Regional hypothalamic resting state connectivity with limbic structures: An ultra-high field functional magnetic resonance imaging investigation

The hypothalamus contains discrete nuclei, each with distinct functions. Although human studies have investigated hypothalamo-cortical interactions in disease states, due to spatial resolution limitations, these studies were not able to explore interactions of specific hypothalamic subnuclei. Here, we used ultra-high field (7-Tesla) functional magnetic resonance imaging to explore resting connectivity patterns in six discrete hypothalamic regions in awake humans (n = 150). We found that the lateral, posterior, and paraventricular hypothalamus demonstrated widespread connectivity to all prefrontal subregions (dorsolateral prefrontal [dlPFC], inferior frontal, orbital and polar frontal [OPF], medial prefrontal [mPFC], cingulate cortices) as well as the insula, and that it was the lateral hypothalamus which displayed the most widespread connectivity. The anterior hypothalamus demonstrated connectivity with the dlPFC, OPF, mPFC and insula, while the dorsomedial hypothalamus showed connectivity to the dlPFC, OPF, mPFC, and insula. In contrast, the ventromedial hypothalamus showed no significant connectivity to either prefrontal or insula regions. All hypothalamic regions showed connectivity with the bed nucleus of the stria terminalis, and all except for the anterior nucleus showed connectivity with numerous amygdala subregions. The ventromedial and, to a lesser extent, the posterior hypothalamus showed connectivity with the medial dorsal, ventral anterior, and ventrolateral thalamus. This study shows that the hypothalamus, the PFC, the insula, and associated limbic areas strongly interact, but these interactions are not equal throughout both the hypothalamus and associated regions. These findings are broadly consistent with preclinical neuroanatomical tract tracing data, but they provide new insights into potential differences in connectivity patterns in humans.