Identification of the human sympathetic connectome involved in blood pressure regulation

Abstract

We review our recent data obtained on the cortical and subcortical components of the human sympathetic connectome - the network of regions involved in the sympathetic control of blood pressure. Specifically, we functionally identified the human homologue of the rostral ventrolateral medulla (RVLM), the primary premotor sympathetic nucleus in the medulla responsible for generating sympathetic vasoconstrictor drive. By performing functional magnetic resonance imaging (fMRI) of the brain at the same time as recording muscle sympathetic nerve activity (MSNA), via a microlectrode inserted into the common peroneal nerve, we are able to identify areas of the brain involved in the generation of sympathetic outflow to the muscle vascular bed, a major contributor to blood pressure regulation. Together with functional connectivity analysis of areas identified through MSNA-coupled fMRI, we have established key components of the human sympathetic connectome and their roles in the control of blood pressure. Whilst our studies confirm the role of lower brainstem regions such as the NTS, CVLM and RVLM in baroreflex control of MSNA, our findings indicate that the insula – hypothalamus – PAG – RVLM circuitry is tightly coupled to MSNA at rest. This fits with data obtained from experimental animals, but also emphasizes the role of areas above the brainstem in the regulation of blood pressure.