Volumetric parcellation methodology of the human hypothalamus in neuroimaging: Normative data and sex differences

Abstract

There is increasing evidence regarding the importance of the hypothalamus for understanding sex differences in relation to neurological, psychiatric, endocrine and sleep disorders. Although different in histology, physiology, connections and function, multiple hypothalamic nuclei subserve non-voluntary functions and are nodal points for the purpose of maintaining homeostasis of the organism. Thus, given the critical importance of hypothalamic nuclei and their key multiple roles in regulating basic functions, it is important to develop the ability to conduct in vivo human studies of anatomic structure, volume, connectivity, and function of hypothalamic regions represented at the level of its nuclei. The goals of the present study were to develop a novel method of semi-automated volumetric parcellation for the human hypothalamus that could be used to investigate clinical conditions using MRI and to demonstrate its applicability. The proposed new method subdivides the hypothalamus into five parcels based on visible anatomic landmarks associated with specific nuclear groupings and was confirmed using two ex vivo hypothalami that were imaged in a 7 Tesla (7T) scanner and processed histologically. Imaging results were compared with histology from the same brain. Further, the method was applied to 44 healthy adults (26 men; 18 women, comparable on age, handedness, ethnicity, SES) to derive normative volumes and assess sex differences in hypothalamic regions using 1.5 Tesla MRI. Men compared to women had a significantly larger total hypothalamus, relative to cerebrum size, similar for both hemispheres, a difference that was primarily driven by the tuberal region, with the sex effect size being largest in the superior tuberal region and, to a lesser extent, inferior tuberal region. Given the critical role of hypothalamic nuclei in multiple chronic diseases and the importance of sex differences, we argue that the use of the novel methodology presented here will allow for critical investigations of these disorders and further delineation of potential treatments, particularly sex-specific approaches to gene and drug discoveries that involve hypothalamic nuclei.

The neural basis of sex differences in sexual behavior: A quantitative meta-analysis

“…Taken together, it may be inferred that the hypothalamus acts more autonomously and dissociatedly from other sexual processing-regions during visual sexual stimulation in women than in men. Such sex-specific hypothalamic autarchy may rest upon sex differences in the morphology and connectivity of this structure (Byne, 1998; Hines, 2010; Ibanez et al, 2001; Kilpatrick et al, 2006; Lenz and McCarthy, 2010; Makris et al, 2013; Pérez et al, 1990; Sá and Madeira, 2005; Wang et al, 2014). Furthermore, given its neuroanatomical specificity relating to sexual orientation and functional relevance for encoding sexual preferences (Balthazart, 2016; Bao and Swaab, 2011; LeVay, 2011; Poeppl et al, 2016), the sex differences in hypothalamus activation during sexual stimulation might well be represent the neural correlate of behavioral findings pointing to a less distinct sexual orientation in women (Bailey, 2009).…”

Hypothalamic atrophy is related to body mass index and age at onset in amyotrophic lateral sclerosis

“…Example of the delineation of the hypothalamus in one representative healthy subject (female, 58 years) based on 1.5 T high-resolution magnetisation-prepared gradient echo image (MPRAGE) data (voxel size: 1.0×1.2×1.0 mm 3 ). The delineation technique was optimised from Gabery et al 26 with respect to the lateral boundary definition 31. (A) Coronal slice (resampled slice thickness of 0.5 mm) through the most anterior part of the hypothalamus from the left hemispheric part (resampled in-plane resolution 62.5×62.5 µm 2 ).…”

17β-Estradiol Differentially Regulates Stress Circuitry Activity in Healthy and Depressed Women

“…In all, 180 functional volumes were acquired using a spin echo, T2 Makris et al, 2013) and implemented as overlays on the SPM8 canonical brain using the Wake Forest University PickAtlas ROI toolbox for SPM (Maldjian et al, 2003). Given hypotheses about specific brain regions, we used the small volume correction approach in SPM8, which limits voxelwise analyses to voxels within a priori ROIs.…”