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Conversely, individuals with high PEM/E , low NEM/N and low AI would be least vulnerable (most resilient) to SUD ( Figure 3 To our initial analysis, we added CI as an additional personality trait, modulated by a circuit including glutamatergic neurons from the ventromedial prefrontal cortex and the posterior cingular cortex that innervate the ventral striatum (nucleus accumbens) and, as with AI , is also moderated by the D 4 R gene, and by the gene of the enzyme catechol- O -methyltransferase ( Figure 3 )