Boosting mind-body mechanisms for mitigating autonomic dysfunction in migraine

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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.