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Mild traumatic brain injury is associated with effect of inflammation on structural changes of default mode network in those developing chronic pain.

ABSTRACT: BACKGROUND:Mild traumatic brain injury (mTBI) has a higher prevalence (more than 50%) of developing chronic posttraumatic headache (CPTH) compared with moderate or severe TBI. However, the underlying neural mechanism for CPTH remains unclear. This study aimed to investigate the inflammation level and cortical volume changes in patients with acute PTH (APTH) and further examine their potential in identifying patients who finally developed CPTH at follow-up. METHODS:Seventy-seven mTBI patients initially underwent neuropsychological measurements, 9-plex panel of serum cytokines and MRI scans within 7?days post-injury (T-1) and 54 (70.1%) of patients completed the same protocol at a 3-month follow-up (T-2). Forty-two matched healthy controls completed the same protocol at T-1 once. RESULTS:At baseline, mTBI patients with APTH presented significantly increased GM volume mainly in the right dorsal anterior cingulate cortex (dACC) and dorsal posterior cingulate cortex (dPCC), of which the dPCC volume can predict much worse impact of headache on patients' lives by HIT-6 (??=?0.389, P?=?0.007) in acute stage. Serum levels of C-C motif chemokine ligand 2 (CCL2) were also elevated in these patients, and its effect on the impact of headache on quality of life was partially mediated by the dPCC volume (mean [SE] indirect effect, 0.088 [0.0462], 95% CI, 0.01-0.164). Longitudinal analysis showed that the dACC and dPCC volumes as well as CCL2 levels had persistently increased in patients developing CPTH 3?months postinjury. CONCLUSION:The findings suggested that structural remodelling of DMN brain regions were involved in the progression from acute to chronic PTH following mTBI, which also mediated the effect of inflammation processes on pain modulation. TRIAL REGISTRATION:ClinicalTrial.gov ID: NCT02868684 ; registered 16 August 2016.

SUBMITTER: Niu X

PROVIDER: S-EPMC7684719 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Mild traumatic brain injury is associated with effect of inflammation on structural changes of default mode network in those developing chronic pain.

Niu Xuan X Bai Lijun L Sun Yingxiang Y Wang Yuan Y Bai Guanghui G Yin Bo B Wang Shan S Gan Shuoqiu S Jia Xiaoyan X Liu Hongjuan H

The journal of headache and pain 20201123 1

<h4>Background</h4>Mild traumatic brain injury (mTBI) has a higher prevalence (more than 50%) of developing chronic posttraumatic headache (CPTH) compared with moderate or severe TBI. However, the underlying neural mechanism for CPTH remains unclear. This study aimed to investigate the inflammation level and cortical volume changes in patients with acute PTH (APTH) and further examine their potential in identifying patients who finally developed CPTH at follow-up.<h4>Methods</h4>Seventy-seven mT ...[more]

PMID: 33228537

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Project description:BackgroundThere is a significant number of military personnel with a history of mild traumatic brain injury (mTBI) who suffer from comorbid posttraumatic stress symptoms (PTS). Although there is evidence of disruptions of the default mode network (DMN) associated with PTS and mTBI, previous studies have only studied static connectivity while ignoring temporal variability of connectivity.ObjectiveTo assess DMN disrupted or dysregulated neurocircuitry, cognitive functioning, and psychological health of active-duty military with mTBI and PTS.MethodU.S. Army soldiers with PTS (n = 14), mTBI + PTS (n = 25), and healthy controls (n = 21) voluntarily completed a cognitive and symptom battery. In addition, participants had magnetic resonance imaging (MRI) to assess both static functional connectivity (SFC) and variance of dynamic functional connectivity (vDFC) of the DMN.ResultsBoth the PTS and mTBI + PTS groups had significant symptoms, but only the comorbid group had significant decrements in cognitive functioning. Both groups showed less stable and disrupted neural signatures of the DMN, mainly constituting the cingulate-frontal-temporal-parietal attention network. Specifically, the PTS group showed a combination of both reduced contralateral strength and reduced unilateral variability of frontal-cingulate-temporal connectivities, as well as increased variability of frontal-parietal connectivities. The mTBI + PTS group had fewer abnormal connectives than the PTS group, all of which included reduced strength of frontal-temporal regions and reduced variability frontal-cingulate-temporal regions. Greater SFC and vDFC connectivity of the left dorsolateral prefrontal cortex (dlPFC) ↔ precuneus was associated with higher cognitive scores and lower symptom scores.ConclusionsFindings suggest that individuals with PTS and mTBI + PTS have a propensity for accentuated generation of thoughts, feelings, sensations, and/or images while in a resting state. Compared with controls, only the PTS group was associated with accentuated variability of the frontal-parietal attention network. While there were no significant differences in DMN connectivity strength between the mTBI + PTS and PTS groups, variability of connectivity was able to distinguish them.

Project description:The human resting-state is characterized by spatially coherent brain activity at a low temporal frequency. The default mode network (DMN), one of so-called resting-state networks, has been associated with cognitive processes that are directed toward the self, such as introspection and autobiographic memory. The DMN's integrity appears to be crucial for mental health. For example, patients with Alzheimer's disease or other psychiatric conditions show disruptions of functional connectivity within the brain regions of the DMN. However, in prodromal or early stages of Alzheimer's disease, physiological alterations are sometimes elusive, despite manifested cognitive impairment. While functional connectivity assesses the signal correlation between brain areas, multi-scale entropy (MSE) measures the complexity of the blood-oxygen level dependent signal within an area and thus might show local changes before connectivity is affected. Hence, we investigated alterations of functional connectivity and MSE within the DMN in fifteen mild Alzheimer's disease patients as compared to fourteen controls. Potential associations of MSE with functional connectivity and cognitive abilities [i.e., mini-mental state examination (MMSE)] were assessed. A moderate decrease of DMN functional connectivity between posterior cingulate cortex and right hippocampus in Alzheimer's disease was found, whereas no differences were evident for whole-network functional connectivity. In contrast, the Alzheimer's disease group yielded lower global DMN-MSE than the control group. The most pronounced regional effects were localized in left and right hippocampi, and this was true for most scales. Moreover, MSE significantly correlated with functional connectivity, and DMN-MSE correlated positively with the MMSE in Alzheimer's disease. Most interestingly, the right hippocampal MSE was positively associated with semantic memory performance. Thus, our results suggested that cognitive decline in Alzheimer's disease is reflected by decreased signal complexity in DMN nodes, which might further lead to disrupted DMN functional connectivity. Additionally, altered entropy in Alzheimer's disease found in the majority of the scales indicated a disturbance of both local information processing and information transfer between distal areas. Conclusively, a loss of nodal signal complexity potentially impairs synchronization across nodes and thus preempts functional connectivity changes. MSE presents a putative functional marker for cognitive decline that might be more sensitive than functional connectivity alone.

Dataset Information

Mild traumatic brain injury is associated with effect of inflammation on structural changes of default mode network in those developing chronic pain.

Publications

Mild traumatic brain injury is associated with effect of inflammation on structural changes of default mode network in those developing chronic pain.

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