(39) Level-dependent separation of sensory and motor fascicles in the human cervical vagus nerve

Friday, June 13, 2025

4:30 PM - 5:10 PM ET

Location: Sky View

Presenting Author(s)

NJ

Naveen Jayaprakash, PhD

Research Scientist
Feinstein Institutes for Medical Research
Manhasset, New York, United States

Co-Author(s)

NC

Nicole Carpentiere, BSc

Feinstein Institutes for Medical Research
Manhasset, New York, United States
SB

Siyar Bahadir, MD

Feinstein Institutes for Medical Research
Manhasset, New York, United States
KQ

Khaled Qanud, MD

Feinstein Institutes for Medical Research
Manhasset, New York, United States
NS

Nafiseh Saleknezhad, MD

Feinstein Institutes for Medical Research
Manhasset, New York, United States
TL

Todd Levy, MS

Feinstein Institutes for Medical Research
Manhasset, New York, United States
LC

Lucas Cang, BSc

Feinstein Institutes for Medical Research
Manhasset, New York, United States
AV

Avantika Vardhan, PhD

Feinstein Institutes for Medical Research
Manhasset, New York, United States
VT

Viktor Toth, MS

Feinstein Institutes for Medical Research
Manhasset, New York, United States
IM

Ibrahim Mughrabi, MD

Feinstein Institutes for Medical Research
Manhasset, New York, United States
TY

Tara Yari, BSc

Feinstein Institutes for Medical Research
Manhasset, New York, United States
ZN

Zeinab Nassrallah, PhD

Donald and Barbara Zucker School of Medicine
Hempstead, New York, United States
MB

Mary Barbe, PhD

Lewis Katz School of Medicine, Temple University
Philadelphia, Pennsylvania, United States
LM

Larry Miller, MD

Feinstein Institutes for Medical Research
Manhasset, New York, United States
TZ

Theodoros Zanos, PhD

Feinstein Institutes for Medical Research
Manhasset, New York, United States
Stavros Zanos, MD, PhD

Associate Professor
Feinstein Institutes for Medical Research, and Zucker School of Medicine at Hofstra/Northwell
Manhasset, New York, United States

Introduction: Vagus nerve stimulation (VNS) is emerging as a potential treatment of disorders associated with chronic inflammation. To reduce side-effects and improve the precision of VNS, it may be useful to target specifically sensory or motor fascicles in the cervical VN with spatially selective VNS. The extent to which sensory and motor fascicles are separated in the cervical VN is unknown.

Methods: Six vagus nerves were extracted from 3 embalmed cadavers, from the nodose ganglion to the subdiaphragmatic branches. Each nerve was scanned using micro-CT; 3D reconstruction of nerve fascicle trajectories was performed using Slicer software. IHC was performed in the same nerves, with stains for neurofilament (NF), myelin basic protein (MBP), choline acetyltransferase (ChAT), and tyrosine hydroxylase (TH). Based on these markers, fibers were categorized as motor fibers (NF+, MBP+, ChAT+/TH+) or sensory fibers (NF+, MBP-, ChAT-, TH-). To identify unmyelinated sensory fibers, we performed Peripherin (P+) staining; P+ fibers are NF+ but TH- and ChAT-.

Results: In micro-CT images, fascicles emerging caudally from the nodose ganglion were classified as sensory and fascicles bypassing the nodose as motor. To validate this classification, we quantified counts of sensory and motor fibers from IHC images of the same fascicles. We found that there are significantly greater sensory fiber counts in fascicles classified as sensory in micro-CT vs. fascicles classified as motor, and vice-versa for motor fibers. Fascicles with high TH+ fiber counts have low ChAT+ fiber counts; likewise, fascicles rich in ChAT+ fibers are poor in TH+ fibers.

Longitudinal tracking of fascicles in micro-CT images showed that motor and sensory fascicles merge at different levels, which vary between individuals and between the left and right vagus nerves. Almost complete mixing of sensory and motor fascicles was observed at the mid-cervical level, approximately 3 to 6 cm from the center of the nodose ganglion (level at which the ganglion's diameter is the greatest). Additionally, at least one motor fascicle in each nerve remained separate from the sensory or mixed fascicles, throughout the length of the cervical VN. Fiber count distributions within fascicles agree with the micro-CT findings of initial sensory-motor separation and progressive mixing.

Conclusion: Our anatomical findings indicate that spatial separation of sensory and motor fascicles of the human VN is present in the upper cervical and progressively disappears towards the mid-cervical portion. Placement of VNS devices above mid-cervical level may permit spatially selective activation of sensory or motor functions of the VN.