PT  - JOURNAL ARTICLE
AU  - Alexander J. Barnett
AU  - Walter Reilly
AU  - Halle Dimsdale-Zucker
AU  - Eda Mizrak
AU  - Zachariah Reagh
AU  - Charan Ranganath
TI  - Organization of cortico-hippocampal networks in the human brain
AID  - 10.1101/2020.06.09.142166
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.09.142166
4099  - http://biorxiv.org/content/early/2020/06/10/2020.06.09.142166.short
4100  - http://biorxiv.org/content/early/2020/06/10/2020.06.09.142166.full
AB  - Episodic memory is thought to depend on interactions between the hippocampus and a set of closely interconnected regions that comprise the default mode network (DMN)—a large-scale network that has been identified with resting-state fMRI. Here, using data-driven analyses of resting-state fMRI data to characterize cortico-hippocampal network connectivity, we identified a discrete set of subnetworks that interact with the hippocampus. Specifically, we found that the hippocampus closely affiliated with the DMN and with a “Medial Temporal Network” (MTN) that included regions in the medial temporal lobe and retrosplenial cortex. The DMN could be further subdivided into three subnetworks: a “Posterior Medial” Subnetwork comprised of regions in the posterior cingulate, lateral parietal, and dorsal prefrontal cortex, an “Anterior Temporal” Subnetwork comprised of regions in the temporopolar, lateral orbitofrontal, and dorsal medial prefrontal cortex, and a “Medial Prefrontal” Subnetwork comprised of regions in the ventral medial prefrontal, and entorhinal cortex. These cortico-hippocampal networks vary in their functional connectivity along the hippocampal long-axis, and analyses of an independent task-fMRI dataset revealed that the three DMN subnetworks represent different kinds of information during memory-guided decision-making. Finally, a data-driven meta-analysis of functional imaging studies of cognition suggests new hypotheses regarding the functions of the MTN and DMN subnetworks, thus providing a framework to guide future research on the neural architecture of episodic memory.Significance Statement Network neuroscience has identified large-scale networks across the human brain, but this literature focuses almost exclusively on cortical regions, with sparse characterization of subcortical regions like the hippocampus. The hippocampus is critical for encoding and retrieving episodic memories, but it is currently unclear how the hippocampus interacts with distributed networks in the brain. Here, we used network neuroscience techniques to identify and characterize cortico-hippocampal networks. We find that these cortico-hippocampal networks can be differentiated on the basis of functional connectivity along the hippocampal long-axis, information represented in an independent task-fMRI dataset, and in a meta-analysis of task fMRI studies. Our work demonstrates that the functional organization of memory processes may be determined by the network topology of the human brain.Competing Interest StatementThe authors have declared no competing interest.