- Award ID(s):
- 1632849
- PAR ID:
- 10222684
- Date Published:
- Journal Name:
- Frontiers for young minds
- ISSN:
- 2296-6846
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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null (Ed.)Background: Patients with uncomplicated cases of concussion are thought to fully recover within several months as symptoms resolve. However, at the group level, undergraduates reporting a history of concussion (mean: 4.14 years post-injury) show lasting deficits in visual working memory performance. To clarify what predicts long-term visual working memory outcomes given heterogeneous performance across group members, we investigated factors surrounding the injury, including gender, number of mild traumatic brain injuries, time since mild traumatic brain injury (mTBI), loss of consciousness (LOC) (yes, no), and mTBI etiology (non-sport, team sport, high impact sport, and individual sport). We also collected low-density resting state electroencephalogram to test whether spectral power was correlated with performance. Aim: The purpose of this study was to identify predictors for poor visual working memory outcomes in current undergraduates with a history of concussion. Methods: Participants provided a brief history of their injury and symptoms. Participants also completed an experimental visual working memory task. Finally, low-density resting-state electroencephalogram was collected. Results: The key observation was that LOC at the time of injury predicted superior visual working memory years later. In contrast, visual working memory performance was not predicted by other factors, including etiology, high impact sports, or electroencephalogram spectral power. Conclusions: Visual working memory deficits are apparent at the group level in current undergraduates with a history of concussion. LOC at the time of concussion predicts less impaired visual working memory performance, whereas no significant links were associated with other factors. One interpretation is that after LOC, patients are more likely to seek medical advice than without LOC. Relevance for patients: Concussion is a head injury associated with future cognitive changes in some people. Concussion should be taken seriously, and medical treatment sought whenever a head injury occurs.more » « less
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null (Ed.)Abstract Mild traumatic brain injury (mTBI), or concussion, accounts for 85% of all TBIs. Yet survivors anticipate full cognitive recovery within several months of injury, if not sooner, dependent upon the specific outcome/measure. Recovery is variable and deficits in executive function, e.g., working memory (WM) can persist years post-mTBI. We tested whether cognitive deficits persist in otherwise healthy undergraduates, as a conservative indicator for mTBI survivors at large. We collected WM performance (change detection, n-back tasks) using various stimuli (shapes, locations, letters; aurally presented numbers and letters), and wide-ranging cognitive assessments (e.g., RBANS). We replicated the observation of a general visual WM deficit, with preserved auditory WM. Surprisingly, visual WM deficits were equivalent in participants with a history of mTBI (mean 4.3 years post-injury) and in undergraduates with recent sports-related mTBI (mean 17 days post-injury). In seeking the underlying mechanism of these behavioral deficits, we collected resting state fMRI (rsfMRI) and EEG (rsEEG). RsfMRI revealed significantly reduced connectivity within WM-relevant networks (default mode, central executive, dorsal attention, salience), whereas rsEEG identified no differences (modularity, global efficiency, local efficiency). In summary, otherwise healthy current undergraduates with a history of mTBI present behavioral deficits with evidence of persistent disconnection long after full recovery is expected.more » « less
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Abstract Background The use of blood biomarkers after mild traumatic brain injury (mTBI) has been widely studied. We have identified eight unresolved issues related to the use of five commonly investigated blood biomarkers: neurofilament light chain, ubiquitin carboxy-terminal hydrolase-L1, tau, S100B, and glial acidic fibrillary protein. We conducted a focused literature review of unresolved issues in three areas: mode of entry into and exit from the blood, kinetics of blood biomarkers in the blood, and predictive capacity of the blood biomarkers after mTBI.
Findings Although a disruption of the blood brain barrier has been demonstrated in mild and severe traumatic brain injury, biomarkers can enter the blood through pathways that do not require a breach in this barrier. A definitive accounting for the pathways that biomarkers follow from the brain to the blood after mTBI has not been performed. Although preliminary investigations of blood biomarkers kinetics after TBI are available, our current knowledge is incomplete and definitive studies are needed. Optimal sampling times for biomarkers after mTBI have not been established. Kinetic models of blood biomarkers can be informative, but more precise estimates of kinetic parameters are needed. Confounding factors for blood biomarker levels have been identified, but corrections for these factors are not routinely made. Little evidence has emerged to date to suggest that blood biomarker levels correlate with clinical measures of mTBI severity. The significance of elevated biomarker levels thirty or more days following mTBI is uncertain. Blood biomarkers have shown a modest but not definitive ability to distinguish concussed from non-concussed subjects, to detect sub-concussive hits to the head, and to predict recovery from mTBI. Blood biomarkers have performed best at distinguishing CT scan positive from CT scan negative subjects after mTBI.
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Abstract Children who experience a traumatic brain injury (TBI) are at elevated risk for a range of negative cognitive and neuropsychological outcomes. Identifying which children are at greatest risk for negative outcomes can be difficult due to the heterogeneity of TBI. To address this barrier, the current study applied a novel method of characterizing brain connectivity networks, Bayesian multi‐subject vector autoregressive modelling (BVAR‐connect), which used white matter integrity as priors to evaluate effective connectivity—the time‐dependent relationship in functional magnetic resonance imaging (fMRI) activity between two brain regions—within the default mode network (DMN). In a prospective longitudinal study, children ages 8–15 years with mild to severe TBI underwent diffusion tensor imaging and resting state fMRI 7 weeks after injury; post‐concussion and anxiety symptoms were assessed 7 months after injury. The goals of this study were to (1) characterize differences in positive effective connectivity of resting‐state DMN circuitry between healthy controls and children with TBI, (2) determine if severity of TBI was associated with differences in DMN connectivity and (3) evaluate whether patterns of DMN effective connectivity predicted persistent post‐concussion symptoms and anxiety. Healthy controls had unique positive connectivity that mostly emerged from the inferior temporal lobes. In contrast, children with TBI had unique effective connectivity among orbitofrontal and parietal regions. These positive orbitofrontal‐parietal DMN effective connectivity patterns also differed by TBI severity and were associated with persisting behavioural outcomes. Effective connectivity may be a sensitive neuroimaging marker of TBI severity as well as a predictor of chronic post‐concussion symptoms and anxiety.
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Abstract Mild traumatic brain injury (mTBI) is a frequently overlooked public health concern that is difficult to diagnose and treat. Diffuse axonal injury (DAI) is a common mTBI neuropathology in which axonal shearing and stretching induces breakdown of the cytoskeleton, impaired axonal trafficking, axonal degeneration, and cognitive dysfunction. DAI is becoming recognized as a principal neuropathology of mTBI with supporting evidence from animal model, human pathology, and neuroimaging studies. As mitochondrial dysfunction and calcium overload are critical steps in secondary brain and axonal injury, we investigated changes in protein expression of potential targets following mTBI using an in vivo controlled cortical impact model. We show upregulated expression of sodium calcium exchanger1 (NCX1) in the hippocampus and cortex at distinct time points post-mTBI. Expression of dynamin-related protein1 (Drp1), a GTPase responsible for regulation of mitochondrial fission, also changes differently post-injury in the hippocampus and cortex. Using an in vitro model of DAI previously reported by our group, we tested whether pharmacological inhibition of NCX1 by SN-6 and of dynamin1, dynamin2, and Drp1 by dynasore mitigates secondary damage. Dynasore and SN-6 attenuate stretch injury-induced swelling of axonal varicosities and mitochondrial fragmentation. In addition, we show that dynasore, but not SN-6, protects against H2O2-induced damage in an organotypic oxidative stress model. As there is currently no standard treatment to mitigate cell damage induced by mTBI and DAI, this work highlights two potential therapeutic targets for treatment of DAI in multiple models of mTBI and DAI.