# Boosting mind-body mechanisms for mitigating autonomic dysfunction in migraine

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $357,358

## Abstract

Abstract 
 Migraine (MIG) is a prevalent (15-20%) and highly disabling disorder, with complex neurobiological 
underpinnings characterized by autonomic dysregulation. Mindfulness meditation (MM) has been proposed as 
a behavioral intervention that may improve autonomic functioning. Our own data, and those of others, found 
enhanced parasympathetic drive (as evidenced by higher levels of high-frequency heart rate variability, or HF- 
HRV), after only 8 weeks of meditation training. In addition, meditation training promotes improved emotion 
regulation and corresponding decreased activation of the amygdala in response to stressors, again as shown 
by our own data and those of others. Normalization of autonomic functioning and reduction of amygdala 
response to stressors may be an important therapeutic target in migraineurs. Multimodal approaches have 
shown improved clinical outcomes, and have been recommended in the recent Institute of Medicine report on 
pain. We propose that this is also the case for mind-body therapies. MM has shown promise for migraine, and 
likely operates by top-down mechanisms, potentially reducing amygdala reactivity as well as enhancing 
autonomic functioning, both peripherally (as assessed with HF-HRV) and centrally (as assessed with fMRI in 
the Central Autonomic Network, or CAN). 
 Additionally, bottom-up therapies such as invasive and non-invasive auricular transcutaneous vagus nerve 
stimulation (tVNS) also reduce migraine frequency and disability. In tVNS, vagal afference relayed to nucleus 
tractus solitarii (NTS) in the medulla may modulate trigeminal sensory complex excitability and hyperexcitability 
in higher brain structures (i.e., a “bottom-up” pathway). Furthermore, the dorsal medullary vagal system 
operates in synchrony with respiration: NTS receiving inhibitory inputs from medullary ventral respiratory group 
(VRG) nuclei during inhalation, and facilitatory input during expiration. This is a critically-important feature of 
this circuitry, as it suggests that interventions utilizing this NTS pathway should be synchronized with 
respiration. Hence, our group developed Respiratory-gated Auricular Vagal Afferent Nerve Stimulation 
(RAVANS), which optimizes tVNS targeting of NTS by stimulating only during the expiratory phase. Thus, 
RAVANS tVNS incorporates bottom-up modulation of cortical/subcortical hyperexcitability. In sum, we propose 
that MM training incorporating RAVANS tVNS will have a synergistic effect in enhancing (both central and 
peripheral) autonomic functioning and in mitigating amygdalar hyperactivity in response to stressors in patients 
with migraine.

## Key facts

- **NIH application ID:** 10456009
- **Project number:** 5P01AT009965-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** RANDY L Hirschtick
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $357,358
- **Award type:** 5
- **Project period:** 2018-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456009

## Citation

> US National Institutes of Health, RePORTER application 10456009, Boosting mind-body mechanisms for mitigating autonomic dysfunction in migraine (5P01AT009965-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10456009. Licensed CC0.

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