Speaker
Description
Introduction
The hypothalamus is crucial for maintaining homeostasis, regulating sleep-wake cycles, appetite, circadian rhythm, and thermal regulation (Nieuwenhuys et al., 2008). Despite its importance the structural organization, precise boundaries, and functional differentiation of its nuclei remain incompletely 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, we aimed to develop probabilistic cytoarchitectonic maps to address intersubject variability and provide a high-resolution 3D reference map for informing studies in the living human brain.
Methods
We delineated the hypothalamus and its nuclei on every 15th cell-body stained brain sections in 10 brains (5 female) including BigBrain (Amunts et al., 2013). For creation the high-resolution BigBrain model we used a deep-learning based tool (Schiffer et al., 2021) that delineated the remaining sections. Other 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, 2024) and object instance segmentation (Upschulte et al., 2021), were applied to analyse subdivisions in more detail.
Results
We generated high-resolution 3D map of 23 nuclei of the human hypothalamus (Figure 1), that show their shapes and neighbourhood relationships with high precision. These nuclei were categorized into four rostro-caudal zones:
Preoptic zone includes the anterior periventricular and median preoptic nuclei lining the third ventricle, with the uncinate and intermediate nuclei forming a cluster around the medial preoptic nucleus.
Anterior zone contains the paraventricular nucleus with dark magnocellular neurons ventrolaterally and less intense parvocellular neurons medially, the supraoptic nucleus with densely packed magnocellular neurons, and the retrochiasmatic, suprachiasmatic and periventricular nuclei.
Tuberal zone features the ventromedial nucleus with high peripheral cell density, the smaller posteromedial nucleus between the ventromedial nucleus and mammillary body, the dorsomedial nucleus with densely packed small neurons at its centre, and the arcuate nucleus within the tuber cinerium.
Mammillary zone includes the medial and lateral mammillary nuclei. The tuberomammillary and supramammillary nuclei contain large dark magnocellular neurons, and the lateral tuberal nucleus housing medium-sized neurons in the basolateral mammillary zone.
The mean hypothalamic volume was 1492 ± 264 mm³. The Lateral (514 ± 49 mm³) and Posterior hypothalamic areas (262 ± 33 mm³) showed the highest volumes, whereas the uncinate and lateral mammillary nuclei exhibited the lowest values (0.845 ± 0.15 mm³; 1.8 ± 0.3 mm³). Permutation tests found no significant effects of hemisphere, sex, or their interaction on the shrinkage-corrected volumes for each nucleus. Intersubject variability was reflected in the probabilistic maps that will be part of the Julich-Brain Atlas (Amunts, 2020) and available via EBRAINS and other platforms.
Conclusions
In sum, we provide a detailed microstructural map of the hypothalamus, serving as a profound anatomical basis for interpreting and comparing neuroimaging data helping to refine the functional organization of the hypothalamus.
