Temporal dynamic changes of intrinsic brain activity in schizophrenia with cigarette smoking

Mounting evidence from multimodal neuroimaging studies has supported a neurobiological basis for schizophrenia-nicotine dependence comorbidity. However, this evidence comes exclusively from studies measuring static intrinsic activity/connectivity of the brain, while the dynamic effects of this comorbidity remain poorly understood. The current study therefore sought to examine whether temporal dynamic intrinsic brain activity interacted with diagnosis (schizophrenics vs. healthy controls) and smoking status (smokers vs. non-smokers). We used a mixed sample design and included the following four groups: i) schizophrenic smokers (n = 22), ii) schizophrenic non-smokers (n = 27), iii) healthy control smokers (n = 22), and iv) healthy control non-smokers (n = 21). All subjects underwent functional magnetic resonance imaging during the resting state. The temporal variability in intrinsic brain activity among the four groups was compared using a novel dynamic amplitude of low-frequency fluctuation (dALFF) method. A significant main effect of diagnosis was found in the left superior parietal gyrus (SPG; F(1, 88) = 142.1, P < 0.0001). Moreover, the dALFF strength in the SPG was positively correlated with disease duration in patients with schizophrenia (Rho(46) = 0.43, P = 0.002). In addition, a significant interaction between diagnosis and smoking status was observed in the left dorsolateral prefrontal cortex (DLPFC; F(1, 88) = 7.39, P = 0.008), which was consistent with the self-medication hypothesis. Together, this study has demonstrated for the first time that nicotine restores dynamic intrinsic brain activity in the left DLPFC in patients with schizophrenia. This interaction may be a clinical neuromarker for increased comorbid smoking in schizophrenia.