No abstract

The prefrontostriatal network is considered to play a key role in executive functions. Previous neuroimaging studies have shown that executive processes tested with card-sorting tasks requiring planning and set-shifting [e.g. Montreal-card-sorting-task (MCST)] may engage the dorsolateral prefrontal cortex (DLPFC) while inducing dopamine release in the striatum. However, functional imaging studies can only provide neuronal correlates of cognitive performance and cannot establish a causal relation between observed brain activity and task performance. In order to investigate the contribution of the DLPFC during set-shifting and its effect on the striatal dopaminergic system, we applied continuous theta burst stimulation (cTBS) to left and right DLPFC. Our aim was to transiently disrupt its function and to measure MCST performance and striatal dopamine release during [ 11 C]raclopride PET. A significant hemispheric asymmetry was observed. cTBS of the left DLPFC impaired MCST performance and dopamine release in the ipsilateral caudate-anterior putamen and contralateral caudate nucleus, as compared to cTBS of the vertex (control). These effects appeared to be limited only to left DLPFC stimulation while right DLPFC stimulation did not influence task performance or [ 11 C]raclopride binding potential in the striatum. This is the first study showing that cTBS, by disrupting left prefrontal function, may indirectly affect striatal dopamine neurotransmission during performance of executive tasks. This cTBS-induced regional prefrontal effect and modulation of the frontostriatal network may be important for understanding the contribution of hemisphere laterality and its neural bases with regard to executive functions, as well as for revealing the neurochemical substrate underlying cognitive deficits.

Drug-related cues induce craving, which may perpetuate drug use or trigger relapse in addicted individuals. Craving is also under the influence of other factors in daily life, such as drug availability and self-control. Neuroimaging studies using drug cue paradigms have shown frontal lobe involvement in this contextual influence on cue reactivity, but have not clarified how and which frontal area accounts for this phenomenon. We explored frontal lobe contributions to cue-induced drug craving under different intertemporal drug availability conditions by combining transcranial magnetic stimulation and functional magnetic resonance imaging in smokers. We hypothesized that the dorsolateral prefrontal cortex (DLPFC) regulates craving during changes in intertemporal availability. Subjective craving was greater when cigarettes were immediately available, and this effect was eliminated by transiently inactivating the DLPFC with transcranial magnetic stimulation. Functional magnetic resonance imaging demonstrated that the signal most proportional to subjective craving was located in the medial orbitofrontal cortex across all contexts, whereas the DLPFC most strongly encoded intertemporal availability information. The craving-related signal in the medial orbitofrontal cortex was attenuated by inactivation of the DLPFC, particularly when cigarettes were immediately available. Inactivation of the DLPFC also reduced craving-related signals in the anterior cingulate and ventral striatum, areas implicated in transforming value signals into action. These findings indicate that DLPFC builds up value signals based on knowledge of drug availability, and support a model wherein aberrant circuitry linking dorsolateral prefrontal and orbitofrontal cortices may underlie addiction.decision making | smoking | nicotine | expectancy | temporal discounting