World's First Comprehensive Human Vagus Nerve Atlas: New Coordinates for Precision Neuromodulation

Introduction: A Tribute to the Donors

On July 27, 2026, the Feinstein Institutes for Medical Research, part of Northwell Health in the United States, announced the release of the world's first comprehensive anatomical atlas of the human vagus nerve to the research community. According to the announcement, over approximately three years the team obtained bilateral vagus nerves from dozens of body donors and combined dissection, ultrasound, microCT, and immunohistochemistry to create a multiscale, multimodal map of the human vagus nerve.

This achievement began not with a particular instrument, but with the decisions made by the donors and their families. Every nerve segment and every tissue section reflects an act of trust in medical progress. It is important to note that a 'comprehensive atlas' is not the same as a completed 'definitive map': the publicly available data are still expanding. What this resource provides is an unprecedented coordinate system, not a standard answer to every question.

Figure 1. Microscopic cross-section of the human vagus nerve. Fluorescent labeling clearly reveals the densely packed nerve fibers and their fascicular organization.

Research Background: The Challenge Within a Single Nerve

The vagus nerve is cranial nerve X (CN X), with one nerve on each side. It arises from the brainstem, passes through the neck and thorax, and extends into the abdomen. It carries information about visceral state back to the brain while transmitting regulatory commands from the brain to the heart, lungs, gastrointestinal tract, and other organs. It participates in cardiopulmonary function, digestion, and neuroimmune reflexes. A single vagus nerve contains roughly 100,000 fibers, some of which are unmyelinated fibers approximately 0.5 μm in diameter.

The challenge is that these roughly 100,000 fibers do not run neatly in parallel. Instead, they are organized into numerous fascicles that split, merge, and rotate along the nerve and give rise to branches serving different tissues. Invasive vagus nerve stimulation (iVNS) has been approved for selected patients with epilepsy and treatment-resistant depression, but current devices generally stimulate an entire segment of the nerve. Selectivity is limited, and off-target fibers may be recruited at the same time. To achieve more precise neuromodulation, researchers first need to understand how the 'wires inside the cable' are arranged. In 2022, the U.S. National Institutes of Health invested approximately $6.7 million to launch this mapping project.

Figure 2. An early presentation of the human vagus nerve from the REVA project: A shows the original microscopic image, B shows the computer-enhanced image, and C presents further analysis at the level of individual nerve fibers.

Methods: A Panoramic Scan of the Nerve

The researchers first performed serial microdissections from the neck through the thorax to the abdomen, labeling branches according to the target tissues they reached and documenting the process with photographs and video. They then used ultrasound to acquire two-dimensional images and reconstruct three-dimensional volumes. The main nerve trunk was cut into 1.5 cm segments, treated in Lugol's iodine solution for one week, and scanned by micro-computed tomography (microCT) at a voxel size of 9 μm to reconstruct the three-dimensional architecture of the fascicles.

Each segment was further divided into 0.5 cm subsegments. At multiple levels, 5 μm-thick sections were prepared for hematoxylin and eosin staining and immunohistochemistry. Version 2 of the accompanying f011 dataset contains the left and right vagus nerves from one female body donor, comprising 1,351 files and approximately 3.22 TB of data. The press release uses the project-wide figure of '30 donors and 60 nerves'; the currently public collection and associated preprint support 29 donors and 58 nerves. The two totals reflect the difference between the announced project scope and the material that is currently public.

Figure 3. Example of microCT fascicle segmentation in adjacent samples C1L and C2L from the left cervical region. The pale-yellow areas indicate annotated fascicles, and the red endpoints establish correspondence across segments.

Results: What the Atlas Reveals

The central value of this resource is that it places previously fragmented anatomical information within a single coordinate framework. At the macroscopic level, it records where organ-related branches emerge from the main trunk; at the mesoscopic level, it reconstructs the number, shape, and relative positions of fascicles across different segments; and at the microscopic level, histological markers are used to characterize different fiber features. The related preprint also classifies observed branches as sympathetic, muscular, vascular, cardiac, pulmonary, esophageal, or multi-target, providing a more standardized reference for surgical localization.

However, the atlas should not be interpreted to mean that 'every fiber has been traced from the brainstem to a specific organ.' A 9 μm microCT voxel is sufficient to visualize fascicles, but not to continuously resolve individual unmyelinated fibers around 0.5 μm in diameter. Nor does the atlas directly identify 'the stimulation parameters that work best.' What it provides is the anatomical foundation that had been missing: where the fascicles lie, how they change along the nerve, and which patterns are shared across individuals. Researchers can use this foundation to improve electrode geometry and placement, build more realistic computational models, and then test in functional experiments whether target fibers are selectively activated.

Figure 4. Example of an immunohistochemical mosaic and region-of-interest numbering at a level near the pharyngeal branch/accessory nerve (cranial nerve XI) in the left cervical portion of f011.

Mechanistic Discussion: What Precision Stimulation Still Requires

Electrical stimulation does not automatically distinguish 'cardiac fibers' from 'anti-inflammatory fibers.' Axon diameter, myelination, trajectory, and distance from the electrode all influence the order in which fibers are activated. If one electrode covers several fascicles, the desired therapeutic signal may occur together with off-target effects such as hoarseness and cough. Precision neuromodulation therefore requires an evidence chain that connects the anatomical atlas, computational modeling, electrophysiological recording, and validation of physiological effects.

This is also why immunohistochemistry matters. Neurofilament (NF) helps reveal axonal structure; myelin basic protein (MBP) indicates myelinated components; choline acetyltransferase (ChAT) is associated with a cholinergic phenotype; and tyrosine hydroxylase (TH) is a marker associated with catecholaminergic fibers. These markers can suggest how different fiber types are distributed among fascicles, but color alone cannot determine which organ a given fiber ultimately reaches. One further distinction is essential: ultrasound in this dataset is an imaging method, not a validated ultrasound treatment.

Figure 5. Representative NF, MBP, TH, and ChAT immunofluorescence channels from the same tissue region.

Future Outlook: From Atlas to Therapy

This open atlas can continue to incorporate data from additional donors, helping define both individual variability and shared anatomical patterns. It can also support multi-contact electrodes and subject-specific computational models, giving researchers a stronger basis for selecting stimulation sites and parameters. In addition, it may provide an anatomical reference for exploratory studies in inflammatory bowel disease, heart failure, diabetes, and other conditions, with actual efficacy assessed through functional experiments and clinical trials.

In 2025, the U.S. Food and Drug Administration approved the SetPoint System for certain adults with moderate-to-severe active rheumatoid arthritis. That approval, however, preceded the public release of the atlas and applies under strictly defined conditions. The significance of the new atlas is that it provides a shared, computable, and verifiable coordinate system for the next generation of more precise neuromodulation.

For vagus nerve stimulation, this atlas is more than an anatomical resource; it is a human coordinate system for precision neuromodulation. Historically, electrodes often encircled an entire nerve segment, so target and off-target fibers could be recruited together, and therapeutic effects could occur alongside hoarseness, cough, and other responses. Researchers can now use the atlas to refine electrode contacts, implantation sites, and computational models, moving from a broad 'master switch' toward selective modulation of defined fascicles and organ pathways. The atlas also provides a shared foundation for multi-contact electrodes, individualized parameters, image-guided planning, and closed-loop stimulation, helping engineering, functional experiments, and clinical trials connect more effectively. It does not directly identify optimal parameters or prove efficacy, but it provides a critical starting point for reducing adverse effects, widening the therapeutic window, and exploring new indications - and moves vagus nerve stimulation closer to an addressable, programmable, and verifiable neural interface.

References

Feinstein Institutes. Feinstein Institutes unveils world's first comprehensive vagus nerve map. 2026-07-27.

Zanos, S., Jayaprakash, N., Khaled, Q., Nasrallah, Z., Barbe, M., Chen, F. L., miller, larry, Zanos, T., Levy, T. J., Vardhan, A., Cang, J., Toth, V., Coppa, K., Ben-Shalom, N., Song, W., Carpentiere, N., Kanavos, T., Birbas, E., Bahadir, S., & Saleknezhad, P. (2026). Human vagus nerve anatomical reconstruction using microCT immunohistochemistry and ultrasound - f011 [Dataset]. In SPARC REVA FEINSTEIN (Version 2). SPARC Portal. https://doi.org/10.26275/QCMB-KMBX

A standardized, surgically relevant map for emergence of organ-specific branches from the human vagus nerve. bioRxiv, 2026.

U.S. FDA. SetPoint System, PMA P240039, decision date 2025-07-30. FDA