Mild traumatic brain injury (mTBI) is the most common neurological insult and leads to long-lasting cognitive impairments. The immune system modulates brain functions and plays a key role in cognitive deficits, however, the relationship between TBI-induced changes in inflammation-related cytokine levels and cognitive consequences is unclear. This was investigated in the present study in two cohorts of individuals within 1 week of mTBI (n = 52, n = 43) and 54 matched healthy control subjects. Patients with mTBI were also followed up at 1 and 3 months post-injury. Measures included cognitive assessments and a 9-plex panel of serum cytokines including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, IL-12, chemokine ligand 2 (CCL2), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). The contribution of cytokine levels to cognitive function was evaluated by multivariate linear regression analysis. The results showed that serum levels of IL-1β, IL-6, and CCL2 were acutely elevated in mTBI patients relative to controls; CCL2 level was remained high over 3 months whereas IL-1β and IL-6 levels were declined by 3 months post-injury. A high level of CCL2 was associated with greater severity of post-concussion symptoms (which survived in the multiple testing correction); elevated IL-1β was associated with worse working memory in acute phase (which failed in correction); and acute high CCL2 level predicted higher information processing speed at 3 months post-injury (which failed in correction). Thus, acute serum cytokine levels are useful for evaluating post-concussion symptoms and predicting cognitive outcome in participants with mTBI.

This study aimed to investigate the changes of α-synuclein in serum and its relationship with default mode network (DMN) connectivity after acute mild traumatic brain injury (mild TBI). Fifty-two patients with mild TBI at the acute phase and 47 matched healthy controls were enrolled in the study. All participants received resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessments. Relations between the levels of α-synuclein in serum and clinical assessments were obtained using multivariate linear regression. Results showed that the patients with lower α-synuclein presented more complaints on post-concussion symptoms and depression. Moreover, patients with high levels of α-synuclein exhibited significantly decreased functional connectivity in the left precuneus and increased functional connectivity in both the left anterior cingulate cortex and ventro-medial prefrontal cortex (MPFC) compared with patients with low levels of α-synuclein. These findings supported that α-synuclein may modulate the functional connectivity within the DMN and suggest the feasibility of using α-synuclein as an objective biomarker for diagnosis and prognosis of mild TBI.

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.

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.

PurposeTo investigate changes in local spontaneous brain activity in patients with active thyroid-associated ophthalmopathy (TAO) and explore the relationship between such alterations and microvascular indices.MethodsThirty-six active TAO patients with active phase and 39 healthy controls (HCs) were enrolled in this study. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI), neuropsychological tests, and ophthalmological examinations. The rs-fMRI-based fractional low-frequency fluctuation amplitude (fALFF) analysis methods were used to assess spontaneous brain activity in both groups. The structure (peripapillary retinal nerve fiber layer, pRNFL) and microvascular indices (the optic nerve head (ONH) whole image vessel density, ONH-wiVD, and peripapillary vessel density) were analyzed through optical coherence tomographic angiography imaging. The relationship between abnormal spontaneous brain activity and ophthalmological indices was analyzed using the Spearman’s rank correlation analysis.ResultsCompared with HCs, active TAO patients had increased fALFF in the right inferior temporal gyrus (R.ITG) and left posterior cingulate gyrus (L.PCC), but decreased fALFF in the right calcarine (R.CAL). The fALFF values in L.PCC were positively correlated with peripapillary vessel density, whereas fALFF values in R.CAL were negatively related to peripapillary vessel density.ConclusionsThis study demonstrates that changes in spontaneous brain activity of active TAO are accompanied by peripapillary microvascular variations. These results provide insights into the pathophysiological mechanisms of active TAO. In addition, the combination of fALFF values and peripapillary vessel density may be served as important references for better clinical decision making.