We assessed time-dependent neuronal activity accompanying learning using fu
nctional magnetic resonance imaging (fMRI). An artificial grammar learning
paradigm enabled us to dissociate activations associated with individual it
em learning from those involved in learning the underlying grammar system.
We show that a localized region of right prefrontal cortex (PFC) is prefere
ntially sensitive to individual item learning during the early stages of th
e experiment, while the left PFC region is sensitive to grammar learning wh
ich occurred across the entire course of the experiment. In addition to dis
sociating these two types of learning, we were able to characterize the eff
ect of rule acquisition on neuronal responses associated with explicit lear
ning of individual items. This effect was expressed as modulation of the ti
me-dependent right PFC activations such that the early increase in activati
on associated with item learning was attenuated as the experiment progresse
d. In a further analysis we used structural equation modelling to explore t
ime-dependent changes in inter-regional connectivity as a function of both
item and grammar rule learning. Although there were no significant effects
of item learning on the measured path strengths, rule learning was associat
ed with a decrease in right fronto parietal connectivity and an increase in
connectivity between left and right PFC. Further fronto-parietal path stre
ngths were observed to change, with an increase in left fronto-parietal and
a decrease in right fronto-parietal connectivity. path strength from right
PFC to left parietal cortex, We interpret our findings in terms of a left
frontal system mediating the semantic analysis of study items and directly
influencing a right fronto parietal system associated with episodic memory
retrieval.