Graph analysis of the anatomical network organization of the hippocampal formation and parahippocampal region in the rat.

Graph theory was used to analyze the anatomical network of the rat hippocampal formation and the parahippocampal region (van Strien et al., Nat Rev Neurosci 10(4):272-282, 2009). For this analysis, the full network was decomposed along the three anatomical axes, resulting in three networks that describe the connectivity within the rostrocaudal, dorsoventral and laminar dimensions. The rostrocaudal network had a connection density of 12% and a path length of 2.4. The dorsoventral network had a high cluster coefficient (0.53), a relatively high path length (1.62) and a rich club was identified. The modularity analysis revealed three modules in the dorsoventral network. The laminar network contained most information. The laminar dimension revealed a network with high clustering coefficient (0.47), a relatively high path length (2.11) and four significantly increased characteristic network building blocks (structural motifs). Thirteen rich club nodes were identified, almost all of them situated in the parahippocampal region. Six connector hubs were detected and all of them were located in the entorhinal cortex. Three large modules were revealed, indicating a close relationship between the perirhinal and postrhinal cortex as well as between the lateral and medial entorhinal cortex. These results confirmed the central position of the entorhinal cortex in the (para)hippocampal network and this possibly explains why pathology in this region has such profound impact on cognitive function, as seen in several brain diseases. The results also have implications for the idea of strict separation of the "spatial" and the "non-spatial" information stream into the hippocampus. This two-stream memory model suggests that the information influx from, respectively, the postrhinal-medial entorhinal cortex and the perirhinal-lateral entorhinal cortex is separate, but the current analysis shows that this apparent separation is not determined by anatomical constraints.