Verbal instructions are central to humans' capacity to learn new behaviors with minimal training, but the neurocognitive mechanisms involved in verbally instructed behaviors remain puzzling. Recent functional magnetic resonance imaging (fMRI) evidence suggests that the right middle frontal gyrus and dorsal premotor cortex (rMFG-dPMC) supports the translation of symbolic stimulus–response mappings into sensorimotor representations. Here, we set out to (1) replicate this finding, (2) investigate whether this region's involvement is specific to novel (vs. trained) instructions, and (3) study whether rMFG-dPMC also shows differences in its (voxel) pattern response indicative of general cognitive processes of instruction implementation. Participants were shown instructions, which they either had to perform later or merely memorize. Orthogonal to this manipulation, the instructions were either entirely novel or had been trained before the fMRI session. Results replicate higher rMFG-dPMC activation levels during instruction implementation versus memorization and show how this difference is restricted to novel, but not trained, instruction presentations. Pattern similarity analyses at the voxel level further reveal more consistent neural pattern responses in rMFG-dPMC during the implementation of novel versus trained instructions. In fact, this more consistent neural pattern response seemed to be specific to the first instruction presentation and disappeared after the instruction had been applied once. These results further support a role of rMFG-dPMC in the implementation of novel task instructions and highlight potentially important differences in studying this region's gross activation levels versus (the consistency of) its response patterns.

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