Given the discussion above, it is not surprising that the insula appears to play a pivotal role in nicotine addiction. Critically, damage to the insula can result in a sudden and profound disruption of smoking behavior (Naqvi et al., 2007). Further supporting insula’s involvement, a recent study observed greater grey matter density in the anterior insula of smokers in comparison to non-smokers (Fig 6A; Zhang et al., 2011). Additionally, when deprived of nicotine, elevated activity in the insula, along with other brain regions, covaries with increased abstinence-induced smoking urges (Wang et al., 2007). Multiple studies of cigarette-cue reactivity have noted positive associations between insula responses and subjective use-urges (Naqvi and Bechara, 2009). Connecting insula activity with attentional processes, Janes and colleagues (2010) reported that attentional bias for smoking-related stimuli assessed in a Stroop task variant was positively correlated with greater insula cue-reactivity (Fig 6B). Conversely, during performance of a sustained attention task not involving drug-related stimuli, nicotine administered to minimally-deprived smokers decreased insula activity while also improving performance (Fig 6C; Lawrence et al., 2002). Thus, we propose that insula hyperactivity
