Prefrontal regulation of neuronal pain systems during expectation-induced changes in perceived pain

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A growing number of lesion and neuroimaging studies highlight the critical role played by the dorsolateral prefrontal cortex (DLPFC) in producing planned, organized, and well-regulated behaviour. However, its contribution to the organization and representation of pain in the brain remains elusive. We argue, based on evidence from multiple disciplines, that DLPFC activity occurs hierarchically upstream from classical pain processing regions of the brain and that it serves to regulate cerebral pain circuits based on intrinsic and/or extrinsic (environmental) demands. The DLPFC, therefore, should play a key role in shaping expectation-induced changes in pain experiences. This research program proposes to investigate the role of the DLPFC on the encoding and subsequent reloading of pain expectations. It will also seek to identify how the DLPFC regulates downstream pain neurocircuitry by studying its influence on pain-evoked cortical activity and functional connectivity. Different methodological means will be used, including brain imaging with electroencephalography and disruption of DLPFC function with repetitive transcranial magnetic stimulation. A better understanding of the behavioral and cerebral modulation of pain by the DLPFC will provide key insights into how the brain transforms expectations of relief into actual experiences of analgesia and how separate brain regions work together to form functionally-coherent networks.