A temporal chronnectomic framework: Cigarette smoking preserved the prefrontal dysfunction in schizophrenia

The widespread cigarette smoking behavior in schizophrenia is generally attributed to its alleviation of patients' symptomatology by the self-medication hypothesis. The prefrontal cortex (PFC), which predominantly supports orchestrating thoughts and actions, might underlie the biological underpinnings of smoking behavior in schizophrenia. However, few studies have focused on the impact of smoking on the prefrontal function in schizophrenia. This study assumed that smoking-related alterations on the prefrontal dynamics of information integration (chronnectome) were different between healthy control (HC) and schizophrenia patient (SP). We recruited SP smokers (N = 22)/nonsmokers (N = 27) and HC smokers (N = 22)/nonsmokers (N = 21) who underwent resting-state functional magnetic resonance imaging (rsfMRI) with a total of 240 volumes (lasting for 480 s). We employed a chronnectomic density analysis on the rsfMRI signal by using a sliding-window method. We examined the interaction effect between smoking status and diagnosis utilizing two-way analysis of covariance under permutation test. Whereas disease-related reduced effects were found on the bilateral dorsolateral PFC chronnectomic density, no smoking effect was observed. As regards interaction effect, a smoking-related reduced effect was found on the right dorsolateral PFC chronnectomic density in HC, while a smoking-related increased effect was observed in SP. Nevertheless, post-hoc analysis revealed significant group difference between SP smokers and HC nonsmokers. Therefore, these results indicated a smoking-related preservation effect on disrupted prefrontal dynamics in schizophrenia that cannot restore it to normal levels. The novel findings yield a prefrontal-based chronnectome framework to elaborate upon the self-medication hypothesis in schizophrenia.