ObjectivePost-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.Methods70 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.ResultsThe 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.ConclusionsPatients 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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Mild traumatic brain injury (TBI) is considered to induce abnormal intrinsic functional connectivity within resting-state networks (RSNs). The objective of this study was to estimate the role of sex in intrinsic functional connectivity after acute mild TBI. We recruited a cohort of 54 patients (27 males and 27 females with mild TBI within 7 days post-injury) from the emergency department (ED) and 34 age-, education-matched healthy controls (HCs; 17 males and 17 females). On the clinical scales, there were no statistically significant differences between males and females in either control group or mild TBI group. To detect whether there was abnormal sex difference on functional connectivity in RSNs, we performed independent component analysis (ICA) and a dual regression approach to investigate the between-subject voxel-wise comparisons of functional connectivity within seven selected RSNs. Compared to female patients, male patients showed increased intrinsic functional connectivity in motor network, ventral stream network, executive function network, cerebellum network and decreased connectivity in visual network. Further analysis demonstrated a positive correlation between the functional connectivity in executive function network and insomnia severity index (ISI) scores in male patients (r = 0.515, P = 0.006). The abnormality of the functional connectivity of RSNs in acute mild TBI showed the possibility of brain recombination after trauma, mainly concerning male-specific.

The main objective of this study was to evaluate sex differences in cortical thickness after acute mild traumatic brain injury (mTBI) and its associations with clinical outcomes. Thirty-two patients with mTBI at acute phase (2.4 ± 1.3 days post-injury) and 30 healthy controls were enrolled. All the participants underwent comprehensive neurocognitive assessments and MRI to assess cortical thickness. Significant sex differences were determined by using variance analysis of factorial design. Relations between the cortical thickness and clinical assessments were measured with the Spearman Correlation. Results revealed that patients with mTBI had significantly reduced cortical thickness in the left entorhinal cortex while increased cortical thickness in the left precuneus cortex and right lateral occipital cortex, compared with healthy controls. The interaction effect of the group × sex on cortical thickness was significant. Female patients had significant thicker cortical thickness in the left caudal anterior cingulate cortex (ACC) than male patients and had higher scores on Posttraumatic stress disorder Checklist—Civilian Version (PCL-C). Spearman correlational analysis showed a significantly positive correlations between the cortical thickness of the left caudal ACC and PCL-C ratings in female patients. Sex differences in cortical thickness support its potential as a neuroimaging phenotype for investigating the differences in clinical profiles of mild TBI between women and men.