High-resolution 3D Mapping of the Human Hypothalamus:Towards a Comprehensive Cytoarchitectonic Atlas

2151 

Abstract Submission 

Alexey Chervonnyy¹, Christian Schiffer², Eric Upschulte², Sebastian Bludau², Hartmut Mohlberg², Katrin Amunts^1,2

¹Cécile und Oskar Vogt-Institut für Hirnforschung, Düsseldorf, Germany, ²Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany

Alexey Chervonnyy  
Cécile und Oskar Vogt-Institut für Hirnforschung
Düsseldorf, Germany

Christian Schiffer  
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich
Jülich, Germany

Eric Upschulte  
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich
Jülich, Germany

Sebastian Bludau  
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich
Jülich, Germany

Hartmut Mohlberg  
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich
Jülich, Germany

Katrin Amunts  
Cécile und Oskar Vogt-Institut für Hirnforschung|Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich
Düsseldorf, Germany|Jülich, Germany

The hypothalamus plays a central role in maintaining homeostasis and coordinating various physiological and behavioural processes including sleep-wake cycles, appetite, circadian rhythm and thermal regulation (Nieuwenhuys et.al., 2008). It encompasses distinct nuclei with a specific microstructure, connectivity, molecular organisation. Despite its importance, the structural organization and precise boundaries of the human hypothalamus, and the functional differentiation of its nuclei, are still not fully understood. Existing anatomical maps of the hypothalamus do not reflect interindividual variability in 3D space; they often lack the spatial resolution and morphological detail to provide a comprehensive understanding of this complex region and to inform neuroimaging studies about the brain's microstructure. Therefore, here we aimed to develop probabilistic cytoarchitectonic maps to address inter-subject variability and to provide a high-resolution 3D reference map for informing studies in the living human brain.

We delineated the hypothalamus and its nuclei on every 15th cell-body stained brain section in 10 brains (5 female, 5 male) including the BigBrain (Amunts et al., 2013). For creating maps in the high-resolution BigBrain model, we used a deep-learning based tool (Schiffer et al., 2021). The ten brains were used to create probability maps that capture intersubject variability in space and location of areas. To do this, brains were 3D reconstructed and superimposed in standard reference space (Amunts et. al., 2020). Quantitative tools, including texture analysis (Devakuruparan, 2022) and object instance segmentation (Upschulte et al., 2021), were applied to characterize subdivisions in more detail.

We generated high-resolution 3D maps of 20 nuclei of the human hypothalamus (Figure 1), that show their shapes and neighbourhood relationships with high precision. They were associated to four rostro-caudal zones: preoptic, anterior, tuberal, and mammillary.
In the preoptic zone, we found the periventricular and median preoptic nuclei, lining the third ventricle. The uncinate and intermediate nuclei form a compact cluster around the medial preoptic nucleus.
In the anterior hypothalamic area, we observed the paraventricular nucleus housing magnocellular neurons in its ventrolateral region and parvocellular neurons medially. Also, we identified the supraoptic nucleus with densely packed magnocellular neurons, and the suprachiasmatic and anterior periventricular nuclei.
In the tuberal region, we located the ventromedial nucleus exhibiting high peripheral cell density. Adjacent, the posteromedial nucleus, smaller in size, fills the space between the ventromedial nucleus and mammillary body. The dorsomedial nucleus holds densely packed small neurons at its center. The arcuate nucleus consists of densely packed neurons within the tuber cinerium.
In the mammillary region, we found the medial and lateral mammillary nuclei. The tuberomammillary and supramammillary nuclei contain large dark magnocellular neurons. Finally, the lateral tuberal nucleus in the basolateral mammillary zone houses three subnuclei of medium-sized neurons, positioned closer to the periphery than the nucleus center.
The mean hypothalamic volume was 1688 ± 48 mm³. The lateral (446 ± 49 mm³) and posterior hypothalamic areas (248 ± 50 mm³) showed the highest volumes, whereas the uncinate and lateral mammillary nuclei exhibited the lowest values (1.2 ± 0.3 mm³; 1.35 ± 0.2 mm³). Permutation tests found no significant effects of hemisphere, sex, or their interaction on the shrinkage-corrected volumes for each nucleus. Intersubject variability was also reflected in the probabilistic maps that will be part of the Julich-Brain Atlas (Amunts, 2020).

In sum, we provide a detailed microstructural map of the hypothalamus, serving as a comprehensive anatomical basis for interpreting and comparing neuroimaging data helping to refine the functional organization of the hypothalamus.

Subcortical Structures ¹

Brain Atlases ²

Atlasing

Modeling

Structures

Sub-Cortical

Other - Hypothalamus