g. a cup). The location of the smoking cue in the four quadrants was randomized and counterbalanced. The presentation time of the visual stimuli was 5 s with a 5e10 s time out. During the presentation of visual stimuli, participants could explore the screen freely. Tobii Studio 1.7 (with the eye tracking system) was used to track the participant’s eye position and movement during visual stimuli presentation. The fixation counts in each quarter were recorded by the eye tracking system for offline analysis.

Z. Meng et al. / Journal of Psychiatric Research 54 (2014) 19e25

21

Fig. 1. Schematic diagram of the electrodes locations and relative cortical areas. Custom made electrodes were placed on the participants’ scalp according to the electroencephalography map. A) Lateral view of the locations of electrodes on the scalp. B) Top view of the locations of electrodes on the scalp.

2.4. Experiment design Although both sides of the cortices are involved in smoking addiction (Goldstein and Volkow, 2002; Naqvi et al., 2007), studies have suggested that the right hemisphere might have greater importance in smoking relapse than the left side (Naqvi et al., 2007; Paulus et al., 2005). To test whether inhibiting right FPT alone was enough to induce behavioral effects, in this present study, we designed two different tDCS stimulation conditions: 1) the cathodal electrode was placed at the right FPT area and the anodal electrode was placed on the left FPT area (referred to as single cathodal stimulation); 2) two cathodal electrodes were placed on each side of FPT area, while two anodal electrodes were placed at the occipital lobe on respective side (referred to as double cathodal stimulation). For the sham stimulation group, the electrodes positions were the same as in the double cathodal condition, but underwent sham stimulation (see above description). All participants were first randomly assigned to one of the three groups (n ¼ 10 each group at the beginning of experiments). Later, the socio-demographic for each group was balanced by years of smoking and daily cigarette number. The average age in sham, unilateral stimulation and bilateral stimulation group was 22.1  4.4, 26.7  8.4 and 23.8  4.1, respectively. The average years of smoking in sham, unilateral stimulation and bilateral stimulation group was 4.4  3.0, 3.3  1.7 and 8.5  8.1, respectively. The average daily cigarette number in sham, unilateral stimulation and bilateral stimulation group was 12.9  5.4, 17.7  6.1 and 15.7  7.7, respectively. All data are shown as mean  SD. ANOVA showed no significant difference for any factor. Data collection was blind to the tDCS procedure. 2.5. Experiment protocol Before the experiments, the participants were allowed to stay in the test room for 5 min to become familiar with the environment. The experiment consisted of three sessions: pre-stimulation session, stimulation session, and post-stimulation session. In the prestimulation session, twenty different visual stimuli were shown in a random order. The pre-stimulation session was followed immediately by the stimulation session, where the participants received either double cathodal, single cathodal, or sham stimulation for 20 min. To reduce the stress or discomfort of being treated in this low-light laboratory environment, television and books were available to the participants. After 20 min, two tests were

performed in the post stimulation session. First, the visual attention to the smoking-related objects was tested using the same procedure as in the pre-stimulation session, but using a different group of visual stimuli. The eye positions and movements were recorded and analyzed by the eye tracking system. Second, a questionnaire regarding the sensation of the tDCS was completed. Lastly, 24 h after the stimulation, the participants reported the numbers of cigarette smoked since stimulation and any uncomfortable sensation. 2.6. Data analysis The number of daily cigarettes smoked was used to evaluate the smoking behavior. (Post stimulationePre stimulation)/Pre stimulation fixation counts in smoking-related cues area and daily cigarette number was used to evaluate the effects of tDCS on smoking behavior. Pre-tDCS daily cigarette number was the average daily cigarette number in the previous week. In the attention task, total exploring time ¼ average fixation time*fixation counts þ saccade time. Total exploring time and fixation counts were positively correlated, and fixation counts contained information about the exploring pattern. Thus fixation counts in each quarter of the visual stimuli were used in this study to evaluate the attention bias on smoking-related pictures. For the pictures that were presented multiple times, only the fixation counts of the first presentation were used for data analysis. The data was discarded if the total fixation count was 0. One participant from the single stimulation group was excluded because we lost contact with him after the experiment, so we could not collect the data for after-treatment. One participant from the double stimulation group was excluded because he was found to have been enrolled in a cessation therapy in the last year, which failed to meet our enrollment criteria. One participant from the sham group was excluded because he was sick the day after the experiment and took medications (use of medication failed to meet our enrollment criteria). Two-way repeated measures with tDCS type (sham, single cathodal and double cathodal) and treatment time (pre-tDCS vs. post-tDCS) as factors was used for statistical analysis. Age, smoking history and daily cigarette consumption number were treated as covariates. Unilateral group and bilateral group were compared to sham group separately because of the small sample size. Post-hoc HolmeSidak t-test or Wilcoxon Signed rank test was used to determine the difference within groups (pre-

22

Z. Meng et al. / Journal of Psychiatric Research 54 (2014) 19e25

tDCS vs. post-tDCS). ManneWhitney Rank Sum test was used to examine the differences between attention to smoking cues and non-smoking cues in the pre-stimulation session. Percentage changes after tDCS stimulation ((post-pre)/pre*100%) was used to examine the correlation coefficient between changes in visual attention and cigarette consumption. A criterion of statistical significance of 0.05 was used in all the tests. Two-way repeated measures of covariates were done using SPSS 21.0. All other analyses were done with SigmaPlot 12.0 (Systat Software, Inc. USA). In addition to the daily cigarette number, we recorded the selfreported sensory ratings at the beginning period of the stimulation. We also investigated if there was any uncomfortable or abnormal feeling 24 h after stimulation by using questionnaires. These data were used to evaluate the intensity and any side effects of the stimulation. However, inasmuch as these evaluations were exploratory in nature, no statistical comparison was made. 3. Results 3.1. Effects of tDCS on attention to smoking cues Attention bias to smoking-related cues was examined before the tDCS treatment. The fixation counts in the smoking cue area were significantly greater than the average fixation counts in each nonsmoking cue area in all the three treatment groups (ManneWhitney Rank Sum Test, p < 0.05 for all three groups; Fig. 2B). There were no significant group differences for the fixation counts in smoking cue areas before tDCS (One way ANOVA, F (2, 132) ¼ 2.75, p > 0.05). The effects of tDCS on smoking cue-related attention were examined after tDCS. Two-way repeated measures ANCOVA showed no significant interaction effects between tDCS types and treatment time when compared sham vs. single cathodal group (F (1, 13) ¼ 0.20, p ¼ 0.66, h2p ¼ 0.02). Their interaction effects between treatment time and age, smoking history, or daily cigarette number were all not significant (all Fs < 1.4, all ps > 0.2). When we compared the sham vs. the double cathodal group, two-way repeated measures ANCOVA showed no significant interaction effects between tDCS types and treatment time (F (1, 13) ¼ 4.05, p ¼ 0.06, h2p ¼ 0.24). All other main effects and interactions were also not significant (all Fs < 3.2, all ps  0.1). Post-hoc tests showed that double cathodal stimulation reduced smoking cue-related attention as indicated by significantly fewer fixation counts in smoking cue areas (Wilcoxon Signed Rank Test, p < 0.05, Fig. 2C). To test whether the attentional changes applied to only the smoking cues or all visual cues, the effects of tDCS on attention to the non-smoking cue areas after treatment were also evaluated. Two-way repeated measures were used for the analysis. Age, smoking history and daily cigarette number were treated as covariates. All the main effects and interaction effects were not significant (all Fs < 1.2, all ps > 0.3). 3.2. Effects of tDCS on daily cigarette consumption

Fig. 2. Effects of transcranial direct current stimulation (tDCS) on smoking cue-related visual attention. A. A sample visual stimulus with the eye movement tracks. Each blue dot is a visual exploration point. The numbers indicate the sequence of eye movement and the size of the dot indicates the fixation time. B. Attentional bias to smoking related cues before tDCS. Data were shown as the fixation counts in smoking cue area and non-smoking cue areas (Median  Quartiles; SC, smoking cue; NSC, non-smoking cue). C. Effects of tDCS on attentional bias to smoking related cues. Data were shown as the fixation counts in smoking cue area before and after tDCS (Median  Quartiles). N ¼ 9 each group; Sham, sham stimulation group; SS, single cathodal stimulation group; DS, double cathodal stimulation group; *, p < 0.05, Wilcoxon Signed Rank Test. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

When we compared double cathadol stimulation to sham control group, two-way repeated measures ANOVA showed significant interaction effects between tDCS types and treatment time (F (1, 13) ¼ 10.4, p ¼ 0.007, h2p ¼ 0.44). Significant interaction effects were also found between treatment time and daily cigarette consumption number (F (1, 13) ¼ 13.37, p ¼ 0.003, h2p ¼ 0.5). All other main effects and interactions were not significant (all Fs < 0.52, all ps > 0.5, Fig. 3A). Post-hoc HolmeSidak test showed that double cathodal direct current stimulation significantly reduced the daily cigarette consumption (t ¼ 5.1, p < 0.05, Fig. 3B). When we compared single cathadol stimulation to the sham group, no significant treatment time  tDCS type interaction effect was found (F

Z. Meng et al. / Journal of Psychiatric Research 54 (2014) 19e25

23

the three stimulating conditions. After 24 h of the stimulation, no obvious aversive effects or any uncomfortable feelings were reported by any participant. 4. Discussion

Fig. 3. Effects of transcranial direct current stimulation (tDCS) on daily cigarette smoking number. Panel A. The daily cigarette numbers of three treatment groups both before and after tDCS. Panel B. The effects of tDCS on daily cigarette number changes. The data in panel B is presented as the percentage changes. Sham, sham stimulation group; SS, single cathodal stimulation group; DS, double cathodal stimulation group; N ¼ 9 each group; *, p < 0.05, Paired t test.

(1, 13) ¼ 0.34, p ¼ 0.57, h2p ¼ 0.026). However, significant interaction between treatment time and daily cigarette number was detected (F (1, 13) ¼ 6.47, p < 0.05, h2p ¼ 0.33). All other main effects and interactions were not significant (all Fs < 0.76, all ps > 0.39). The correlation coefficiency between changes in visual attention and cigarette consumption in each group was evaluated by Pearson Product Moment Correlation. The Pearson’s r was 0.24, 0.27 and 0.657 for sham, single cathodal and double cathodal stimulation group (n ¼ 9, p ¼ 0.53, 0.48 and 0.056 respectively). The self-reported sensations of stimulation in each condition are shown in Table 1. The most commonly reported sensation was tingling and itching. No severe sensory effects were found in any of Table 1 The initial sensations of each stimulation condition (numbers of reports). Stimulation condition

No sensation

Itching

Tingling

Mild pain

Dizziness

Severe pain

Sham Single cathodal Double cathodal

3 2

3 5

5 4

3 1

0 1

0 0

0

3

7

4

1

0

In the present study, we assessed the effects of tDCS application over the frontal-parietal-temporal (FPT) area on tobacco smoking behavior. Bilateral cathodal stimulation of the FPT areas significantly reduced the attention to smoking-related cues and daily cigarette consumption on the following day. Anodal stimulation on left FPT and cathodal stimulation on the right FPT failed to reduce smoking behavior or attention towards smoking cues. No effects were found in the sham-tDCS group. TDCS of the FPT area may affect many brain areas, such as the insula, hippocampus, lateral prefrontal cortex, and other brain areas, to reduce smoking behavior. These results are consistent with the generally known functions of these brain regions. First, the insula is the interoceptive states representation area and activity in the insula has been shown to correlate with subjection cue-induced urge to use drugs. Damage to the insular cortices has been shown to disrupt the addiction to cigarette smoking (Naqvi et al., 2007). Secondly, the hippocampus is very important for associative memory including smoking-related memory. Contextual cues associated with smoking can elicit cravings in smokers (Gallinat et al., 2007; Davis and Gould, 2008). Cathodal tDCS stimulation might inhibit the activity of hippocampus, and therefore suppress smoking-related memory. This memory suppression might then facilitate a reduction in the urge to smoke (Hyman, 2005). Thirdly, the dorsolateral prefrontal cortex has been proposed to associate with higher cognitive functions such as working memory and visuospatial attention (McCarthy et al., 1997). Thus, the cathodal stimulation in the present study might reduce the smoking cuerelated attention by inhibiting the activity of these brain areas. In addition, a previous study showed that tDCS stimulation of a single side of the dorsolateral prefrontal cortex reduced cue-provoked smoking craving (Fregni et al., 2008). In this study, we cannot confirm that these brain areas were stimulated precisely as described or that no other brain regions were affected. It is very difficult to model the current distribution or measure the activity of the brain under stimulation, thus the exact areas affected in the current study were not identified. As the direct effects of tDCS are limited to surface regions of the cortex, any effects on deeper structures such as hippocampus and insula may be due to a disruption of the connectivity networks. On the other hand, it is possible that nearby brain regions were also stimulated. Smoking-related cues can elicit the urge to smoke (Droungas et al., 1995) and is one of the most important factors that contribute to relapse (Fagerström, 2002). Although we didn’t test the causal role of the smoking cue-related attention, it is possible that the participants smoked fewer cigarettes after stimulation due to them giving less attention to smoking related cues. Previous studies have shown that an attentional bias to smoking-related cues may predict the outcome in smoking cessation (Waters et al., 2003). Our results also showed that there was a positive correlation between changes in visual attention and cigarette consumption in double cathodal stimulation group. Therefore, it is possible that the urge to smoke was reduced by tDCS. Because many antismoking public service advertisements contain smoking cues, reducing smokers’ attention to these smoking-related cues might be an effective approach to prevent the urge to smoke (Sanders-Jackson et al., 2011). TDCS is a safe, well-tolerated technique with no risk for serious adverse effects. As shown in Table 1, the sensory effects were mild and common, as previously reported (Kessler et al., 2011). This is a

24

Z. Meng et al. / Journal of Psychiatric Research 54 (2014) 19e25

method for non-invasively modulating cortical excitability and activity, which has recently received increased interest regarding its possible clinical applications (Nitsche & Paulus, 2011). Neuronal activity induced by tDCS depends on the polarity of the electrodes. Anode stimulation facilitates cortical excitability, whereas the cathode stimulation inhibits excitability (Lang et al., 2004; Lang et al., 2005). These changes of excitability persist beyond the time of stimulation and can last for hours (Nitsche et al., 2003). This makes it possible to use tDCS as a therapeutic approach to treat various brain disorders (Nitsche & Paulus, 2011). One of the disadvantages of this technique is its low focality. The electric current may reach only the most superficial cortical layer. Deep brain stimulation (DBS) is an alternative technique, however it involves invasive surgery to implant an electrode within the brain, severely reducing the likelihood of voluntary participation. TMS has also been shown to have effects on a wide range of brain and cognitive functions. Studies have found that high frequency repetitive TMS could decrease cigarette and cocaine addiction (Eichhammer et al., 2003; Camprodon et al., 2007). However, it is much more expensive than tDCS, and requires more technical training for clinical treatments. The present study has several limitations. The effect of tDCS on female smokers was not investigated in the present study. Less than 1% of the smokers in China are female and most of them do not like to be known as smokers because of social stigmas (Pathania, 2011). Thus, further studies should confirm the effects of tDCS in female smokers. Also, one of the primary measures we used in the present study was the daily cigarette consumption numbers, which were reported by the participants. A limitation of self-reported questionnaires is inaccuracy. For instance, sometimes the participants could not remember how many cigarettes they had smoked during the past 24 h. Although previous studies also used estimated daily cigarette consumption to evaluate the smoking behavior (Field et al., 2006; Bradley et al., 2003), future studies should also consider other quantitative measures to assess the smoking behavior. Lastly, our results showed the acute effects of just one application of tDCS. Multiple applications may have better therapeutic effects. These results suggest that the FPT area plays important roles in smoking behavior and attention to smoking cues. The FPT area may be a potential target for smoking addiction treatment. Low current tDCS over bilateral FPT could decrease smoking behavior and attention to smoking-related cues. Although other methods (e.g., TMS, deep brain stimulation and pharmacological treatment) are available to treat smoking addiction (Been et al., 2007; Rose et al., 2011), this study might have important clinical implications for smoking addiction treatment using a novel noninvasive technique. Contributors Author ZM and YM designed the experiments. Author ZM, CY and CL performed all the experiments. Author CY and CL recruited participants. Author ZM analyzed the cigarette data; Author CY analyzed the visual attention data. Author ZM and CL wrote the paper. All authors critically reviewed content and approved final version for publication. Funding resources This study was supported by the following grants: National Natural Science Foundation of China (NSFC 31271168, 91132307/ H09, 31070965, Finish-Chinese joint project 813111172); National 973 Project of China (2012CB25500, 2011CB707800).

Conflict of interest The authors have no conflict of interest to declare. Acknowledgments We thank Dr. Jia Lu, Dr. Nanhui Chen and Miss Bo Li for their technical help. We thank Dr. Nathan C. Donelson and Dr. Martha Reed for their comments on the manuscript. References Been G, Ngo TT, Miller SM, Fitzgerald PB. The use of tDCS and CVS as methods of non-invasive brain stimulation. Brain Res Rev 2007;56:346e61. Boggio PS, Sultani N, Fecteau S, Merabet L, Mecca T, Pascual-Leone A, et al. Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study. Drug Alcohol Depend 2008;92:55e60. Bonson KR, Grant SJ, Contoreggi CS, Links JM, Metcalfe J, Weyl HL, et al. Neural systems and cue-induced cocaine craving. Neuropsychopharmacology 2002;26: 376e86. Bradley BP, Mogg K, Wright T, Field M. Neural attentional bias in drug dependence: vigilance for cigarette-related cues in smokers. Psychol Addict Behav 2003;17(1):66e72. Brody AL, Mandelkern MA, London ED, Childress AR, Lee GS, Bota RG, et al. Brain metabolic changes during cigarette craving. Arch Gen Psychiatry 2002;59:1162e72. Camprodon JA, Martinez-Raga J, Alonso-Alonso M, Shih MC, Pascual-Leone A. One session of high frequency repetitive transcranial magnetic stimulation (rTMS) to the right prefrontal cortex transiently reduces cocaine craving. Drug Alcohol Depend 2007;86(1):91e4. Chanon VW, Sours CR, Boettiger CA. Attentional bias toward cigarette cues in active smokers. Psychopharmacology (Berl) 2010;212:309e20. Contreras M, Ceric F, Torrealba F. Inactivation of the interoceptive insula disrupts drug craving and malaise induced by lithium. Science 2007;318:655e8. Davis JA, Gould TJ. Associative learning, the hippocampus, and nicotine addiction. Curr Drug Abuse Rev 2008;1:9e19. Droungas A, Ehrman RN, Childress AR, O’Brien CP. Effect of smoking cues and cigarette availability on craving and smoking behavior. Addict Behav 1995;20: 657e73. Due DL, Huettel SA, Hall WG, Rubin DC. Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: evidence from functional magnetic resonance imaging. Am J Psychiatry 2002;159:954e60. Eichhammer P, Johann M, Kharraz A, Binder H, Pittrow D, Wodarz N, et al. Highfrequency repetitive transcranial magnetic stimulation decreases cigarette smoking. J Clin Psychiatry 2003;64(8):951e3. Fagerström K. The epidemiology of smoking: health consequences and benefits of cessation. Drugs 2002;62(Suppl. 2):1e9. Fant RV, Buchhalter AR, Buchman AC, Henningfield JE. Pharmacotherapy for tobacco dependence. Handb Exp Pharmacol; 2009:487e510. Field M, Mogg K, Bradley BP. Automaticity of smoking behaviour: the relationship between dual-task performance, daily cigarette intake and subjective nicotine effects. J Psychopharmacol 2006;20(6):799e805. Fregni F, Boggio PS, Santos MC, Lima M, Vieira AL, Rigonatti SP, et al. Noninvasive cortical stimulation with transcranial direct current stimulation in Parkinson’s disease. Mov Disord 2006;21:1693e702. Fregni F, Liguori P, Fecteau S, Nitsche MA, Pascual-Leone A, Boggio PS. Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: a randomized, sham-controlled study. J Clin Psychiatry 2008;69:32e40. Gallinat J, Lang UE, Jacobsen LK, Bajbouj M, Kalus P, von Haebler D, et al. Abnormal hippocampal neurochemistry in smokers: evidence from proton magnetic resonance spectroscopy at 3 T. J Clin Psychopharmacol 2007;27:80e4. Garavan H, Pankiewicz J, Bloom A, Cho JK, Sperry L, Ross TJ, et al. Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli. Am J Psychiatry 2000;157:1789e98. Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry 2002;159:1642e52. Hsu TY, Tseng LY, Yu JX, Kuo WJ, Hung DL, Tzeng OJ, et al. Modulating inhibitory control with direct current stimulation of the superior medial frontal cortex. Neuroimage 2011;56:2249e57. Hyman SE. Addiction: a disease of learning and memory. Am J Psychiatry 2005;162: 1414e22. Kessler SK, Turkeltaub PE, Benson JG, Hamilton RH. Differences in the experience of active and sham transcranial direct current stimulation. Brain Stimul 2011;5: 155e62. Klem GH, Lüders HO, Jasper HH, Elger C. The ten-twenty electrode system of the international federation. The international federation of clinical neurophysiology. Electroencephalogr Clin Neurophysiol Suppl 1999;52:3e6. Lang N, Nitsche MA, Paulus W, Rothwell JC, Lemon RN. Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability. Exp Brain Res 2004;156:439e43.

Z. Meng et al. / Journal of Psychiatric Research 54 (2014) 19e25 Lang N, Siebner HR, Ward NS, Lee L, Nitsche MA, Paulus W, et al. How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain? Eur J Neurosci 2005;22:495e504. McCarthy G, Luby M, Gore J, Goldman-Rakic P. Infrequent events transiently activate human prefrontal and parietal cortex as measured by functional MRI. J Neurophysiol 1997;77:1630e4. Miranda PC, Lomarev M, Hallett M. Modeling the current distribution during transcranial direct current stimulation. Clin Neurophysiol 2006;117:1623e9. Naqvi NH, Rudrauf D, Damasio H, Bechara A. Damage to the insula disrupts addiction to cigarette smoking. Science 2007;315:531e4. Nardone R, Bergmann J, Christova M, Caleri F, Tezzon F, Ladurner G, et al. Effect of transcranial brain stimulation for the treatment of Alzheimer disease: a review. Int J Alzheimers Dis 2012;2012:687909. Nitsche MA, Liebetanz D, Antal A, Lang N, Tergau F, Paulus W. Modulation of cortical excitability by weak direct current stimulationetechnical, safety and functional aspects. Suppl Clin Neurophysiol 2003;56:255e76. Nitsche MA, Niehaus L, Hoffmann KT, Hengst S, Liebetanz D, Paulus W, et al. MRI study of human brain exposed to weak direct current stimulation of the frontal cortex. Clin Neurophysiol 2004;115:2419e23. Nitsche MA, Paulus W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology 2001;57:1899e901. Nitsche MA, Paulus W. Transcranial direct current stimulation e update 2011. Restor Neurol Neurosci 2011;29:463e92. Nitsche MA, Seeber A, Frommann K, Klein CC, Rochford C, Nitsche MS, et al. Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex. J Physiol 2005;568:291e303.

25

Pathania VS. Women and the smoking epidemic: turning the tide. Bull World Health Organ 2011;89:162. Paulus MP, Tapert SF, Schuckit MA. Neural activation patterns of methamphetamine-dependent subjects during decision making predict relapse. Arch Gen Psychiatry 2005;62:761e8. Peto R, Lopez AD, Boreham J, Thun M, Heath C. Mortality from tobacco in developed countries: indirect estimation from national vital statistics. Lancet 1992;339: 1268e78. Piasecki TM. Relapse to smoking. Clin Psychol Rev 2006;26:196e215. Rose JE, McClernon FJ, Froeliger B, Behm FM, Preud’homme X, Krystal AD. Repetitive transcranial magnetic stimulation of the superior frontal gyrus modulates craving for cigarettes. Biol Psychiatry 2011;70:794e9. Sanders-Jackson AN, Cappella JN, Linebarger DL, Piotrowski JT, O’Keeffe M, Strasser AA. Visual attention to antismoking PSAs: smoking cues versus other attention-grabbing features. Hum Commun Res 2011;37:17. Singer MV, Feick P, Gerloff A. Alcohol and smoking. Dig Dis 2011;29:177e83. Suñer-Soler R, Grau A, Gras ME, Font-Mayolas S, Silva Y, Dávalos A, et al. Smoking cessation 1 year poststroke and damage to the insular cortex. Stroke 2012;43: 131e6. Waters AJ, Shiffan S, Sayette MA, Paty JA, Gwaltney CJ, Balabanis MH. Attentional bias predicts outcome in smoking cessation. Health Psychol 2003;22(4):378e 87. Zaehle T, Sandmann P, Thorne JD, Jäncke L, Herrmann CS. Transcranial direct current stimulation of the prefrontal cortex modulates working memory performance: combined behavioural and electrophysiological evidence. BMC Neurosci 2011;12:2.

Transcranial direct current stimulation of the frontal-parietal-temporal area attenuates smoking behavior.

Many brain regions are involved in smoking addiction (e.g. insula, ventral tegmental area, prefrontal cortex and hippocampus), and the manipulation of...
965KB Sizes 0 Downloads 4 Views