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.
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XN and LB contributed equally.
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.
Patient consent for publication Obtained.
Ethics approval The Second Affiliated Hospital of Wenzhou Medical University.
Provenance and peer review Not commissioned; externally peer reviewed.
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