Differential hippocampal and prefrontal-striatal contributions to instance-based and rule-based learning

It is a topic of current interest whether learning in humans relies on the acquisition of abstract rule knowledge (rule-based learning) or whether it depends on superficial item-specific information (instance-based learning). Here, we identified brain regions that mediate either of the two learning mechanisms by combining fMRI with an experimental protocol shown to be able to dissociate both learning mechanisms. Subjects had to learn object-position conjunctions in several trials and blocks. In a learning condition, either objects (Experiment 1) or positions (Experiment 2) were held constant within-blocks. In contrast to a control condition in which object–position conjunctions were trial-unique, a performance increase within and across-blocks was observed in the learning condition of both experiments. We hypothesized that within-block learning mainly relies on instance-based processes, whereas across-block learning might depend on rule-based mechanisms. A within-block parametric fMRI analysis revealed a learning-related increase of lateral prefrontal and striatal activity and a learning-related decrease of hippocampal activity in both experiments. By contrast, across-block learning was associated with an activation modulation in distinct prefrontal-striatal brain regions, but not in the hippocampus. These data indicate that hippocampal and prefrontal-striatal brain regions differentially contribute to instance-based and rule-based learning.