The preponderance of the data suggests that the externalizing pathway to alcohol dependence may be partially determined by variation in the functioning of circuitry involved in executive control and behavioral inhibition that includes connectivity of the cerebellum, thalamus, and prefrontal cortex which generates a cortico-thalamo-cerebellar feedback loop. This circuitry has also been implicated in frequently co-occurring conditions including ADHD (Nigg and Casey 2005). The internalizing pathway is associated with mood problems, negative affect, and a hypersensitivity to rewards/stress reflective of alterations in the OFC, extended amygdala, hypothalamus, and the HPA system. Impairments in emotional conditioning due to abnormalities of the extended limbic network (including hippocampal and hypothalamic feedback of the HPA system) have been postulated in developmental models of ASPD (Blair 2001; Blair et al. 2006; Crowe and Blair 2008; Susman 2006) and affective disorders (Monk 2008). The neural circuits of the internalizing and externalizing pathways are highlighted in Fig. 4. Notably, the pathways are interconnected and further communicate through the cingulate gyrus and insular cortex.
