Comparing and Contrasting the Cognitive Effects of Hippocampal and Ventromedial Prefrontal Cortex Damage: A Review of Human Lesion Studies

•The vmPFC and hippocampus are closely connected brain regions whose functions are still debated.•Here we directly compared the cognitive changes in humans with either bilateral hippocampal or bilateral vmPFC damage.•Hippocampal and vmPFC damage both affect classic ‘hippocampal’ tasks such as autobiographical memory recall.•Hippocampal and vmPFC damage have opposite effects on classic ‘vmPFC’ tasks such as moral decision making.•We propose a hierarchical network model where vmPFC initiates mental imagery including hippocampal scene construction. The hippocampus and ventromedial prefrontal cortex (vmPFC) are closely connected brain regions whose functions are still debated. In order to offer a fresh perspective on understanding the contributions of these two brain regions to cognition, in this review we considered cognitive tasks that usually elicit deficits in hippocampal-damaged patients (e.g., autobiographical memory retrieval), and examined the performance of vmPFC-lesioned patients on these tasks. We then took cognitive tasks where performance is typically compromised following vmPFC damage (e.g., decision making), and looked at how these are affected by hippocampal lesions. Three salient motifs emerged. First, there are surprising gaps in our knowledge about how hippocampal and vmPFC patients perform on tasks typically associated with the other group. Second, while hippocampal or vmPFC damage seems to adversely affect performance on so-called hippocampal tasks, the performance of hippocampal and vmPFC patients clearly diverges on classic vmPFC tasks. Third, although performance appears analogous on hippocampal tasks, on closer inspection, there are significant disparities between hippocampal and vmPFC patients. Based on these findings, we suggest a tentative hierarchical model to explain the functions of the hippocampus and vmPFC. We propose that the vmPFC initiates the construction of mental scenes by coordinating the curation of relevant elements from neocortical areas, which are then funneled into the hippocampus to build a scene. The vmPFC then engages in iterative re-initiation via feedback loops with neocortex and hippocampus to facilitate the flow and integration of the multiple scenes that comprise the coherent unfolding of an extended mental event.