For the imaging study, images were reconstructed and analyzed as previously described including a nonuniform attenuation correction (25). We chose brain regions that were known to express α4β2 nAChRs, including frontal, parietal, anterior cingulate, temporal and occipital cortices, thalamus, striatum (an average of caudate and putamen) and cerebellum. The outcome measure VT/fP (regional activity divided by free plasma parent between 6 and 8 hours) was used (38). For each rare variant carrier, the availability of α4β2 nAChRs was compared to a group of 4 to 6 age- and smoking status-matched non-carriers.
