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Background Nicotine is primarily rsponsible for the highly addictive properties of cigarettes.Similar to other substances,nicotine dependence is related to many important brain regions,particular in mesolimbic reward circuit.This study was to further reveal the alteration of brain function activity during resting state in chronic smokers by fractional amplitude of low frequency fluctuation (fALFF) based on functional magnetic resonance imaging (fMRI),in order to provide the evidence of neurobiological mechanism of smoking.Methods This case control study involved twenty healthy smokers and nineteen healthy nonsmokers recruited by advertisement.Sociodemographic,smoking related characteristics and fMRI images were collected and the data analyzed.Results Compared with nonsmokers,smokers showed fALFF increased significantly in the left middle occipital gyrus,left limbic lobe and left cerebellum posterior lobe but decreases in the right middle frontal gyrus,right superior temporal gyrus,right extra nuclear,left postcentral gyrus and left cerebellum anterior lobe (cluster size ＞100 voxels).Compared with light smokers (pack years ≤20),heavy smokers (pack years ＞20) showed fALFF increased significantly in the right superior temporal gyrus,right precentral gyrus,and right occipital lobe/cuneus but decreased in the right/left limbic lobe/cingulate gyrus,right/left frontal lobe/sub gyral,right/left cerebellum posterior lobe (cluster size ＞50 voxels).Compared with nonsevere nicotine dependent smokers (Fagerstr(o)m test for nicotine dependence,score ≤6),severe nicotine dependent smokers (score ＞6) showed fALFF increased significantly in the right/left middle frontal gyrus,right superior frontal gyrus and left inferior parietal lobule but decreased in the left limbic lobe/cingulate gyrus (duster size ＞25 voxels).Conclusions In smokers during rest,the activity of addiction related regions were increased and the activity of smoking feeling,memory,related regions were also changed.The resting state activity changes in many regions were associated with the cumulative amount of nicotine intake and the severity of nicotine dependence.