Functional Architecture of the Human Hypothalamus: Cortical Coupling and Subregional Organization Using 7-Tesla fMRI

The hypothalamus plays an important role in the regulation of the body's metabolic state and behaviors related to survival. Despite its importance however, many questions exist regarding the intrinsic and extrinsic connections of the hypothalamus in humans, especially its relationship with the cerebral cortex. As a heterogeneous structure, it is possible that the hypothalamus is composed of different subregions, which have their own distinct relationships with the cerebral cortex. Previous work on functional connectivity in the human hypothalamus have either treated it as a unitary structure or relied on methodological approaches that are limited in modeling its intrinsic functional architecture. Here, we used resting-state data from ultra-high field 7-Tesla fMRI and a data-driven analytical approach to identify functional subregions of the human hypothalamus. Our approach identified four functional hypothalamic subregions based on intrinsic functional connectivity, which in turn showed distinct patterns of functional connectivity with the cerebral cortex. Overall, all hypothalamic subregions showed stronger connectivity with a cortical network (Cortical Network 1) composed primarily of frontal, midline, and limbic cortical areas and weaker connectivity with a second cortical network composed largely of posterior sensorimotor regions (Cortical Network 2). Of the hypothalamic subregions, the anterior hypothalamus showed the strongest connection to Cortical Network 1, while a more ventral subregion containing the anterior hypothalamus extending to the tuberal region showed the weakest connectivity. The findings support the use of ultra-high field, high-resolution imaging in providing a more incisive investigation of the human hypothalamus that respects its complex internal structure and extrinsic functional architecture.