{
  "abstract": "Introduction. Given interest in vagus nerve stimulation (VNS) as a potential therapy for Alzheimer's disease, due to its hypothesized influence on the noradrenergic (NA) system, there is a need to understand the pronounced individual differences in responsiveness to VNS in aging. We tested whether a genetic polymorphism related to NA signaling, the {Delta}301-303 deletion in the ADRA2B receptor, modulates transcutaneous auricular (taVNS) effects on task-related pupillary responses or pupil-linked cortical activity in noradrenergic projection territory. Methods. Forty-one adults (61% deletion carriers; ages 19-79) performed a visual oddball task during a sham-controlled single-blind crossover taVNS trial. Of these people, 25 (68% deletion carriers) also performed the same task with simultaneous fMRI. Results. ADRA2B genotype predicted the taVNS effect on oddball pupillary responses (t(37) = 3.03, p = .004, d = 0.84). Deletion carrier responses were more likely to increase, while non-carrier responses decreased. Carriers showed stronger spatial alignment between pupil-BOLD coupling and cortical norepinephrine transporter (NET) expression (t(22) = 2.82, p = .010, adjusted d = 1.21). This difference was selective to NET among 19 PET maps (all other p > .11). The individual effect of taVNS predicted NET alignment of pupil-BOLD coupling ({rho} = .45, p = .023). Conclusions. ADRA2B {Delta}301-303 deletion status, which is thought to increase NA availability, predicts the direction of the pupillary response to taVNS and how tightly pupil-linked BOLD activity aligns with cortical noradrenergic projection territory.",
  "abstract_shown": true,
  "affiliations": [
    "Cornell University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "E. Riley"
    },
    {
      "name": "S. A. Mabry"
    },
    {
      "name": "M. K. MacMillan"
    },
    {
      "name": "L. Ko"
    },
    {
      "name": "F. A. Middleton"
    },
    {
      "name": "E. De Rosa"
    },
    {
      "name": "A. K. Anderson"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/61hb91bdnjx60.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.03.763718",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763718v1.full",
  "id": "61hb91bdnjx60",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763718v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763718v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/61hb91bdnjx60.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T00:21:33Z",
      "native_id": "10.64898/2026.11.03.763718",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763718v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "ADRA2B genetic polymorphism modulates vagus nerve stimulation response",
  "title_text": "ADRA2B genetic polymorphism modulates vagus nerve stimulation response",
  "type": "preprint",
  "updated_at": "2026-11-05T00:20:56Z",
  "url": "https://research.draconitic.com/paper/61hb91bdnjx60",
  "venue": "bioRxiv",
  "versions": []
}