Functional connectivity of the medial temporal lobe relates to learning and awareness

Learning with awareness is believed to require the involvement of the medial temporal lobe (MTL). In this study, the hypothesis tested was that this involvement is best appreciated by the pattern of MTL functional connectivity with other brain areas. In a sensory learning paradigm, human subjects were classified as AWARE or UNAWARE, on the basis of whether they noted that one of two tones predicted a visual event. Only AWARE subjects acquired and reversed a differential response to the tones. However, learned facilitation was evident in both groups. MTL activity, indexed by blood flow changes measured with positron emission tomography, was correlated with facilitation in both groups but in opposite directions (greater MTL activity was related to less facilitation in AWARE subjects but more facilitation in UNAWARE subjects). Discrimination and reversal in AWARE subjects involved anterior medial, inferior prefrontal, and lateral occipital cortices. Furthermore, unique regional patterns of MTL functional connectivity were observed: AWARE subjects engaged dorsolateral prefrontal and lateral occipital cortices, whereas UNAWARE subjects showed a more spatially restricted network involving contralateral MTL regions and the thalamus. In the AWARE group, the MTL functional connectivity pattern overlapped with regions associated with facilitation and discrimination, but in UNAWARE subjects, the MTL pattern was related only to facilitation. These results suggest that the MTL and functional connected regions, including dorsolateral and medial prefrontal cortex, acted to link facilitation and discrimination patterns in AWARE subjects. Thus, the contribution of the MTL to learning and awareness is shaped by the pattern of interregional interactions, the neural context.