Multimodal Mapping of the Hippocampus across the lifespan and in dementia

The hippocampus is associated with behaviors such as memory and navigation, and is one ofthe first brain regions to be affected in diseases such as Alzheimer's dementia, depression andanxiety disorders. Patients who have undergone hippocampal resection experience greatdifficulties in everyday life and suffer from anterograde and retrograde amnesia.Understanding how the hippocampus is organized and what behaviors are associated with it,is therefore of utmost importance. The mapping of the hippocampus, i.e. the description of itsorganization, has so far been limited to the cellular level. However, a description of theorganization of the hippocampus at the level of large-scale networks is missing, which may bemore important for drawing conclusions about behavior than the cellular organization.With the use of imaging techniques and the method of "Connectivity-Based Parcellation", it ispossible to create in-vivo maps of the hippocampus across a large number of participants. Themethod of Connectivity-Based Parcellation divides the hippocampus into subregions thatdiffer particularly strongly in their connectivity profiles and display therefore a specificdifferentiation pattern. The present work thus aimed at mapping the hippocampus on the basisof functional connectivity and structural covariance. Functional connectivity was eithercalculated meta-analytically across tasks of published functional studies or measured underresting state conditions with the magnetic resonance tomography. Structural covariance is arelatively new measure that estimates the co-variation in grey matter intensities acrossindividuals and thus maps co-plasticity and co-atrophy as brain regions grow or degeneratetogether.In addition to mapping the hippocampus, I was also strongly interested in investigatingwhether differentiation patterns within the hippocampus change over the course of life and indementia and whether they can be distinguished from each other. Therefore changes inhippocampal organization based on alterations in structural covariance networks were studied.The investigations were carried out on hundreds of functional and structural imaging datafrom open accessible databases. In contrast to the cytoarchitectonic organization, theorganization of the hippocampus based on functional connectivity showed a differentiationalong the anterior-posterior axis with a subdivision into an anterior, middle and posteriorsubregion. In contrast, the organization based on structural covariance showed a mediallateraldifferentiation into an anterior, medial and lateral subregion similar to thedifferentiation into cornu ammonis and subiculum.8Age-related changes were mainly found in the posterior region of the hippocampus, where thelateral subregion decreased. However, the hippocampal differentiation pattern in dementiaclosely resembled a functional division along the anterior-posterior axis, as the lateralsubregion extended strongly in the medial direction and covered almost the entirehippocampal body. These changes were interpreted as a possible indication that in dementiafunctional networks are particularly affected by the spread of pathogens such asneurofibrillary tangles and amyloid beta plaques and have therefore a long-term effect on theco-atrophy of the hippocampus.To understand in which behaviors the hippocampus is involved, I characterized both thesubregions and the associated networks behaviorally using databases that archive thousandsof activation studies. The results suggested that the anterior hippocampus is more involved inself-centric information processing and the posterior hippocampus more involved in worldcentericinformation processing. In addition, it can be assumed that based on the networks ofstructural covariance, the medial subregion has something to do with visual-motor processing.The present work therefore showed that the hippocampus has both an anterior-posterior and amedial-lateral organization, depending on the type of networks, whether functional orstructural. Structural networks are not stable over the lifespan but change with age anddementia mirroring different underlying processes

Jobverteilung im Gehirn

Seit Jahrhunderten erforschen Neurowissenschaftler die Rolle einzelner Hirnareale. Dank großer Datenbanken erstellen sie heute erstaunlich detaillierte funktionelle Karten, etwa des Hippocampus

Characterizing the gradients of structural covariance in the human hippocampus.

The hippocampus is a plastic brain structure that has been associated with a range of behavioral aspects but also shows vulnerability to the most frequent neurocognitive diseases. Different aspects of its organization have been revealed by studies probing its different neurobiological properties. In particular, histological work has shown a pattern of differentiation along the proximal-distal dimension, while studies examining functional properties and large-scale functional integration have primarily highlighted a pattern of differentiation along the anterior posterior dimension. To better understand how these organizational dimensions underlie the pattern of structural covariance (SC) in the human hippocampus, we here applied a non-linear decomposition approach, disentangling the major modes of variation, to the pattern of grey matter volume correlation of hippocampus voxels with the rest of the brain in a sample of 377 healthy young adults. We additionally investigated the consistency of the derived gradients in an independent sample of life-span adults and also examined the relationships between these major modes of variations and the patterns derived from microstructure and functional connectivity mapping. Our results showed that similar major modes of SC-variability are identified across the two independent datasets. The major dimension of variation found in SC runs along the hippocampal anterior-posterior axis and followed closely the principal dimension of functional differentiation, suggesting an influence of network level interaction in this major mode of morphological variability. The second main mode of variability in the SC showed a gradient along the dorsal-ventral axis, and was moderately related to variability in hippocampal microstructural properties. Thus our results depicting relatively reliable patterns of SC variability within the hippocampus show an interplay between the already known organizational principles on the pattern of variability in hippocampus’ macrostructural properties. This study hence provides a first insight on the underlying organizational forces generating different co-plastic modes within the human hippocampus that may, in turn, help to better understand different vulnerability patterns of this crucial structure in different neurological and psychiatric diseases