The hippocampus displays a complex organization and function that is perturbed in many neuropathologies. Histological work revealed a complex arrangement of subfields along the medial–lateral and the ventral–dorsal dimension, which contrasts with the anterior–posterior functional differentiation. The variety of maps has raised the need for an integrative multimodal view. We applied connectivity-based parcellation to 1) intrinsic connectivity 2) task-based connectivity, and 3) structural covariance, as complementary windows into structural and functional differentiation of the hippocampus. Strikingly, while functional properties (i.e., intrinsic and task-based) revealed similar partitions dominated by an anterior–posterior organization, structural covariance exhibited a hybrid pattern reflecting both functional and cytoarchitectonic subdivision. Capitalizing on the consistency of functional parcellations, we defined robust functional maps at different levels of partitions, which are openly available for the scientific community. Our functional maps demonstrated a head–body and tail partition, subdivided along the anterior–posterior and medial–lateral axis. Behavioral profiling of these fine partitions based on activation data indicated an emotion–cognition gradient along the anterior–posterior axis and additionally suggested a self-world-centric gradient supporting the role of the hippocampus in the construction of abstract representations for spatial navigation and episodic memory.

Previous whole-brain functional connectivity studies achieved successful classifications of patients and healthy controls but only offered limited specificity as to affected brain systems. Here, we examined whether the connectivity patterns of functional systems affected in schizophrenia (SCZ), Parkinson’s disease (PD), or normal aging equally translate into high classification accuracies for these conditions. We compared classification performance between pre-defined networks for each group and, for any given network, between groups. Separate support vector machine classifications of 86 SCZ patients, 80 PD patients, and 95 older adults relative to their matched healthy/young controls, respectively, were performed on functional connectivity in 12 task-based, meta-analytically defined networks using 25 replications of a nested 10-fold cross-validation scheme. Classification performance of the various networks clearly differed between conditions, as those networks that best classified one disease were usually non-informative for the other. For SCZ, but not PD, emotion-processing, empathy, and cognitive action-control networks distinguished patients most accurately from controls. For PD, but not SCZ, networks subserving autobiographical or semantic memory, motor execution, and theory-of-mind cognition yielded the best classifications. In contrast, young–old classification was excellent based on all networks and outperformed both clinical classifications. Our pattern-classification approach captured associations between clinical and developmental conditions and functional network integrity with a higher level of specificity than did previous whole-brain analyses. Taken together, our results support resting-state connectivity as a marker of functional dysregulation in specific networks known to be affected by SCZ and PD, while suggesting that aging affects network integrity in a more global way.

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The hippocampus is a plastic region and highly susceptible to ageing and dementia. Previous studies explicitly imposed a priori models of hippocampus when investigating ageing and dementia-specific atrophy but led to inconsistent results. Consequently, the basic question of whether macrostructural changes follow a cytoarchitectonic or functional organization across the adult lifespan and in age-related neurodegenerative disease remained open. The aim of this cross-sectional study was to identify the spatial pattern of hippocampus differentiation based on structural covariance with a data-driven approach across structural MRI data of large cohorts (n = 2594). We examined the pattern of structural covariance of hippocampus voxels in young, middle-aged, elderly, mild cognitive impairment and dementia disease samples by applying a clustering algorithm revealing differentiation in structural covariance within the hippocampus. In all the healthy and in the mild cognitive impaired participants, the hippocampus was robustly divided into anterior, lateral and medial subregions reminiscent of cytoarchitectonic division. In contrast, in dementia patients, the pattern of subdivision was closer to known functional differentiation into an anterior, body and tail subregions. These results not only contribute to a better understanding of co-plasticity and co-atrophy in the hippocampus across the lifespan and in dementia, but also provide robust data-driven spatial representations (i.e. maps) for structural studies.