Prefrontal regions supporting spontaneous and directed application of verbal learning strategies - Evidence from PET

The prefrontal cortex has been implicated in strategic memory processes, in cluding the ability to use semantic organizational strategies to facilitate episodic learning. An important feature of these strategies is the way the y are applied in novel or ambiguous situations-failure to initiate effectiv e strategies spontaneously in unstructured settings is a central cognitive deficit in patients with frontal lobe disorders. The current study examined strategic memory with PET and a verbal encoding paradigm that manipulated semantic organization in three encoding conditions: spontaneous, directed a nd unrelated. During the spontaneous condition, subjects heard 24 words tha t were related in four categories but presented in mixed order, and they we re not informed of this structure beforehand. Any semantic reorganization w as, therefore, initiated spontaneously by the subject. In the directed cond ition, subjects were given a different list of 24 related words and explici tly instructed to notice relationships and mentally group related words tog ether to improve memory. The unrelated list consisted of 24 unrelated words . Behavioural measures included semantic clustering, which assessed active regrouping of words into semantic categories during free recall. In graded PET contrasts (directed > spontaneous > unrelated), two distinct activation s were found in left inferior prefrontal cortex (inferior frontal gyrus) an d left dorsolateral prefrontal cortex (middle frontal gyrus), corresponding to levels of semantic clustering observed in the behavioural data. Additio nal covariate analyses in the first spontaneous condition indicated that bl ood how in orbitofrontal cortex (OFC) was strongly correlated with semantic clustering scores during immediate free recall. Thus, blood how in OFC dur ing encoding predicted which subjects would spontaneously initiate effectiv e strategies during free recall. Our findings indicate that OFC performs an important, and previously unappreciated, role in strategic memory by suppo rting the early mobilization of effective behavioural strategies in novel o r ambiguous situations. Once initiated, lateral regions of left prefrontal cortex control verbal semantic organization.