A consideration of the brain regions involved in affective regulation, executive function, and autonomic reactivity suggests a primary role for the limbic, cerebellothalamocortical, and HPA systems. These regions may play an important role as neural underpinnings of risk for AUD. The cerebellum, thalamus, hypothalamus, and regions of the prefrontal cortex are particularly susceptible to alcohol (Harper et al. 2003; reviewed by Harper and Matsumoto 2005), and the interconnected circuits among these systems define the neural substrates of intrinsic motivation, reinforcement, and reward in addiction (Koob 1996, 2003). The forthcoming discussion describes components of these overlapping systems that have been found to be vulnerable in individuals at risk for AUD.
