In line with our hypothesis we found higher cue-induced activation of the ventral striatum in social compared to heavy drinkers, and higher dorsal striatal activation in heavy drinkers. Increased prefrontal activation may indicate that social drinkers activate cortical control when viewing alcohol cues, which may prevent the development of heavy drinking or alcohol dependence. Our results suggest differentiating treatment research depending on whether alcohol use is hedonic or compulsive.

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There has been tremendous progress in the development of imaging technologies. Use of these technologies has clearly demonstrated the structural and functional brain abnormalities that can occur with chronic alcohol use. The study of the alcoholic brain provides an heuristic model which furthers our understanding of neurodegenerative changes in general, as well as their partial reversibility with sustained abstinence. Additionally, functional imaging is poised to become an important tool for generating predictions about individual brain functioning, which can then be used as a basis for personalized medicine.

Our study suggests that severity of nicotine dependence and intensity of craving are independently associated with cue-induced brain activation in separate neuronal networks. The observed association between severity of dependence and brain activity in regions involved in allocation of attention, motor preparation and imagery might reflect preparation of automated drug taking behavior thereby facilitating cue-induced relapse.

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Emotional reactivity and regulation are fundamental to human behavior. As inter-individual behavioral variation is affected by a multitude of different genes, there is intense interest to investigate gene-gene effects. Functional sequence variation at two genes has been associated with response and resiliency to emotionally unpleasant stimuli. These genes are the catechol-O-methyltransferase gene (COMT Val 158 Met) and the regulatory region (5-HTTLPR) of the serotonin transporter gene. Recently, it has been proposed that 5-HTT expression is not only affected by the common S/L variant of 5-HTTLPR but also by an A to G substitution. Using functional magnetic resonance imaging, we assessed the effects of COMT Val 158 Met and both 5-HTT genotypes on brain activation by standardized affective visual stimuli (unpleasant, pleasant, and neutral) in 48 healthy subjects. Based on previous studies, the analysis of genotype effects was restricted to limbic brain areas. To determine allele-dose effects, the number of COMT Met 158 alleles (i.e., lower activity of COMT) and the number of 5-HTT low expressing alleles (S and G) was correlated with the blood oxygen level-dependent (BOLD) response to pleasant or unpleasant stimuli compared to neutral stimuli. We observed an additive effect of COMT and both 5-HTT polymorphisms, accounting for 40% of the interindividual variance in the averaged BOLD response of amygdala, hippocampal and limbic cortical regions elicited by unpleasant stimuli. Effects of 5-HTT and COMT genotypes did not affect brain processing of pleasant stimuli. These data indicate that functional brain imaging may be used to assess the interaction of multiple genes on the function of neuronal networks.

No abstract

Smoking-related cues elicit craving and mesocorticolimbic brain activation in smokers. Severity of nicotine dependence seems to moderate cue reactivity, but the direction and mechanisms of its influence remains unclear. Although tobacco control policies demand a ban on tobacco advertising, cue reactivity studies in smokers so far have not employed tobacco advertisement as experimental stimuli. We investigated whether tobacco advertisement elicits cue reactivity at a behavioral (subjective craving) and a neural level (using functional magnetic resonance imaging) in 22 smokers and 21 never-smokers. Moreover, we studied the influence of severity of dependence on cue reactivity. In smokers, tobacco advertisement elicited substantially more craving than control advertisement whereas never-smokers reported no cue induced craving. Surprisingly, neuronal cue reactivity did not differ between smokers and never-smokers. Moderately dependent smokers' craving increased over the course of the experiment, whereas highly dependent smokers' craving was unaffected. Moderately dependent smokers' brain activity elicited by tobacco advertisement was higher in the amygdala, hippocampus, putamen and thalamus compared with highly dependent smokers. Furthermore, limbic brain activation predicted picture recognition rates after the scanning session, even in never-smokers. Our findings show that tobacco advertisement elicits cigarette craving and neuronal cue reactivity primarily in moderately dependent smokers, indicating that they might be particularly responsive towards external smoking-related cues. On the other hand, neuronal cue reactivity and cigarette craving in highly dependent smokers is more likely triggered by internal cues such as withdrawal symptoms. Tobacco advertisement seems to likewise appeal to smokers and non-smokers, clarifying the potential danger especially for young non-smokers.