Our findings show that adolescent light smokers exhibit brain activation in response to smoking cues and these areas of brain activation are similar to those observed in adult smokers. More specifically, the increased BOLD activations observed in the left anterior cingulate, bilateral middle occipital gyri and right hippocampus in the whole brain analysis of our light smokers have all been reported in adult and heavy teen smokers [7
]. Based on both animal and human studies, [27
] all of these regions are thought to play a significant role in nicotine addiction [29
Activation of the hippocampus is thought to be involved with drug reward, drug-related memories and conditioned responses [33
] whereas activation of the anterior cingulate gyrus is thought to be involved in compulsive drug use and poor inhibitory control [34
]. In our study, activation within this region was highly correlated with both number of cigarettes smoked per day and self-reported addiction on a 0-100% scale. Interestingly, there was no association between activation in the anterior cingulate and score on the mFTQ. This finding is consistent with prior findings by our team [35
] that the mFTQ may a less sensitive measure of early signs of addiction in adolescent light smokers than self-reported level of addiction. We also found a high correlation between craving and activation within the middle occipital gyri, again similar to studies in heavy smoking addicted adults. The middle occipital region is modulated by visual attention, and activation in response to smoking cues within this region has been correlated with both nicotine craving and addiction [6
A significant number of our participants reported histories of other substance use in addition to smoking cigarettes. Although alcohol and marijuana act on similar substrates within the mesocorticolimic regions of the brain as nicotine, neither self-reported alcohol nor marijuana use was associated with increased activation to smoking cues. However, it is possible that marijuana smoking may affect cigarette-cue responsivity in ways which are beyond the scope of this study. Further research needs to be undertaken to tease apart these effects.
In our a priori ROI analyses we found significant activation to smoking cues in several key areas within the mesocorticolimic system including the amygdala, anterior cingulate, hippocampus and the medial orbital frontal region. All of these regions have been associated with responses to drug-related stimuli in adults [6
] and are thought to play a role in reward-related learning [38
], impulse control, salience attribution [34
], and compulsive drug use [29
]. However, we did not find significant activity in some other areas reported in adult smoking studies (e.g., insula, fusiform, thalamus, and temporal regions). Perhaps we found no significant associations with these additional areas because these other areas become activated at a later “stage” of addiction and thus are not activated in light smokers. Clearly, more research needs to be done in this area, including the direct comparison of adolescent light smokers to adult light and heavy smokers.
Importantly, non-smokers did not show activation in response to smoking cues in any areas in the whole brain analyses or in the ROIs selected as part of the a priori analyses. In the between group analyses, whole brain and a priori ROI, the contrasts between smokers and non-smokers did not reach statistical significance. We suspect that this lack of significance may stem from an increased variability of neural responsivity to smoking cues within the non-smoking group which may be teased out with a small larger size. Another limitation to this study was the necessity of allowing the smokers to smoke during the day prior to the scan, which may have blunted their cue reactivity. However, we found no correlation between activation and time since last cigarette. In addition, using a similar fMRI paradigm, McClernon et al. [6
] found that abstinence did not result in larger responses to smoking cues.