Previous neuroimaging studies have shown that executive processes requiring planning and set-shifting [e.g. Montreal card sorting task (MCST)] may engage the dorsolateral prefrontal cortex (DLPFC) while inducing dopamine (DA) 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 DAergic 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 DA release during [11C]raclopride PET. cTBS of the left DLPFC impaired MCST performance and DA release in the ipsilateral caudate–anterior putamen and contralateral caudate, as compared to cTBS of the vertex (control). These effects were limited only to left DLPFC stimulation but not right DLPFC. This is the fi rst study showing that cTBS, by disrupting left DLPFC function, may indirectly affect striatal DA release 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 defi cits.
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