Neuromodulation of reinforced skill learning reveals the causal function of prefrontal cortex

Hum Brain Mapp. 2018 Dec;39(12):4724-4732. doi: 10.1002/hbm.24317. Epub 2018 Jul 25.


Accumulating evidence has suggested functional interactions between prefrontal cortex (PFC) and dissociable large-scale networks. However, how these networks interact in the human brain to enable complex behaviors is not well-understood. Here, using a combination of behavioral, brain stimulation and neuroimaging paradigms, we tested the hypothesis that human PFC is required for successful reinforced skill formation. We additionally tested the extent to which PFC-dependent skill formation is related to intrinsic functional communication with this region. We report that inhibitory noninvasive transcranial magnetic stimulation over lateral PFC, a hub region with a diverse connectivity profile, causally modulated effective reinforcement-based motor skill acquisition. Furthermore, PFC-dependent skill formation was strongly related to the strength of functional connectivity between the PFC and regions in the sensorimotor network. These results point to the involvement of lateral PFC in the neural architecture that underlies the acquisition of complex skills, and suggest that, in relation to skill acquisition, this region may be involved in functional interactions with sensorimotor networks.

Keywords: functional MRI; motor learning; prefrontal cortex; reward; sequence learning; transcranial magnetic stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain Mapping / methods*
  • Cross-Over Studies
  • Female
  • Histidine Kinase / physiology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Motor Skills / physiology*
  • Nerve Net / physiology*
  • Prefrontal Cortex / physiology*
  • Random Allocation
  • Reinforcement, Psychology*
  • Serial Learning / physiology*
  • Transcranial Magnetic Stimulation / methods*
  • Young Adult


  • Histidine Kinase