of non-drug rewards, hypofrontality could have consequences for difficulty in guiding behavior to obtain these rewards as necessary for healthy functioning [11]. Second, another possibility is that hypofrontality is particularly evident in the context of response to non-drug or natural rewards in addiction, because reward circuitry adapts to focus on drug rewards at the expense of non-drug rewards. Consistent with this possibility, studies of alcohol dependence have revealed an opposite pattern of response to alcohol-related and non-alcohol-related stimuli in addiction. Specifically, it appears that in comparison with healthy adults, alcohol-dependent adults exhibit greater response in reward-related regions to alcohol-related reward [16], [17], [18], [19], but decreased response to monetary (i.e., non-drug) reward [20], [21]. Furthermore, response in the mPFC and VS to alcohol-related reward predict relapse among detoxified alcohol-dependent adults [22]. Through either process, reduced coupling of prefrontal cortical regions from the ventral striatum has been hypothesized to diminish and enhance the capacity of the prefrontal cortex to initiate behaviors in response to natural and alcohol-related reward stimuli, respectively, which in turn drives the cycle of addiction [11].
