Our paradigm was modified from earlier auditory P3 studies (Knight, 1984, 1996; Knight et al., 1989) on patients with cortex lesions. Interestingly, prefrontal lesions seemed to cause a pattern of P3 changes, a reduced novel-sound P3 at frontal sites and a normal target P3 (Knight, 1984), which resembles our P3 findings associated with adolescent alcohol use. Previous studies suggest that the maturation of prefrontal association areas continues (at least) until the early 20s (e.g., Sowell et al., 1999), and these regions could, thus, be specifically vulnerable to the effects of early-onset ethanol use (Clark et al., 2008; De Bellis et al., 2005; Lubman et al., 2007). Accordingly, we suggest that the correlation between adolescent alcohol use and novel P3 amplitude could be related to prefrontal dysfunctions. Consistent with this interpretation, the negative correlation between novel P3 amplitude and alcohol use was specifically significant in the frontal electrode sites, while the inherited effects were more predominant parietal.
