Ventrolateral prefrontal cortex activity associated with individual differences in arbitrary delayed...

To describe the neural substrates of successful episodic long-term memory encoding, we collected functional magnetic-resonance imaging data as participants completed an arbitrary delayed auditory paired-association learning task. During the task, subjects learned predefined but hidden stimulus pairs by trial and error based on visual feedback. Delay period activity represents the retrieval of the relationship between the cue item and its candidate for associates, that is, working memory. Our hypothesis was that the neural substrates of working memory would be related to long-term memory encoding in a performance-dependent manner. Thus, inter-individual variance in performance following a fixed learning set would be associated with differing neural activations during the delay period. The number of learning trials was adjusted such that performance following completion of the learning set varied across subjects. Each trial consisted of the successive presentation of two stimuli (first stimulus and second stimulus [S2]) with a fixed delay interval, allowing extraction of sustained activity during the delay period. Sustained activities during the delay period were found in the bilateral dorsolateral prefrontal cortex, intraparietal sulcus, and left ventrolateral prefrontal cortex, as well as the premotor and pre-supplementary motor areas. The activities did not change in strength across learning, suggesting that these effects represent working memory components. The sustained activity in the ventrolateral prefrontal region was correlated with task performance. Task performance was also positively correlated with the decrement in S2/feedback-related activity during learning in the superior temporal sulcus, a region previously shown to be involved in association learning. These findings are consistent with lesion and neuroimaging studies showing that the ventrolateral prefrontal cortex plays an important role in long-term memory encoding, and raise the possibility that working memory processes interact with long-term memory formation as represented by the covariation of activity in the superior temporal sulcus and the ventrolateral prefrontal cortex.