Prefrontal and medial temporal lobe interactions in long-term memory

Key Points Much progress has been made by cognitive neuroscientists in understanding the separate roles of the medial temporal and prefrontal lobes in memory, but the way in which these regions interact in the processes of remembering has been neglected. This review provides a synthesis of evidence from human and animal neuropsychology, functional neuroimaging, neurophysiology and computational modelling, through which the functional interactions between prefrontal and medial temporal cortices can be better understood. Since the first reports of patients with amnesia, evidence has converged on a role for the medial temporal lobes in the encoding, storage and retrieval of long-term memories. Controversies include whether there is differential involvement of regions such as the hippocampus and perirhinal cortex in processes of recollection and familiarity, and the long-term role of these regions in consolidation of memories from the past. The prefrontal cortex is considered to support processes of cognitive control that are important for memory function. Accordingly, frontal lobe damage is often associated with particular memory impairments. Regional distinctions are evident within the frontal lobes, with left/right lateralization on the basis of material type and medial/lateral differentiation between reward-based mapping and goal-directed mnemonic control, respectively. Within lateral prefrontal cortex, there is a further distinction between ventral (specification and maintenance) and dorsal (monitoring and manipulation) regions. Recent advances in primate crossed-lesion neuropsychology, human functional effective connectivity, single-cell electrophysiology and computational modelling highlight the importance of interactions between prefrontal cortex and medial temporal lobe in remembering. These new insights indicate that an understanding of these interactions will be crucial if we are to move closer to a full account of how memory is supported in the brain. At encoding, information is processed by a hierarchy of unimodal and polymodal cortical areas, resulting in a bound representation of associated features in the medial temporal lobe. Through interactions with different regions of prefrontal cortex, top-down control of the encoding process is provided, modifying, elaborating and organizing medial temporal lobe representations in a goal-dependent manner, and ensuring that they are sufficiently discrete to be amenable for long-term storage. During retrie