"Sculpting the response space"--an account of left prefrontal activation at encoding.

Left lateral prefrontal cortex (PFC) is consistently activated in neuroimaging studies of memory encoding. Its role, however, remains unclear. We describe two functional magnetic resonance imaging (fMRI) studies addressing this question. In the first we used a blocked experimental design to explore the effect of repeated encoding of word paired associates. Initial presentation of word pairs was associated with left ventrolateral PFC activation that attenuated with subsequent presentations of the same lists. When well-learned lists were presented with word pairs rearranged, a left PFC activation, greater than that associated with the initial presentation, was observed. In a second experiment, the formation of these associative relationships was explored using an event-related design. Two types of word pairs were presented: closely related (e.g., King...Queen) and distantly related (e.g., Net...Ship). The same region of left PFC was differentially sensitive to these two event-types, showing a greater response for distantly related pairs. We suggest that left PFC activity, at memory encoding, reflects operations necessary to the formation of meaningful associations in the service of optimal learning. A crucial feature of such associative processing lies in selecting appropriate, and inhibiting inappropriate, semantic attributes of the study material.