A number of brain systems have been implicated in addictive behavior, but none have yet been shown to be necessary for maintaining the addiction to cigarette smoking. We found that smokers with brain damage involving the insula, a region implicated in conscious urges, were more likely than smokers with brain damage not involving the insula to undergo a disruption of smoking addiction, characterized by the ability to quit smoking easily, immediately, without relapse, and without persistence of the urge to smoke. This result suggests that the insula is a critical neural substrate in the addiction to smoking.Cigarette smoking, the most common preventable cause of morbidity and mortality in the developed world (1), is an addictive behavior. Despite being aware of negative consequences, many smokers have difficulty quitting, and even those who quit experience urges to smoke and tend to relapse (2, 3). These phenomena appear to arise from long-term adaptations within specific neural systems. Subcortical regions, such as the amygdala, the nucleus accumbens, and the mesotelencephalic dopamine system, have been shown in animal models to promote the self-administration of drugs of abuse (4, 5). Functional imaging studies have shown that exposure to drug-associated cues activates cortical regions such as the anterior cingulate cortex, the orbitofrontal cortex, and the insula (6-13). Among these regions, the insula is of particular interest because of its potential role in conscious urges. The insula has been proposed to function in conscious emotional feelings through its role in the representation of bodily (interoceptive) states (14-16). Activity within the insula on both sides of the brain has been shown to correlate with subjective cue-induced drug urges (7,8,11). It has also been shown that a high amount of activity in the right insula during a simple decision-making task is associated with relapse to drug use (17). Given its potential role in cognitive and emotional processes that promote drug use, the question arises as to whether the insula is necessary for maintaining addiction to smoking. We * To whom correspondence should be addressed: bechara@usc.edu. hypothesized that the insula is a critical neural substrate in the addiction to smoking. We predicted, therefore, that damage to the insula would disrupt addiction to smoking.We identified 19 cigarette smokers who had acquired brain damage that included the insula (18). Six of these patients had right insula damage, and 13 had left insula damage. We also identified a group of 50 cigarette smokers who had acquired damage that did not include the insula. All of these patients had been smoking more than five cigarettes per day for more than 2 years at the time of lesion onset. The groups were matched with respect to several characteristics, including the number of cigarettes they were smoking at lesion onset, the total number of years they had been smoking at lesion onset, and the etiology of their brain damage ( Fig. 1 and table S1).First, we performed a log...

Most prior research on the neurobiology of addiction has focused on the role of subcortical systems, such as the amygdala, the ventral striatum and mesolimbic dopamine system, in promoting the motivation to seek drugs. Recent evidence indicates that a largely overlooked structure, the insula, plays a crucial part in conscious urges to take drugs. The insula has been highlighted as a region that integrates interoceptive (i.e. bodily) states into conscious feelings and into decision-making processes that involve uncertain risk and reward. Here, we propose a model in which the processing of the interoceptive effects of drug use by the insula contributes to conscious drug urges and to decision-making processes that precipitate relapse.