Differential contributions of the primate ventrolateral prefrontal and orbitofrontal cortex to serial reversal learning.

The discrimination reversal paradigm is commonly used to measure a subject's ability to adapt their behavior according to changes in stimulus-reward contingencies. Human functional neuroimaging studies have demonstrated activations in the lateral orbitofrontal cortex (OFC) and the inferior frontal gyrus (IFG) in subjects performing this task. Excitotoxic lesions of analogous regions in marmosets have revealed, however, that although the OFC is indeed critical for reversal learning, ventrolateral prefrontal cortex (VLPFC) (analogous to IFG) is not, contributing instead to higher order processing, such as that required in attentional set-shifting and strategy transfer. One major difference between the marmoset and human studies has been the level of training subjects received in reversal learning, being far greater in the latter. Since exposure to repeated contingency changes, as occurs in serial reversal learning, is likely to trigger the development of higher order, rule-based strategies, we hypothesized a critical role of the marmoset VLPFC in performance of a serial reversal learning paradigm. After extensive training in reversal learning, marmosets received an excitotoxic lesion of the VLPFC, OFC, or a sham control procedure. In agreement with our prediction, postsurgery, VLPFC lesioned animals were impaired in performing a series of discrimination reversals, but only when novel visual stimuli were introduced. In contrast, OFC lesioned animals were impaired regardless of whether the visual stimuli were the same or different from those used during presurgery training. Together, these data demonstrate the heterogeneous but interrelated involvement of primate OFC and VLPFC in the performance of serial reversal learning.