Novel Therapeutics Targeted to Neural-Cardiac Interface
Background
Our lab is developing and validating novel, nonpharmacological interventions targeting to comorbidity of depression and cardiovascular (CV) disease in a sex-dependent manner. The vagus nerve, the longest nerve in the body, connects brain to visceral organs (e.g., heart, lungs, and gut). The vagus involves regulation of cardiac activity which when dysfunctional results in mood/anxiety dysregulation and risk for cardiovascular disease. Vagus nerve stimulation (VNS) has been proposed as an intervention for regulation of CV function and depressed mood. However, VNS involves a surgery which is associated with complications.
Vagus nerve stimulation (VNS) has shown beneficial effects in the regulation of depressed mood and cardiovascular function
Vagus nerve is involved in the regulation of the body's response to stress and it is important in the modulation of mood/anxiety, heart rate, breathing, gastrointestinal function, and inflammation.
We are developing a novel neuromodulation (non-pharmacologic) therapy for depressed mood/anxiety, autonomic dysregulation, and hypertension that targets the auricular branch of the vagus nerve, the direct electrical conduit between the brain and heart, and uses our own respiration to enhance its effects. The neurobiology and physiology differ by sex.
Our Work
Our group is developing a novel, transcutaneous VNS approach involving electrical stimulation of the auricular branch of the vagus nerve (taVNS), which has demonstrated comparable effects to those obtained with invasive VNS, but safer. Further, we proposed optimization of this by synchronizing to one’s own respiration. We have shown respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) has enhanced effects in regulation of depressive/anxiety symptoms and CV function in people with major depression and CV disease. Current work is evaluating the sex-dependent impact of RAVANS on modulation of stress response circuitry and physiological dysregulation in recurrent depression (e.g., Project 2 – MGH-Harvard-CO U54 SCORE).
A Sample of Key Findings
One.
RAVANS stimulation during the exhalation is associated with greater modulation of brain nuclei involved in cardiac autonomic regulation.
Two.
Expiratory-gated (vs. inhalation) RAVANS has significant effects in reduction of depressive & anxiety symptoms and upregulation of cardiovagal activity in women with recurrent major depression.