The effects of lesions in the ventromedial prefrontal cortex and related areas on emotional responses to cigarette smoking

Cigarette smoking is an addictive behavior. There are two learned emotional responses to smoking that may be particularly important for promoting addiction to smoking: the pleasure obtained from the airway sensory effects of smoking (airway sensory pleasure) and the urge to smoke that is elicited by environmental smoking cues (cue-induced urge). The ventromedial prefrontal cortex (VMPFC) has been implicated in a variety of learned emotional and motivational responses to drug-associated sensory cues. This project set out to address the role of the VMPFC and related areas in airway sensory pleasure and cue-induced urge, as well as the role of this region in promoting smoking behavior in real life, by examining the effects of focal lesions within the VMPFC and related areas in human cigarette smokers. It was found that lesions of the VMPFC itself were associated with a marked impairment of cue-induced urge in the laboratory, which was paralleled by a reported reduction in the difficulty of abstaining from smoking in real life. At the same time, VMPFC lesions led to a relative sparing of airway sensory pleasure in the laboratory, which was paralleled by no change in the enjoyment from smoking in real life. In addition, it was found that VMPFC lesions were not associated with changes in real-life measures of smoking dependence. It was found that lesions of the insula, a region that is functionally related to the VMPFC, were associated with an ability to quit smoking easily, immediately, without relapses and without a lasting urge to smoke. However, among patients with insula lesions who continued to smoke after lesion onset, there were no appreciable impairments of airway sensory pleasure or cue-induced urge. 1