Health & Fitness

Causal influence of brainstem response to transcutaneous vagus nerve stimulation on cardiovagal outflow TAVNS

Kristen Sparrow • November 05, 2023

serene, misty park bench
North Lake, Golden Gate Park, San Francisco.

I link to this article because I know the author Vitaly Napadow, we’ve been colleagues for over 20 years now. Hard to believe!  What they show is that, indeed, TAVNS causes engagement of brainstem circuitry that’s involved in brain autonomic outflow linking to the heart and vagus.

” For instance, transcutaneous vagus nerve stimulation (tVNS) approaches targeting the auricular branch of the vagus nerve elicit brainstem activation and HRV responses, with clinical applications for multiple disorders, producing antinociceptive effects in pelvic pain [26] and modulating the trigeminal sensory brain circuitry in migraine [19].

Toschi, N., Duggento, A., Barbieri, R., Garcia, R. G., Fisher, H. P., Kettner, N. W., Napadow, V., & Sclocco, R. (2023). Causal influence of brainstem response to transcutaneous vagus nerve stimulation on cardiovagal outflow. Brain Stimulation.


The autonomic response to transcutaneous auricular vagus nerve stimulation (taVNS) has been linked to the engagement of brainstem circuitry modulating autonomic outflow. However, the physiological mechanisms supporting such efferent vagal responses are not well understood, particularly in humans.


We present a paradigm for estimating directional brain-heart interactions in response to taVNS. We propose that our approach is able to identify causal links between the activity of brainstem nuclei involved in autonomic control and cardiovagal outflow.


We adopt an approach based on a recent reformulation of Granger causality that includes permutation-based, nonparametric statistics. The method is applied to ultrahigh field (7T) functional magnetic resonance imaging (fMRI) data collected on healthy subjects during taVNS.


Our framework identified taVNS-evoked functional brainstem responses with superior sensitivity compared to prior conventional approaches, confirming causal links between taVNS stimulation and fMRI response in the nucleus tractus solitarii (NTS). Furthermore, our causal approach elucidated potential mechanisms by which information is relayed between brainstem nuclei and cardiovagal, i.e., high-frequency heart rate variability, in response to taVNS. Our findings revealed that key brainstem nuclei, known from animal models to be involved in cardiovascular control, exert a causal influence on taVNS-induced cardiovagal outflow in humans.


Our causal approach allowed us to noninvasively evaluate directional interactions between fMRI BOLD signals from brainstem nuclei and cardiovagal outflow.