Abstract
BackgroundBrain dopamine is implicated in the regulation of movement, attention, reward and learning and plays an important role in Parkinson's disease, schizophrenia and drug addiction. Animal experiments have demonstrated that brain stimulation is able to induce significant dopaminergic changes in extrastriatal areas. Given the up-growing interest of non-invasive brain stimulation as potential tool for treatment of neurological and psychiatric disorders, it would be critical to investigate dopaminergic functional interactions in the prefrontal cortex and more in particular the effect of dorsolateral prefrontal cortex (DLPFC) (areas 9/46) stimulation on prefrontal dopamine (DA).Methodology/Principal FindingsHealthy volunteers were studied with a high-affinity DA D2-receptor radioligand, [11C]FLB 457-PET following 10 Hz repetitive transcranial magnetic stimulation (rTMS) of the left and right DLPFC. rTMS on the left DLPFC induced a significant reduction in [11C]FLB 457 binding potential (BP) in the ipsilateral subgenual anterior cingulate cortex (ACC) (BA 25/12), pregenual ACC (BA 32) and medial orbitofrontal cortex (BA 11). There were no significant changes in [11C]FLB 457 BP following right DLPFC rTMS.Conclusions/SignificanceTo our knowledge, this is the first study to provide evidence of extrastriatal DA modulation following acute rTMS of DLPFC with its effect limited to the specific areas of medial prefrontal cortex. [11C]FLB 457-PET combined with rTMS may allow to explore the neurochemical functions of specific cortical neural networks and help to identify the neurobiological effects of TMS for the treatment of different neurological and psychiatric diseases.
Highlights
Brain dopamine (DA) is implicated in the regulation of movement, attention, reward and learning [1,2,3] and plays an important role in Parkinson’s disease, schizophrenia and drug addiction [4,5]
The same stimulation paradigm applied over the right dorsolateral prefrontal cortex (DLPFC) did not induce any detectable changes in [11C]FLB 457 binding potential (BP) in the medial prefrontal cortex or other cortical regions
Individual BPs extracted from ROI centered at the statistical peak defined by the parametric maps confirmed these findings and showed significant BP reduction following left but not right DLPFC repetitive transcranial magnetic stimulation (rTMS) (Table 2 and Figure 2)
Summary
Brain dopamine (DA) is implicated in the regulation of movement, attention, reward and learning [1,2,3] and plays an important role in Parkinson’s disease, schizophrenia and drug addiction [4,5]. Animal experiments have demonstrated that brain stimulation is able to induce significant dopaminergic changes in extrastriatal cortical areas [10,15,16,17,18]. Given the up-growing interest of non-invasive brain stimulation as potential tool for treatment of neurological and psychiatric disorders [19,20,21], it would be critical to investigate dopaminergic functional interactions in the prefrontal cortex and in particular the effect of dorsolateral prefrontal cortex (DLPFC) (areas 9/46) stimulation on prefrontal dopamine. Given the up-growing interest of noninvasive brain stimulation as potential tool for treatment of neurological and psychiatric disorders, it would be critical to investigate dopaminergic functional interactions in the prefrontal cortex and more in particular the effect of dorsolateral prefrontal cortex (DLPFC) (areas 9/46) stimulation on prefrontal dopamine (DA)
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