Dataset Information

Graph Analysis of Functional Brain Networks in Patients with Mild Traumatic Brain Injury.

ABSTRACT: Mild traumatic brain injury (mTBI) is one of the most common neurological disorders worldwide. Posttraumatic complaints are frequently reported, interfering with outcome. However, a consistent neural substrate has not yet been found. We used graph analysis to further unravel the complex interactions between functional brain networks, complaints, anxiety and depression in the sub-acute stage after mTBI. This study included 54 patients with uncomplicated mTBI and 20 matched healthy controls. Posttraumatic complaints, anxiety and depression were measured at two weeks post-injury. Patients were selected based on presence (n = 34) or absence (n = 20) of complaints. Resting-state fMRI scans were made approximately four weeks post-injury. High order independent component analysis resulted in 89 neural components that were included in subsequent graph analyses. No differences in graph measures were found between patients with mTBI and healthy controls. Regarding the two patient subgroups, degree, strength, local efficiency and eigenvector centrality of the bilateral posterior cingulate/precuneus and bilateral parahippocampal gyrus were higher, and eigenvector centrality of the frontal pole/ bilateral middle & superior frontal gyrus was lower in patients with complaints compared to patients without complaints. In patients with mTBI, higher degree, strength and eigenvector centrality of default mode network components were related to higher depression scores, and higher degree and eigenvector centrality of executive network components were related to lower depression scores. In patients without complaints, one extra module was found compared to patients with complaints and healthy controls, consisting of the cingulate areas. In conclusion, this research extends the knowledge of functional network connectivity after mTBI. Specifically, our results suggest that an imbalance in the function of the default mode- and executive network plays a central role in the interaction between emotion regulation and the persistence of posttraumatic complaints.

SUBMITTER: van der Horn HJ

PROVIDER: S-EPMC5271400 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Graph Analysis of Functional Brain Networks in Patients with Mild Traumatic Brain Injury.

van der Horn Harm J HJ Liemburg Edith J EJ Scheenen Myrthe E ME de Koning Myrthe E ME Spikman Jacoba M JM van der Naalt Joukje J

PloS one 20170127 1

Mild traumatic brain injury (mTBI) is one of the most common neurological disorders worldwide. Posttraumatic complaints are frequently reported, interfering with outcome. However, a consistent neural substrate has not yet been found. We used graph analysis to further unravel the complex interactions between functional brain networks, complaints, anxiety and depression in the sub-acute stage after mTBI. This study included 54 patients with uncomplicated mTBI and 20 matched healthy controls. Postt ...[more]

PMID: 28129397

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Project description:Concussive injury (or mild traumatic brain injury; mTBI) can exhibit features of focal or diffuse injury patterns. We compared and contrasted the cellular and molecular responses after mild controlled cortical impact (mCCI; a focal injury) or fluid percussion injury (FPI; a diffuse injury) in rats. The rationale for this comparative analysis was to investigate the brain's response to mild diffuse versus mild focal injury to identify common molecular changes triggered by these injury modalities and to determine the functional pathways altered after injury that may provide novel targets for therapeutic intervention. Microarrays containing probes against 21,792 unique messenger RNAs (mRNAs) were used to investigate the changes in cortical mRNA expression levels at 3 and 24 h postinjury. Of the 354 mRNAs with significantly altered expression levels after mCCI, over 89% (316 mRNAs) were also contained within the mild FPI (mFPI) data set. However, mFPI initiated a more widespread molecular response, with over 2300 mRNAs differentially expressed. Bioinformatic analysis of annotated gene ontology molecular function and biological pathway terms showed a significant overrepresentation of genes belonging to inflammation, stress, and signaling categories in both data sets. We therefore examined changes in the protein levels of a panel of 23 cytokines and chemokines in cortical extracts using a Luminex-based bead immunoassay and detected significant increases in macrophage inflammatory protein (MIP)-1α (CCL3), GRO-KC (CXCL1), interleukin (IL)-1α, IL-1β, and IL-6. Immunohistochemical localization of MIP-1α and IL-1β showed marked increases at 3 h postinjury in the cortical vasculature and microglia, respectively, that were largely resolved by 24 h postinjury. Our findings demonstrate that both focal and diffuse mTBI trigger many shared pathobiological processes (e.g., inflammatory responses) that could be targeted for mechanism-based therapeutic interventions.

Project description:BackgroundThis study was conducted to investigate topological changes in large-scale functional connectivity (FC) and structural connectivity (SC) networks in acute mild traumatic brain injury (mTBI) and determine their potential relevance to cognitive impairment.MethodsSeventy-one patients with acute mTBI (29 males, 42 females, mean age 43.54 years) from Nanjing First Hospital and 57 matched healthy controls (HC) (33 males, 24 females, mean age 46.16 years) from the local community were recruited in this prospective study. Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were acquired within 14 days (mean 3.29 days) after the onset of mTBI. Then, large-scale FC and SC networks with 116 regions from the automated anatomical labeling (AAL) brain atlas were constructed. Graph theory analysis was used to analyze global and nodal metrics. Finally, correlations were assessed between topological properties and neurocognitive performances evaluated by the Montreal Cognitive Assessment (MoCA). Bonferroni correction was performed out for multiple comparisons in all involved analyses.ResultsCompared with HC, acute mTBI patients had a higher normalized clustering coefficient (γ) for FC (Cohen's d=4.076), and higher γ and small worldness (σ) for SC (Cohen's d=0.390 and Cohen's d=0.395). The mTBI group showed aberrant nodal degree (Dc), nodal efficiency (Ne), and nodal local efficiency (Nloc) for FC and aberrant Dc, nodal betweenness (Bc), nodal clustering coefficient (NCp) and Ne for SC mainly in the frontal and temporal, cerebellum, and subcortical areas. Acute mTBI patients also had higher functional-structural coupling strength at both the group and individual levels (Cohen's d=0.415). These aberrant global and nodal topological properties at functional and structural levels were associated with attention, orientation, memory, and naming performances (all P<0.05).ConclusionsOur findings suggested that large-scale FC and SC network changes, higher correlation between FC and SC and cognitive impairment can be detected in the acute stage of mTBI. These network aberrances may be a compensatory mechanism for cognitive impairment in acute mTBI patients.

Project description:ImportanceTraumatic brain injury (TBI) affects millions of people in the US each year. Most patients with TBI seen in emergency departments (EDs) have a Glasgow Coma Scale (GCS) score of 15 and a head computed tomography (CT) scan showing no acute intracranial traumatic injury (negative head CT scan), yet the short-term and long-term functional outcomes of this subset of patients remain unclear.ObjectiveTo describe the 2-week and 6-month recovery outcomes in a cohort of patients with mild TBI with a GCS score of 15 and a negative head CT scan.Design, setting, and participantsThis cohort study analyzed participants who were enrolled from January 1, 2014, to December 31, 2018, in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective, observational cohort study of patients with TBI that was conducted in EDs of 18 level I trauma centers in urban areas. Of the total 2697 participants in the TRACK-TBI study, 991 had a GCS score of 15 and negative head CT scan and were eligible for inclusion in this analysis. Data were analyzed from September 1, 2021, to May 30, 2022.Main outcomes and measuresThe primary outcome was the Glasgow Outcome Scale-Extended (GOS-E) score, which was stratified according to functional recovery (GOS-E score, 8) vs incomplete recovery (GOS-E score, <8), at 2 weeks and 6 months after the injury. The secondary outcome was severity of mild TBI-related symptoms assessed by the Rivermead Post Concussion Symptoms Questionnaire (RPQ) total score.ResultsA total of 991 participants (mean [SD] age, 38.5 [15.8] years; 631 male individuals [64%]) were included. Of these participants, 751 (76%) were followed up at 2 weeks after the injury: 204 (27%) had a GOS-E score of 8 (functional recovery), and 547 (73%) had a GOS-E scores less than 8 (incomplete recovery). Of 659 participants (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery. Most participants with incomplete recovery reported that they had not returned to baseline or preinjury life (88% [479 of 546]; 95% CI, 85%-90%). Mean RPQ score was 16 (95% CI, 14-18; P < .001) points lower at 2 weeks (7 vs 23) and 18 (95% CI, 16-20; P < .001) points lower at 6 months (4 vs 22) in participants with a GOS-E score of 8 compared with those with a GOS-E score less than 8.Conclusions and relevanceThis study found that most participants with a GCS score of 15 and negative head CT scan reported incomplete recovery at 2 weeks and 6 months after their injury. The findings suggest that emergency department clinicians should recommend 2-week follow-up visits for these patients to identify those with incomplete recovery and to facilitate their rehabilitation.

Project description:Despite an increasing amount of specific correlation studies between structural and functional connectivity, there is still a need for combined studies, especially in pathological conditions. Impairments of brain white matter (WM) and diffuse axonal injuries are commonly suspected to be responsible for the disconnection hypothesis in traumatic brain injury (TBI) patients. Moreover, our previous research on TBI patients shows a strong relationship between abnormalities in topological organization of brain networks and behavioral deficits. In this study, we combined task-related functional connectivity (using event-related fMRI) with structural connectivity (derived from fiber tractography using diffusion MRI data) estimates in the same participants (17 adults with TBI and 16 controls), allowing for direct comparison between graph metrics of the different imaging modalities. Connectivity matrices were computed covering the switching motor network, which includes the basal ganglia, anterior cingulate cortex/supplementary motor area, and anterior insula/inferior frontal gyrus. The edges constituting this network consisted of the partial correlations between the fMRI time series from each node of the switching motor network. The interregional anatomical connections between the switching-related areas were determined using the fiber tractography results. We found that graph metrics and hubs obtained showed no agreement in both groups. The topological properties of brain functional networks could not be solely accounted for by the properties of the underlying structural networks. However, combining complementary information from both imaging modalities could improve accuracy in prediction of switching performance. Direct comparison between functional task-related and anatomical structural connectivity, presented here for the first time in TBI patients, links two powerful approaches to map the patterns of brain connectivity that may underlie behavioral deficits in brain-injured patients.

Dataset Information

Graph Analysis of Functional Brain Networks in Patients with Mild Traumatic Brain Injury.

Publications

Graph Analysis of Functional Brain Networks in Patients with Mild Traumatic Brain Injury.

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