The objective of this work was to use a data driven analysis technique to find different patterns of rsFNC characterizing groups of subjects who smoke, drink or both. The data driven nature of our approach reduced possible bias present in seed-based analyses. Obtained results do not invalidate some of the previously reported observations using a-priori regions of interests (Camchong et al., 2012, 2013; Claus et al., 2011; Hong et al., 2009), but instead reveal the strongest effects found in the population under study. The observed general pattern describes a hypo-connectivity in substance dependence subjects compared to controls. The hypo-connectivity was prominent between visual RSNs connected to sensorimotor, salience and precuneus RSNs. On the contrary, hyper-connectivity observations were few, but pointing to important brain regions including the DMN, precuneus and putamen. Results suggest that nicotine and alcohol produce both similar and distinctive effects in brain connectivity indicating the possibility of disentangling rsFNC dysfunctions related to alcohol use disorder from those associated to nicotine dependence. An increase in the connectivity between DMN and precuneus was found to be an important feature that
