Because of nicotine’s cognitive-enhancing effects in schizophrenia at the α7 nicotinic receptor, many clinical trials explored the use of nicotine and α7 nicotinic agonists as a treatment for cognitive deficits in schizophrenia.6 However, these studies found that nicotine and α7 nicotinic agonists were not an effective cognitive enhancement therapy. These conflicting findings beg the question: what is the underlying neural mechanism of nicotine? Is it possible that, in addition to acting upon reward circuitry, nicotine also acts on schizophrenia-specific circuitry? To answer this question, we used an entirely data-driven approach to identify neural correlates of nicotine use in schizophrenia.7 This approach is not confined by a predetermined hypothesis of what brain regions will be involved. Instead, a data-driven approach allows us to examine the entire brain and ask, “where is brain activity related to nicotine use?” Using this data-driven method, we observed that brain network organization was related to nicotine use, but only in schizophrenia. Specifically, only in individuals with schizophrenia, those who smoked more cigarettes per day showed a pathologic expansion of the default mode network (DMN) into a region typically occupied by a different network. PSYCHIATRIC TIMES.