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 following nicotine-abstinence or in response to smoking-related cues may precipitate decreased cognitive performance. Such a view is consistent with previous proposals relating insula dysfunction with other neuropsychiatric disorders such as anxiety (hyperactivity: Paulus & Stein, 2006) and autism spectrum disorders (hypoactivity: Uddin and Menon, 2009).
