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An individual patient data meta-analysis on vagal nerve stimulation for recovery from disorders of consciousness
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  • Published: 13 February 2026

An individual patient data meta-analysis on vagal nerve stimulation for recovery from disorders of consciousness

  • John JY Zhang1 na1,
  • Yu Tung Lo1,9 na1,
  • Alina Xiao Qian Wee2,
  • Jessica Yeo3,
  • Enhui Suan2,
  • Zheting Zhang2,
  • Mervyn Jun Rui Lim4,7 &
  • …
  • Karen Sui Geok Chua2,3,5,6,8 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Diseases
  • Engineering
  • Health care
  • Medical research
  • Neurology
  • Neuroscience

Abstract

Disorders of consciousness (DoC), including vegetative state (VS), unresponsive wakefulness syndrome (UWS), and minimally conscious state (MCS), are characterized by impaired consciousness and have limited therapeutic options. We aimed to perform a systematic review and meta-analysis of individual participant data (IPD) on the efficacy of vagal nerve stimulation (VNS) for DoC. A systematic literature search identified studies on the use of VNS in patients with DoC. IPD were extracted from included studies and pooled for analysis. The primary outcome was improvement in consciousness, assessed clinically using the Coma Recovery Scale-Revised (CRS-R). A total of 10 studies including 112 patients were identified. VNS was associated with significant improvements in consciousness, with a mean increase of 2.78 (95% CI 1.62 to 3.94) in CRS-R. 40.2% of patients demonstrated an improvement in CRS-R score above the minimal clinically important difference (MCID) of 3 or more. Patients in MCS improved more than those in coma or VS/UWS. This IPD meta-analysis provides early evidence for the efficacy of VNS in improving consciousness in patients with DoC. Our results imply the need for high-quality randomized controlled trials for both invasive and non-invasive VNS to better inform its role in DoC neuro-recovery.

Data availability

The data used for analysis in this paper are all publicly available from the included studies. There is no additional data used available for sharing. For data enquiry and requests, please contact the corresponding author.

Abbreviations

BAEP:

Brainstem auditory evoked potentials

CBF:

Cerebral blood flow

CRS-R:

Coma Recovery Scale-Revised

DBS:

Deep brain stimulation

DMN:

Default mode network

DoC:

Disorders of consciousness

EEG:

Electroencephalogram

eMCS:

Emergence from a minimally conscious state (eMCS)

fMRI:

Functional magnetic resonance imaging

HIE:

Hypoxic-ischemic encephalopathy

IPD:

Individual participant data

iVNS:

Invasive vagus nerve stimulation

MCID:

Minimal clinically significant difference

MCS:

Minimally conscious state

rTMS:

Repetitive transcranial magnetic stimulation

SCS:

Spinal cord stimulation

SEP:

Somatosensory evoked potentials

taVNS:

Transcutaneous auricular VNS

TBI:

Traumatic brain injury

tDCS:

Transcranial direct current stimulation

UWS:

Unresponsive wakefulness syndrome

VNMM:

Vagus nerve magnetic modulation

VNS:

Vagal nerve stimulation

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Author information

Author notes

  1. John J. Y. Zhang and Yu Tung Lo contributed equally to this paper.

Authors and Affiliations

  1. Department of Neurosurgery, National Neuroscience Institute, Singapore, Singapore

    John JY Zhang & Yu Tung Lo

  2. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

    Alina Xiao Qian Wee, Enhui Suan, Zheting Zhang & Karen Sui Geok Chua

  3. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Jessica Yeo & Karen Sui Geok Chua

  4. Department of Neurosurgery, National University Hospital, Singapore, Singapore

    Mervyn Jun Rui Lim

  5. Institute of Rehabilitation Excellence, Tan Tock Seng Hospital Rehabilitation Centre, Singapore, Singapore

    Karen Sui Geok Chua

  6. Rehabilitation Research Institute of Singapore, Singapore, Singapore

    Karen Sui Geok Chua

  7. National University of Singapore, Singapore, Singapore

    Mervyn Jun Rui Lim

  8. Nanyang Technological University, Singapore, Singapore

    Karen Sui Geok Chua

  9. Duke-NUS Medical School, Singapore, Singapore

    Yu Tung Lo

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Contributions

J.J.Y.Z., Y.T.L. and K.S.C. conceived the manuscript idea and designed the research study. J.J.Y.Z., Y.T.L., A.W., J.Y., E.S., and Z.Z. performed the data collection. J.J.Y.Z. and Y.T.L. analysed and interpreted the data. Y.T.L. prepared Figs. 1, 2, 3, 4, 5 and 6. J.J.Y.Z. and Y.T.L. wrote and the main manuscript text. All authors reviewed and critically revised the manuscript. Y.T.L., M.J.R.L. and K.S.C supervised the conduct of this study.

Corresponding author

Correspondence to Yu Tung Lo.

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Zhang, J.J., Lo, Y., Wee, A. et al. An individual patient data meta-analysis on vagal nerve stimulation for recovery from disorders of consciousness. Sci Rep (2026). https://doi.org/10.1038/s41598-025-32369-0

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  • Received: 06 April 2025

  • Accepted: 09 December 2025

  • Published: 13 February 2026

  • DOI: https://doi.org/10.1038/s41598-025-32369-0

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Keywords

  • Coma
  • Disorders of consciousness
  • Minimally conscious state
  • Unresponsive wakefulness syndrome
  • Vegetative state
  • Vagal nerve stimulation
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