Article Text

Download PDFPDF
Research paper
Disruption of periaqueductal grey-default mode network functional connectivity predicts persistent post-traumatic headache in mild traumatic brain injury
  1. Xuan Niu1,
  2. Lijun Bai2,
  3. Yingxiang Sun1,
  4. Shan Wang2,
  5. Jieli Cao2,
  6. Chuanzhu Sun2,
  7. Zhuonan Wang1,
  8. Hui Xu1,2,
  9. Shuoqiu Gan1,2,
  10. Geng Fan2,
  11. Wenmin Huang2,
  12. Chenghui Gu3,
  13. Bo Yin3,
  14. Guanghui Bai4,
  15. Xiaoling Xu1,
  16. Ming Zhang1
  1. 1Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
  2. 2The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, China
  3. 3Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Xi’an, China
  4. 4Department of Radiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Xi‘an, China
  1. Correspondence to Dr Lijun Bai, The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; bailijun{at}xjtu.edu.cn; Professor Ming Zhang, Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710049, China; zhangming01{at}mail.xjtu.edu.cn

Abstract

Objective Post-traumatic headache (PTH) is one of the most frequent and persistent physical symptoms following mild traumatic brain injury (mTBI) and develop in more than 50% of this population. This study aimed to investigate the periaqueductal grey (PAG)-seeded functional connectivity (FC) in patients with mTBI with acute post-traumatic headache (APTH) and further examine whether the FC can be used as a neural biomarker to identify patients developing chronic pain 3 months postinjury.

Methods 70 patients with mTBI underwent neuropsychological measurements and MRI scans within 7 days postinjury and 56 (80%) of patients were followed up at 3 months. 46 healthy controls completed the same protocol on recruitment to the study. PAG-seeded resting-state FC analysis was measured in 54 patients with mTBI with APTH, in comparison with 46 healthy volunteers.

Results The mTBI+APTH group presented significantly reduced PAG-seeded FC within the default mode network (DMN), compared with healthy volunteers group. The connectivity strength can also predict patients’ complaints on the impact of headache on their lives. Crucially, the initial FC strength between the PAG-right precuneus as well as the PAG-right inferior parietal lobule became the important predictor to identify patients with mTBI developing persistent PTH 3 months postinjury.

Conclusions Patients with mTBI+APTH exhibited significant PAG-related FC differences mainly within the DMN. These regions extended beyond traditional pain processing areas and may reflect the diminished top-down attention regulation of pain perception through antinociceptive descending modulation network. The disrupted PAG-DMN FC may be used as an early imaging biomarker to identify patients at risk of developing persistent PTH.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Footnotes

  • XN and LB contributed equally.

  • Correction notice Since this paper first published, the section 'In addition, postconcussive symptoms were measured with the Rivermead Post-Concussion Symptoms Questionnaire (RPQ…' has been updated to read 'In addition, postconcussive symptoms were measured using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ)33. One item from the International Classification of Diseases-10th edition (ICD-10) diagnostic criteria (fear of brain damage with a hypochondriacal concern) was used to assess the excessive attention to brain injury self and current symptom, ranging from 0 to 4, with 0 meaning ‘not experienced’ and 4 meaning ‘severe problem’'. Three new references have also been cited at the end of the paragraph. These are listed as references 34, 35 and 36 in the reference list.

  • Contributors Study concept and design: MZ and LB. Acquisition of data: CG, BY and GB. Data analysis: XN, SW, JC, CS, ZW, HX and SG. Drafting of the manuscript: LB and XN. Statistical analysis: XN, YS, GF, XX and WH. Final approval of the version to be published: all authors.

  • Funding This research was supported by the National Natural Science Foundation of China under grant numbers 81571752, 81771914 and 81571640, Shanxi Nova Program (2014KJXX-34), the National Key Research and Development Plan of China (2016YFC0100300), the Zhejiang Natural Science Foundation (grant no LY15H090016), and Wenzhou Municipal Sci-Tech Bureau (Y20140577).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.