Cigarette use has been associated with size reductions across several brain structures. Reduced cell numbers, increased markers of apoptosis and alterations in synaptic activity in the neocortex, hippocampus, midbrain and cerebellum have been observed in adult rats exposed to nicotine (Chen et al. 2003; Trauth et al. 2000; Trauth et al. 1999; Xu et al. 2001). A case-control study comparing smokers to non-smokers reported smaller volumes in the prefrontal and anterior cingulate cortices as well lower gray matter density in the cerebellum of smokers (Brody et al. 2004). Smokers had reduced gray matter volumes or densities in portions of frontal lobe subregions, occipital cortex, cuneus, precuneus, and the thalamus compared to never-smokers. Smokers were also found to have a negative correlation between frontal lobe gray matter volume and cigarette pack-years (Gallinat et al. 2006).