Brain regions related to tool use and action knowledge reflect nicotine dependence

In addition to reward- and craving-related processes, habitual mechanisms play an important role in addiction. While the dorsal striatum has been proposed to code for the motivational state of habitual drug-seeking actions, the neural underpinnings of the corresponding drug-taking skills and action knowledge remain poorly understood. We used functional magnetic resonance imaging (fMRI) and a behavioral orientation affordance paradigm to investigate the neural and behavioral correlates of automatized drug-taking actions in nicotine dependence. Smokers exhibited higher fMRI activations than nonsmokers when viewing smoking-related but not when viewing control images. These group differences in fMRI activations were located not only in brain regions associated with craving and habitual learning (left ventral and dorsal striatum, dorsolateral prefrontal cortex, insula, uncus, medial frontal gyrus, right subcallosal gyrus, and bilateral parahippocampal gyrus), but also in a network of brain regions which has been strongly implicated in the encoding of action knowledge and tool use skills (bilateral premotor cortex, left superior parietal lobule, and right lateral cerebellum). A behavioral affordance reaction-time task indicated that smokers, but not nonsmokers, showed an automatized responsiveness to smoking paraphernalia similar to everyday objects. Moreover, smokers showed strong intercorrelations between fMRI activations in tool use-related brain regions, behavioral responsiveness to smoking-related cues, and severity of nicotine dependence. Apparently smoking-related action representations in smokers are stored in brain regions typically representing tool use skills and action knowledge. Most importantly, cortical and behavioral correlates of the respective drug-taking skills vary with the individual degree of nicotine dependence.