Sex differences in regional hypothalamic volume and resting-state connectivity patterns: An ultra-high field functional magnetic resonance imaging investigation

The hypothalamus is a key homeostatic regulatory region which contains nuclei and subregions known to mediate a range of body functions. Numerous studies have revealed that the hypothalamus is critical in coordinating sexual dimorphism in neuroendocrine and behavioural phenotypes and displays sex-related structural differences. The hypothalamus is critical for the body's stress response and cortisol release, and females are twice as likely as males to develop many diseases related to hypothalamic-pituitary-adrenal axis dysfunction. Given this, it is important to understand the role sex plays in hypothalamic structure and function. In this study, we used ultra-high field functional magnetic resonance imaging to determine sex-related differences in regional hypothalamic resting state connectivity in 217 control participants: 123 females, 94 males. We found robust sex-related difference in the anatomy and function of the left supraoptic and anterior hypothalamic regions. Both hypothalamic regions displayed greater regional volumes in males compared with females. In addition, both regions displayed negative connectivity strengths in females and positive connectivity strengths in males with numerous brain regions, most significantly with association cortical areas such as the dorsolateral and medial prefrontal and cingulate cortices. These results reveal that discrete regions of the hypothalamus display sex-related differences in structure and function, as assessed by resting functional connectivity differences with various brain regions. These differences are critical for our understanding of the role of the hypothalamus in fundamental physiological processes and may underpin sex-specific vulnerabilities to neurological and psychiatric disorders.