Stimulus frequency modulates brainstem response to respiratory-gated transcutaneous auricular vagus nerve stimulation

Roberta Sclocco; Ronald G Garcia; Norman W Kettner; Harrison P Fisher; Kylie Isenburg; Maya Makarovsky; Jessica A Stowell; Jill Goldstein; Riccardo Barbieri; Vitaly Napadow

doi:10.1016/j.brs.2020.03.011

Stimulus frequency modulates brainstem response to respiratory-gated transcutaneous auricular vagus nerve stimulation

Brain Stimul. 2020 Jul-Aug;13(4):970-978. doi: 10.1016/j.brs.2020.03.011. Epub 2020 Mar 27.

Authors

Affiliations

¹ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Radiology, Logan University, Chesterfield, MO, USA. Electronic address: roberta@nmr.mgh.harvard.edu.
² Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; School of Medicine, Universidad de Santander (UDES), Bucaramanga, Colombia.
³ Department of Radiology, Logan University, Chesterfield, MO, USA.
⁴ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
⁵ Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Electronics, Information and Bioengineering, Politecnico di Milano, Italy; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Radiology, Logan University, Chesterfield, MO, USA.

Abstract

Background: The therapeutic potential of transcutaneous auricular VNS (taVNS) is currently being explored for numerous clinical applications. However, optimized response for different clinical indications may depend on specific neuromodulation parameters, and systematic assessments of their influence are still needed to optimize this promising approach.

Hypothesis: We proposed that stimulation frequency would have a significant effect on nucleus tractus solitarii (NTS) functional MRI (fMRI) response to respiratory-gated taVNS (RAVANS).

Methods: Brainstem fMRI response to auricular RAVANS (cymba conchae) was assessed for four different stimulation frequencies (2, 10, 25, 100 Hz). Sham (no current) stimulation was used to control for respiration effects on fMRI signal.

Results: Our findings demonstrated that RAVANS delivered at 100 Hz evoked the strongest brainstem response, localized to a cluster in the left (ipsilateral) medulla and consistent with purported NTS. A co-localized, although weaker, response was found for 2 Hz RAVANS. Furthermore, RAVANS delivered at 100 Hz also evoked stronger fMRI responses for important monoamine neurotransmitter source nuclei (LC, noradrenergic; MR, DR, serotonergic) and pain/homeostatic regulation nuclei (i.e. PAG).

Conclusion: Our fMRI results support previous localization of taVNS afference to pontomedullary aspect of NTS in the human brainstem, and demonstrate the significant influence of the stimulation frequency on brainstem fMRI response.

Keywords: Locus Coeruleus; Medulla; Raphe; fMRI; tVNS.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Brain Stem / diagnostic imaging
Brain Stem / physiology*
Female
Humans
Magnetic Resonance Imaging
Male
Respiration*
Transcutaneous Electric Nerve Stimulation / methods*
Vagus Nerve / physiology
Vagus Nerve Stimulation / methods*

Abstract

Publication types

MeSH terms

Grants and funding