Hippocampal connectivity patterns echo macroscale cortical evolution in the primate brain

Abstract

The hippocampus is involved in numerous cognitive functions, some of which have uniquely human aspects, such as autobiographical memory. Hippocampal anatomy, however, is typically considered conserved across primates and its evolutionary diversification is rarely studied. Comparing hippocampal structure and function is, therefore, critical for understanding human brain architecture. Here, we developed a novel comparative framework to study the hippocampus across species characterising its geometry, microstructure, and functional network embedding. In humans and macaques, we generated a new comparative space that represents the hippocampus as an unfolded surface, which respects its sheet-like anatomy. We mapped histological and MRI-derived markers of microstructure to the hippocampal surface and integrated it with low-dimensional embedding of resting-state MRI connectivity data. Our results demonstrate that the micro– and macro-structural organisation of the hippocampus are overall conserved in both species, showing consistent anterior-posterior and subfield-to-subfield differentiation. Furthermore, while hippocampal functional organisation also follows anterior-posterior trends in both species, hippocampal functional connectivity markedly reflected evolutionary reconfiguration of transmodal networks, in particular the default-mode network. Specifically, the inferior parietal lobe in the macaque mirrors an incomplete integration of the default mode network in non-human primates. By combining fine-grained anatomical investigation with large-scale functional imaging, we showed that microstructurally preserved regions like the hippocampus may still undergo functional reconfiguration, due to their embedding in higher-order association networks.SummaryWhile the hippocampus is key for uniquely human cognitive abilities, it is also a phylogenetically old cortex and paradoxically considered evolutionarily preserved. Here, we introduce a comparative framework to quantify preservation and reconfiguration of hippocampal organisation in primate evolution, by analysing the hippocampus as an unfolded cortical surface that is geometrically matched across species. Our findings revealed an overall conservation of hippocampal macro– and micro-structure, showing anterior-posterior and, perpendicularly, subfield-related organisational axes in both humans and macaques. However, while functional organisation in both species also followed an anterior-posterior axis, the latter showed a marked evolutionary reconfiguration, which mirrors a rudimentary integration of the default-mode-network in non-human primates. Our findings suggest that microstructurally preserved regions like the hippocampus may still undergo functional reconfiguration in primate evolution, due to their embedding in heteromodal association networks.

HippoMaps: Multiscale Cartography of Human Hippocampal Organization

“…It broad involvement in multiple macroscale networks is clearly compatible with the key role the hippocampus plays in numerous cognitive and affective processes, including memory and language function, together with affective reactivity, stress as well as spatial navigation (Barnett et al, 2024;O'Keefe & Nadel, 1978;Stachenfeld et al, 2014Stachenfeld et al, , 2017Whittington et al, 2022). Notably, the hippocampus is also recognized as one of the proximate evolutionary origins of the neocortex (Puelles et al, 2019;Sanides, 1969), making it a candidate structure to investigate principles of evolutionary conservation and innovation in the primate lineage (Eichert et al, 2023). Collectively, these insights contribute to the notion that the hippocampus is a microcosm of the brain, and that an assessment of its sub-regional organization provides key insights into human neural architectures.…”

HippoMaps: Multiscale cartography of the human hippocampal formation

“…This has begun a new wave of high-sensitivity hippocampally-focused studies in topics including the mapping of histology features (J. DeKraker et al, 2020; Paquola, Benkarim, et al, 2020), blood perfusion (Haast et al ., 2023; Ngo et al ., 2023), biophysically-constrained diffusion (Karat et al ., 2023), hippocampal sclerosis (Ripart et al ., 2023), neurodevelopmental trajectories (Hanson et al ., 2023), functional connectivity (Cabalo et al ., 2023; Lariviere et al ., 2023; Xie et al ., 2023), visual receptive field mapping (Leferink et al ., 2023), and cross-species comparison (Eichert et al ., 2023). With the increasing aggregation of hippocampal features in a common reference space, it is now possible to devise repositories that allow for a broad contextualization of hippocampal findings.…”

“…It broad involvement in multiple macroscale networks is clearly compatible with the key role the hippocampus plays in numerous cognitive and affective processes, including memory and language function, together with affective reactivity, stress as well as spatial navigation (Barnett et al, 2024; O’Keefe & Nadel, 1978; Stachenfeld et al, 2014, 2017; Whittington et al, 2022). Notably, the hippocampus is also recognized as one of the proximate evolutionary origins of the neocortex (Puelles et al, 2019; Sanides, 1969), making it a candidate structure to investigate principles of evolutionary conservation and innovation in the primate lineage (Eichert et al ., 2023). Collectively, these insights contribute to the notion that the hippocampus is a microcosm of the brain, and that an assessment of its sub-regional organization provides key insights into human neural architectures.…”

“…Similar to neocortical surface extraction and registration procedures (Boucher et al, 2009;Dale et al, 1999;Fischl, Sereno, Tootell, et al, 1999;Kim et al, 2005;Lyttelton et al, 2007;MacDonald et al, 2000), this allows for topology-informed inter-subject registration to a standardized unfolded space (Jordan DeKraker et al, 2023). This has begun a new wave of high-sensitivity hippocampally-focused studies in topics including the mapping of histology features , blood perfusion (Haast et al, 2023;Ngo et al, 2023), biophysically-constrained diffusion (Karat et al, 2023), hippocampal sclerosis (Ripart et al, 2023), neurodevelopmental trajectories (Hanson et al, 2023), functional connectivity (Cabalo et al, 2023;Lariviere et al, 2023;Xie et al, 2023), visual receptive field mapping (Leferink et al, 2023), and crossspecies comparison (Eichert et al, 2023). With the increasing aggregation of hippocampal features in a common reference space, it is now possible to devise repositories that allow for a broad contextualization of hippocampal findings.…”