Prefrontal – hippocampal pathways underlying inhibitory control over 5 memory

29 A key function of the prefrontal cortex is to support inhibitory control over behavior. It is widely believed 30 that this function extends to stopping cognitive processes as well. Consistent with this, mounting evi31 dence establishes the role of the right lateral prefrontal cortex in a clear case of cognitive control: retrie32 val suppression. Retrieval suppression refers to the ability to intentionally stop the retrieval process that 33 arises when a reminder to a memory appears. Functional imaging data indicates that retrieval suppres34 sion involves top-down modulation of hippocampal activity by the dorsolateral prefrontal cortex, but the 35 anatomical pathways supporting this inhibitory modulation remain unclear. Here we bridge this gap by 36 integrating key findings about retrieval suppression observed through functional imaging with a detailed 37 consideration of relevant anatomical pathways observed in non-human primates. Focusing selectively on 38 the potential role of the anterior cingulate cortex, we develop two hypotheses about the pathways medi39 ating interactions between lateral prefrontal cortex and the medial temporal lobes during suppression, 40 and their cellular targets: the entorhinal gating hypothesis, and thalamo-hippocampal modulation via 41 the nucleus reuniens. We hypothesize that whereas entorhinal gating is well situated to stop retrieval 42 proactively, thalamo-hippocampal modulation may interrupt an ongoing act of retrieval reactively. 43 Isolating the pathways that underlie retrieval suppression holds the potential to advance our understand44 ing of a range of psychiatric disorders characterized by persistent intrusive thoughts. More broadly, an 45 anatomical account of retrieval suppression would provide a key model system for understanding inhi46 bitory control over cognition. 47 ! 2015 Published by Elsevier Inc. 48