Figure 6.

Proposed model of brain circuitry driving nicotine use in schizophrenia. We observed default mode network (DMN) hyperconnectivity in our sample of individuals with schizophrenia, consistent with prior literature (33). We also observed that acute nicotine administration normalized DMN hyperconnectivity in schizophrenia. Based on this data, we hypothesize that individual variation in the magnitude of this DMN disruption gives rise to: (a) variation in the severity of network disorganization and (b) variation in severity of nicotine use. We propose that the DMN mediates the relationship between nicotine use and cognition in schizophrenia. DMN hyperconnectivity is linked to poor attentional performance (45) and, in healthy controls, nicotine can both reduce DMN connectivity and improve attention (11). We propose that DMN connectivity mediates the relationship between nicotine use and attentional performance and that disruption of this network in schizophrenia drives the need for nicotine to correct network pathology (and cognition).