Acute hypernatremia increases functional connectivity of NaCl sensing regions in the human brain: An fMRI pilot study

Rodent studies demonstrated specialized sodium chloride (NaCl) sensing neurons in the circumventricular organs, which mediate changes in sympathetic nerve activity, arginine vasopressin, thirst, and blood pressure. However, the neural pathways involved in NaCl sensing in the human brain are incompletely understood. The purpose of this pilot study was to determine if acute hypernatremia alters the functional connectivity of NaCl-sensing regions of the brain in healthy young adults. Resting-state fMRI scans were acquired in 13 participants at baseline and during a 30 min hypertonic saline infusion (HSI). We used a seed-based approach to analyze the data, focusing on the subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) as regions of interest (ROIs). Blood chemistry and perceived thirst were assessed pre- and post-infusion. As expected, serum sodium increased from pre- to post-infusion in the HSI group. The primary finding of this pilot study was that the functional connectivity between the SFO and a cluster within the OVLT increased from baseline to the late-phase of the HSI. Bidirectional connectivity changes were found with cortical regions, with some regions showing increased connectivity with sodium-sensing regions while others showed decreased connectivity. Furthermore, the functional connectivity between the SFO and the posterior cingulate cortex (a control ROI) did not change from baseline to the late-phase of the HSI. This finding indicates a distinct response within the NaCl sensing network in the human brain specifically related to acute hypernatremia that will need to be replicated in large-scale studies.