Investigating the effects of VNS on central autonomic network and interoception

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ABSTRACT The principal source of visceral afferent information to the brain from the body is the vagus nerve. The sympathetic and parasympathetic nervous systems are the main branches of the autonomic nervous system (ANS), and they dynamically control the visceral functions to maintain body homeostasis. A hallmark of the ANS is its ability to react to environmental challenges/stressors in order to properly respond to the metabolic demands of the organism. Cervical vagus nerve stimulation (VNS) is reported to modulate ANS and in particular heart rate variability (HRV) and baroreflexes. Yet the mechanisms by which these are achieved remain unknown. Disentangling the direct VNS effects of efferent modulation versus a centrally mediated modulation via afferent fibers is key. This Supplemental Project will investigate the functional connectivity patterns of interoception and high-order brain regions as measured by cutting-edge brain functional neuroimaging methods. Most importantly, it will study their relationship to spontaneous fluctuations in blood pressure and heart rate. The REVEAL Common Study Protocol (CSP) hypothesizes that any VNS-induced changes in blood pressure will be via stimulation of afferent (sensory) fibers in the vagus nerve. This study is an alternative to test this hypothesis and will provide key mechanistic data that will complement discoveries from the CSP. By acquiring functional brain imaging before and after VNS implant and most critically, in the moment activations in response to VNS, we can ascertain whether this upstream central nervous system modulation is at the midbrain reflexive level or whether it involves higher-order brain regions. Interleaved VNSfMRI will act as a window for in-the-moment direct effects of VNS on brain activity and interoceptive processes. The cutting edge precision functional mapping will reliably map the multimodal networks involved in interoception and allostasis.