PT - JOURNAL ARTICLE AU - Marshall A. Dalton AU - Peter Zeidman AU - Cornelia McCormick AU - Eleanor A. Maguire TI - Differentiable processing of objects, associations and scenes within the hippocampus AID - 10.1101/208827 DP - 2018 Jan 01 TA - bioRxiv PG - 208827 4099 - http://biorxiv.org/content/early/2018/06/11/208827.short 4100 - http://biorxiv.org/content/early/2018/06/11/208827.full AB - The hippocampus is known to be important for a range of cognitive functions including episodic memory, spatial navigation and future-thinking. Wide agreement on the exact nature of its contribution has proved elusive, with some theories emphasising associative processes and another proposing that scene construction is its primary role. To directly compare these accounts of hippocampal function in human males and females, we devised a novel mental imagery paradigm where different tasks were closely matched for associative processing and mental construction, but either did or did not evoke scene representations, and we combined this with high resolution functional MRI. The results were striking in showing that differentiable parts of the hippocampus, along with distinct cortical regions, were recruited for scene construction or non-scene-evoking associative processing. The contrasting patterns of neural engagement could not be accounted for by differences in eye movements, mnemonic processing or the phenomenology of mental imagery. These results inform conceptual debates in the field by showing that the hippocampus does not seem to favour one type of process over another; it is not a story of exclusivity. Rather, there may be different circuits within the hippocampus, each associated with different cortical inputs, which become engaged depending on the nature of the stimuli and the task at hand. Overall, our findings emphasise the importance of considering the hippocampus as a heterogeneous structure, and that a focus on characterising how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition.Significance statement The hippocampus is known to be important for a range of cognitive functions including episodic memory, spatial navigation and future-thinking. Wide agreement on the exact nature of its contribution has proved elusive. Here we used a novel mental imagery paradigm and high resolution fMRI to compare accounts of hippocampal function that emphasise associative processes with a theory that proposes scene construction as a primary role. The results were striking in showing that differentiable parts of the hippocampus, along with distinct cortical regions, were recruited for scene construction or non-scene-evoking associative processing. We conclude that a greater emphasis on characterising how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition.This work was supported by a Wellcome Principal Research Fellowship to E.A.M. (101759/Z/13/Z) and the Centre by a Centre Award from Wellcome (203147/Z/16/Z). The authors are grateful to David Bradbury for technical assistance.AbbreviationsENTEntorhinal cortexEVCEarly visual corticesPCCPosterior cingulate cortexPHCPosterior parahippocampal cortexPRCPerirhinal cortexRSCRetrosplenial cortex