Real-time imaging of the medullary circuitry involved in the generation of spontaneous muscle sympathetic nerve activity in awake subjects

To understand the central neural processes involved in blood pressure regulation we recorded muscle sympathetic nerve activity (MSNA) via a tungsten microelectrode in the common peroneal nerve while performing functional magnetic resonance imaging (fMRI) of the brainstem at 3T. Blood oxygen level dependent (BOLD) changes in signal intensity were measured over 4 s every 8 s (200) volumes; MSNA was recorded during the previous 4 s epoch, which takes into account peripheral conduction delays along unmyelinated axons and neurovascular coupling delays. Analysis of temporal coupling between BOLD signal intensity and nerve signal intensity revealed sites in which the two signals covaried, but only in the medulla. Because scans were conducted in a caudorostral direction, we could constrain the analysis to the medulla by only examining the first 1 s of the fMRI and nerve signals. Increases in MSNA were associated with robust bilateral increases in signal intensity in the dorsolateral region of the medulla that corresponds to the human equivalent of the rostal ventrolateral medulla (RVLM). Reciprocal decreases in signal intensity occurred in the regions of the nucleus tractus solitarius (NTS) and caudal ventrolateral medulla (CVLM). Group analysis also revealed increases in signal intensity in the caudal pressor area (CPA), medullary raphé (MR), and dorsal motor nucleus of the vagus (DMX). We have shown for the first time that this combined approach of recording sympathetic neural activity and fMRI provides real-time imaging of the neural processes responsible for the generation of sympathetic nerve activity in awake human subjects.