Contextual cues modulate via dorsolateral prefrontal cortex a network of brain regions underlying enhanced cigarette craving

Drug addictions constitute one of the most substantial societal and medical problems of our time. While early on a lot of effort was put into investigation of the mechanisms underlying drug dependency (i.e., the addicted person not being able to stop taking the drug in fear of withdrawal symptoms), it has become obvious that craving for the drug (i.e., overwhelming desire that drives one to take the drug even if one realizes it is harmful) is the mechanism that sustains the addiction by predisposing afflicted individuals to relapses even after withdrawal symptoms have subsided. Craving plays a key role in development of addiction to legal drugs such as alcohol and tobacco and, although these are not as strong as illicit drugs in their addicting effects, they share the same basic mechanisms in that prolonged use leads to both development of dependency and craving. Craving is further enhanced when the addicted person sees the drug he/she is addicted to, however, there have been few neuroimaging studies mapping brain mechanisms that underlie enhancement of craving by such contextual cues.

In their recent study, Hayashi et al. (2013) ten healthy heavy smokers underwent four fMRI scanning sessions where they were shown alternating 2-min neutral movie clips and 2-min clips depicting smoking. Behavioral ratings of craving increased when watching the smoking clips, especially when the subjects were aware that smoking would be possible immediately after the experiment, and enhanced activity in several cortical areas, most robustly medial orbitofrontal cortex, was associated with these cue-related craving effects.  Inactivation of left dorsolateral prefrontal cortex with transcranial magnetic stimulation for ~30 minutes prior to onset of the neuroimaging session eliminated the effects of knowing that the drug will be available immediately after scanning on the subjective craving, medial orbitofrontal cortex activation, and functional connectivity between dorsolateral prefrontal cortex and medial orbitofrontal cortex, ventral striatum, and anterior cingulate cortex.

These findings nicely demonstrate the role of dorsolateral prefrontal cortex in a network of brain areas that give rise to enhanced cigarette craving by contextual cues. The findings further provide a link between the areas of addiction research and decision making, as the authors successfully model their findings in the context of economic decision making theory where addiction can be viewed as steep temporal discounting (i.e., addicted individuals place greater value on immediate vs. delayed rewards) and shed light on the underlying cerebral mechanisms. This highly exciting study also demonstrates how transcranial magnetic stimulation can be utilized to produce long-lasting (up to 30 min) focal cortical inactivation, the effects of which can then be inspected using functional magnetic resonance imaging and associated behavioral measures.

Reference: Hayashi T, Koa IH, Strafella AP, Daghera A. Dorsolateral prefrontal and orbitofrontal cortex interactions during self-control of cigarette craving. Proceedings of the National Academy of Sciences USA (2013) e-publication ahead of print. http://dx.doi.org/10.1073/pnas.1212185110

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