mTBI Group Research Articles

Slowing of Parameterized Resting-State Electroencephalography After Mild Traumatic Brain Injury.

Reported changes in electroencephalography (EEG)-derived spectral power after mild traumatic brain injury (mTBI) remains inconsistent across existing literature. However, this may be a result of previous analyses depending solely on observing spectral power within traditional canonical frequency bands rather than accounting for the aperiodic activity within the collected neural signal. Therefore, the aim of this study was to test for differences in rhythmic and arrhythmic time series across the brain, and in the cognitively relevant frontoparietal (FP) network, and observe whether those differences were associated with cognitive recovery post-mTBI. Resting-state electroencephalography (rs-EEG) was collected from 88 participants (56 mTBI and 32 age- and sex-matched healthy controls) within 14 days of injury for the mTBI participants. A battery of executive function (EF) tests was collected at the first session with follow-up metrics collected approximately 2 and 4 months after the initial visit. After spectral parameterization, a significant between-group difference in aperiodic-adjusted alpha center peak frequency within the FP network was observed, where a slowing of alpha peak frequency was found in the mTBI group in comparison to the healthy controls. This slowing of week 2 (collected within 2 weeks of injury) aperiodic-adjusted alpha center peak frequency within the FP network was associated with increased EF over time (evaluated using executive composite scores) post-mTBI. These findings suggest alpha center peak frequency within the FP network as a candidate prognostic marker of EF recovery and may inform clinical rehabilitative methods post-mTBI.

Mild Traumatic Brain Injuries and Risk for Affective and Behavioral Disorders.

Recent studies document an association between mild traumatic brain injuries (mTBIs) in children and postinjury psychiatric disorders. However. these studies were subject to limitations in the design, lack of long-term follow-up, and poorly defined psychiatric outcomes. This study determines the incidence and relative risk of postinjury new affective and behavior disorders 4 years after mTBIs. A cohort study of mTBI cases and matched comparisons within an integrated health care system. The mTBI group included patients ≤17 years of age, diagnosed with mTBI from 2000 to 2014 (N = 18 917). Comparisons included 2 unexposed patients (N = 37 834) per each mTBI-exposed patient, randomly selected and matched for age, sex, race/ethnicity, and date of medical visit (reference date to mTBI injury). Outcomes included a diagnosis of affective or behavioral disorders in the 4 years after mTBI or the reference date. Adjusted risks for affective disorders were significantly higher across the first 3 years after injury for the mTBI group, especially during the second year, with a 34% increase in risk. Adjusted risks for behavioral disorders were significant at years 2 and 4, with up to a 37% increase in risk. The age group with the highest risk for postinjury affective and behavioral disorders was 10- to 13-year-old patients. Sustaining an mTBI significantly increased the risks of having a new affective or behavioral disorder up to 4 years after injury. Initial and ongoing screening for affective and behavior disorders following an mTBI can identify persistent conditions that may pose barriers to recovery.

Investigating cognitive reserve, symptom resolution and brain connectivity in mild traumatic brain injury

BackgroundA proportion of patients with mild traumatic brain injury (mTBI) suffer long-term consequences, and the reasons behind this are still poorly understood. One factor that may affect outcomes is cognitive reserve, which is the brain's ability to maintain cognitive function despite injury. It is often assessed through educational level or premorbid IQ tests. This study aimed to explore whether there were differences in post-concussion symptoms and symptom resolution between patients with mTBI and minor orthopedic injuries one week and three months after injury. Additional aims were to explore the relationship between cognitive reserve and outcome, as well as functional connectivity according to resting state functional magnetic resonance imaging (rs-fMRI).MethodFifteen patients with mTBI and 15 controls with minor orthopedic injuries were recruited from the emergency department. Assessments, including Rivermead Post-Concussion Questionnaire (RPQ), neuropsychological testing, and rs-fMRI scans, were conducted on average 7 days (SD = 2) and 122 days (SD = 51) after injury.ResultsAt the first time point, significantly higher rates of post-concussion symptoms (U = 40.0, p = 0.003), state fatigue (U = 56.5, p = 0.014), and fatigability (U = 58.5, p = 0.025) were observed among the mTBI group than among the controls. However, after three months, only the difference in post-concussion symptoms remained significant (U = 27.0, p = 0.003). Improvement in post-concussion symptoms was found to be significantly correlated with cognitive reserve, but only in the mTBI group (Spearman’s rho = -0.579, p = .038). Differences in the trajectory of recovery were also observed for fatigability between the two groups (U = 36.5, p = 0.015). Moreover, functional connectivity differences in the frontoparietal network were observed between the groups, and for mTBI patients, functional connectivity differences in an executive control network were observed over time.ConclusionThe findings of this pilot study suggest that mTBI, compared to minor orthopedic trauma, is associated to both functional connectivity changes in the brain and concussion-related symptoms. While there is improvement in these symptoms over time, a small subgroup with lower cognitive reserve appears to experience more persistent and possibly worsening symptoms over time. This, however, needs to be validated in larger studies.Trial registrationNCT05593172. Retrospectively registered.

Long-term effects of multiple concussions on prefrontal cortex oxygenation during a hypercapnic challenge in retired contact sport athletes

This exploratory study aimed to investigate the long-term effects of multiple concussions on prefrontal cortex oxygenation during a five-minute hypercapnic challenge using Near Infrared Spectroscopy (NIRS). 55 physically active retired contact sport male athletes with three or more previous concussions (mTBI) were recruited along with 29 physically active males with no concussions history (CTRL). Participants completed five minutes of seated rest prior to the five-minute hypercapnic challenge (20-second breath-hold, 40-second recovery breathing; five times). NIRS measured right and left side oxygenated (O2Hb), deoxygenated (HHb), total (tHb) haemoglobin, and haemoglobin difference (HbDiff) with all parameters analysed through changes in average maximal and minimal values (ΔMAX), Z-scores, and standard deviations. Right prefrontal cortex HbDiff ΔMAX was significantly higher in the mTBI compared to CTRL (p = 0.045) group. Left prefrontal cortex O2Hb ΔMAX (p = 0.040), HHb Z-Scores (p = 0.008), and HbDiff ΔMAX(p = 0.014) were significantly higher in the mTBI group. Within-group right vs left analyses demonstrated significantly lower left HbDiff ΔMAX (p = 0.048) and HbDiff Z-scores (p = 0.002) in the mTBI group, while the CTRL group had significantly lower left HHb Z-scores (p = 0.003) and left tHb Z-scores (p = 0.042). This study provides preliminary evidence that athletes with a history of three or more concussions may have impaired prefrontal cortex oxygenation parameters during a hypercapnic challenge.

Assessing the Effects of Mild Traumatic Brain Injury on Vestibular Home Exercise Performance with Wearable Sensors.

After a mild traumatic brain injury (mTBI), dizziness and balance problems are frequently reported, affecting individuals' daily lives and functioning. Vestibular rehabilitation is a standard treatment approach for addressing these issues, but its efficacy in this population remains inconclusive. A potential reason for suboptimal outcomes is the lack of objective monitoring of exercise performance, which is crucial for therapeutic success. This study utilized wearable inertial measurement units (IMUs) to quantify exercise performance in individuals with mTBI during home-based vestibular rehabilitation exercises. Seventy-three people with mTBI and fifty healthy controls were enrolled. Vestibular exercises were performed, and IMUs measured forehead and sternum velocities and range of motions. The mTBI group demonstrated a slower forehead peak angular velocity in all exercises, which may be a compensatory strategy to manage balance issues or symptom exacerbation. Additionally, the mTBI group exhibited a larger forehead range of motion during specific exercises, potentially linked to proprioceptive deficits. These findings emphasize the usefulness of utilizing IMUs to monitor the quality of home-based vestibular exercises for individuals with mTBI and the potential for IMUs improving rehabilitation outcomes.

Brain functional connectivity in children with a mild traumatic brain injury: A scoping review

Introduction The occurrence of mild traumatic brain injury(mTBI) is estimated at 0,2-0,3% cases annually. Following a mTBI, some children experience persistent symptoms, and functional connectivity(FC) changes may be implicated. However, characteristics of FC have not been widely described in this population. This scoping review aimed to identify and understand the impacts of mTBI on EEG-measured FC in children, provide an overview of the available literature, detail analysis techniques, and describe gaps in the research. Methods PubMed, Web of Science, Medline, Embase, ProQuest and CINAHL were searched up to June 25, 2023, with the terms child, mTBI, EEG, FC, and their synonyms. Ten studies were identified. Results Five studies reported significant differences between the mTBI group and controls. In addition to group differences, six studies reported significant variation over time. Brain Network Analysis(BNA), utilized in seven studies, was the primary FC analysis recorded. Two of the five studies that reported significant differences following mTBI utilized the BNA. The other three applied alternative analysis methods. Discussion FC assessment based on EEG can identify some differences in children with mTBI. BNA was more useful in following changes over time. Further research is suggested, considering the limited age range and number of retrieved studies.

The Influence of Prior Head Injury on Late‐Life Cognition and White Matter Microstructure in Older Adults At‐Risk of Alzheimer’s disease

AbstractBackgroundThe long‐term combined effects of mild traumatic brain injury (mTBI) and APOE ε4‐allele carrier status (APOE+/‐), a genetic risk factor of Alzheimer’s disease (AD), on cognition and white matter structural integrity in older adults at‐risk of AD is not fully understood.MethodTo investigate mTBI effects on late‐life neurobehavioural outcomes, a subsample of the PREVENT‐AD cohort was analyzed. Participants were cognitively normal adults over age 55 with a parental or multiple‐sibling history of AD. The mTBI group included individuals who self‐reported at least one prior mTBI with loss of consciousness and/or memory gap (n = 48, 33.3% APOE4+). Rey Auditory Verbal Learning Test measured immediate and delayed memory, Color‐Word Interference Test measured cognitive flexibility and inhibitory control, and Trail Making Test measured processing speed and attention.The control group included demographically‐matched (age, sex, years of education) participants from the same cohort without self‐reported mTBI (n = 62, 29.0% APOE4+). Data were analyzed using 2‐way ANOVAs with weighted means on years of education, corrected for multiple comparisons. To evaluate underlying structural differences in white matter tracts between mTBI and control groups, diffusion tensor imaging (DTI) metrics, including fractional anisotropy, axial and radial diffusivity, using the JHU‐atlas parcellation.ResultsmTBI/APOE4+ individuals performed significantly worse on cognitive outcomes of delayed recall, cognitive flexibility, and inhibitory control compared to controls; however, they performed significantly better on tests of processing speed and visual attention compared to mTBI/APOE4‐ individuals. DTI results showed that the mTBI group, compared to the control group, had significantly decreased axial diffusivity in the left internal capsule, right superior longitudinal fasciculus, and superior frontooccipital fasciculus (SFOF) (p<0.05 uncorrected). Within the mTBI group, significant positive correlation between lower processing speed and decreased axial diffusivity of SFOF, accounting for age and sex.ConclusionOur findings suggest that prior mTBI impacts cognitive aging in older adults at‐risk of AD differentially depend on APOE4 status, where APOE4+ individuals with prior mTBI had worse working memory, cognitive flexibility, and inhibitory control but better processing speed outcomes. Lower cognitive outcomes in mTBI individuals may be supported by decreased diffusivity in specific white matter tracts. These results can inform dementia prevention in these individuals.

The Influence of Prior Head Injury on Late‐Life Cognition and White Matter Microstructure in Older Adults At‐Risk of Alzheimer’s disease

AbstractBackgroundThe long‐term combined effects of mild traumatic brain injury (mTBI) and APOE e4‐allele carrier status (APOE+/‐), a genetic risk factor of Alzheimer’s disease (AD), on cognition and white matter structural integrity in older adults at‐risk of AD is not fully understood.MethodTo investigate mTBI effects on late‐life neurobehavioural outcomes, a subsample of the PREVENT‐AD cohort was analyzed. Participants were cognitively normal adults over age 55 with a parental or multiple‐sibling history of AD. The mTBI group included individuals who self‐reported at least one prior mTBI with loss of consciousness and/or memory gap (n = 48, 33.3% APOE4+). Rey Auditory Verbal Learning Test measured immediate and delayed memory, Color‐Word Interference Test measured cognitive flexibility and inhibitory control, and Trail Making Test measured processing speed and attention. The control group included demographically‐matched (age, sex, years of education) participants from the same cohort without self‐reported mTBI (n = 62, 29.0% APOE4+). Data were analyzed using 2‐way ANOVAs with weighted means on years of education, corrected for multiple comparisons. To evaluate underlying structural differences in white matter tracts between mTBI and control groups, diffusion tensor imaging (DTI) metrics, including fractional anisotropy, axial and radial diffusivity, using the JHU‐atlas parcellation.ResultmTBI/APOE4+ individuals performed significantly worse on cognitive outcomes of delayed recall, cognitive flexibility, and inhibitory control compared to controls; however, they performed significantly better on tests of processing speed and visual attention compared to mTBI/APOE4‐ individuals. DTI results showed that the mTBI group, compared to the control group, had significantly decreased axial diffusivity in the left internal capsule, right superior longitudinal fasciculus, and superior frontooccipital fasciculus (SFOF) (p<0.05 uncorrected). Within the mTBI group, significant positive correlation between lower processing speed and decreased axial diffusivity of SFOF, accounting for age and sex.ConclusionOur findings suggest that prior mTBI impacts cognitive aging in older adults at‐risk of AD differentially depend on APOE4 status, where APOE4+ individuals with prior mTBI had worse working memory, cognitive flexibility, and inhibitory control but better processing speed outcomes. Lower cognitive outcomes in mTBI individuals may be supported by decreased diffusivity in specific white matter tracts. These results can inform dementia prevention in these individuals.

CSF Alzheimer’s Disease Biomarker Changes in Veterans with Mild Traumatic Brain Injury

AbstractBackgroundTraumatic brain injury (TBI) has been reported to increase risk of Alzheimer’s dementia (AD). It remains unknown whether mild TBI (mTBI) caused by blast in Veterans confers a similar increase of risk. This study investigated early AD changes defined by cerebrospinal fluid (CSF) AD biomarkers in Veterans with blast mTBI.MethodFifty‐one Veterans with mTBI, 34 non‐mTBI Veterans, and 51 non‐mTBI civilians were recruited from Seattle, Washington. Age‐matched Veteran and civilian non‐mTBI participants had no lifetime history of TBI. All blast‐mTBI Veterans had experienced at least one war zone blast or combined blast/impact exposure, with acute symptoms meeting VA/Department of Defense criteria for mTBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of CSF. CSF biomarkers were measured at the Clinical Neurochemistry Lab in Mölndal, Sweden, using Meso Scale Discovery (MSD) assays for Aβ40 and Aβ42, and Innotest ELISAs for phosphorylated Tau181 (pTau181) and total Tau (tTau).ResultDifferences in all 4 CSF AD biomarkers between participants with and without mTBI were highly age‐dependent and most pronounced in older ages (Figure 1). Both CSF Aβ40 and Aβ42 became lower as age increasing in the mTBI group starting around age 40‐45 years, while they increased with age in the non‐mTBI participants. In contrast, CSF tTau and pTau181 mean levels remained relatively constant with age in participants with mTBI, but increased after age 45 in the non‐mTBI participants. Consequently, for participants aged 50+ years, Veterans with mTBI had lower mean AD biomarkers than the non‐mTBI participants. Similarly, the differences in cognitive performance were age‐dependent, i.e., poorer performance in older Veterans with mTBI than in the non‐mTBI participants. Furthermore, the relationships between CSF Aβ42 and cognitive performance were also age‐dependent; specifically, in participants aged 45+ years, lower CSF Aβ42 level was associated with poorer performance on tests of verbal fluency and memory.ConclusionThe earliest AD biomarker, CSF Aβ42, started to decrease in middle‐aged Veterans with mTBI, more than a decade earlier than those without mTBI in our earlier study, suggesting mTBI may accelerate brain deposition of Aβ and increase risk for AD.

Late Blood Levels of Neurofilament Light Correlate With Outcome in Patients With Traumatic Brain Injury.

Neurofilament light (NF-L) is an axonal protein that has shown promise as a traumatic brain injury (TBI) biomarker. Serum NF-L shows a rather slow rise after injury, peaking after 1-2 weeks, although some studies suggest that it may remain elevated for months after TBI. The aim of this study was to examine if plasma NF-L levels several months after the injury correlate with functional outcome in patients who have sustained TBIs of variable initial severity. In this prospective study of 178 patients with TBI and 40 orthopedic injury controls, we measured plasma NF-L levels in blood samples taken at the follow-up appointment on average 9 months after injury. Patients with TBI were divided into two groups (mild [mTBI] vs. moderate-to-severe [mo/sTBI]) according to the severity of injury assessed with the Glasgow Coma Scale upon admission. Recovery and functional outcome were assessed using the Extended Glasgow Outcome Scale (GOSE). Higher levels of NF-L at the follow-up correlated with worse outcome in patients with moderate-to-severe TBI (Spearman's rho = -0.18; p < 0.001). In addition, in computed tomography-positive mTBI group, the levels of NF-L were significantly lower in patients with GOSE 7-8 (median 18.14; interquartile range [IQR] 9.82, 32.15) when compared with patients with GOSE <7 (median 73.87; IQR 32.17, 110.54; p = 0.002). In patients with mTBI, late NF-L levels do not seem to provide clinical benefit for late-stage assessment, but in patients with initially mo/sTBI, persistently elevated NF-L levels are associated with worse outcome after TBI and may reflect ongoing brain injury.

Telomere Length Associates With Symptom Severity After Mild Traumatic Brain Injury in Older Adults.

The objectives were to compare differences in telomere length (TL) among younger (21-54 years) and older adults (≥55) with mild traumatic brain injury (mTBI) to non-injured controls and to examine the association between TL and the severity of post-concussive symptoms over time. We performed a quantitative polymerase chain reaction to determine the TL (Kb/genome) of peripheral blood mononuclear cell samples (day 0, 3 months, and 6 months) from 31 subjects. The Rivermead Post-Concussion Symptoms Questionnaire was used to assess symptoms. Group-by-time comparisons of TL and symptom severity were evaluated with repeated-measures analysis of variance. Multiple linear regression examined the relationship between TL, group (mTBI and non-injured controls), and symptom severity total and subscale scores. Significant aging-related differences in TL were found within mTBI groups by time (day 0, 3 months, and 6 months; p = 0.025). Older adults with mTBI experienced significant worsening of changes in total symptom severity scores over time (day 0, 3 months, and 6 months; p = 0.016). Shorter TLs were associated with higher total symptom burden among each of the four groups at day 0 (baseline; p = 0.035) and 3 months (p = 0.038). Shorter TL was also associated with higher cognitive symptom burden among the four groups at day 0 (p = 0.008) and 3 months (p = 0.008). Shorter TL was associated with higher post-injury symptom burden to 3 months in both older and younger persons with mTBI. Large-scale, longitudinal studies of factors associated with TL may be useful to delineate the mechanistic underpinnings of higher symptom burden in adults with mTBI.

Correlation of Insulin-Like Growth Factor 1 With Cognitive Functions in Mild Traumatic Brain Injury Patients.

Mild traumatic brain injury (mTBI) is a prevalent health concern with variable recovery trajectories, necessitating reliable prognostic markers. Insulin-like growth factor 1 (IGF-1) emerges as a potential candidate because of its role in cellular growth, repair, and neuroprotection. However, limited studies investigate IGF-1 as a prognostic marker in mTBI patients. This study aimed to explore the correlation of IGF-1 with cognitive functions assessed using the Wisconsin Card Sorting Test (WCST) in mTBI patients. We analyzed data from 295 mTBI and 200 healthy control participants, assessing demographic characteristics, injury causes, and IGF-1 levels. Cognitive functions were evaluated using the WCST. Correlation analyses and regression models were used to investigate the associations between IGF-1 levels, demographic factors, and WCST scores. Significant differences were observed between mTBI and control groups in the proportion of females and average education years. Falls and traffic accidents were identified as the primary causes of mTBI. The mTBI group demonstrated worse cognitive outcomes on the WCST, except for the "Learning to Learn" index. Correlation analyses revealed significant relationships between IGF-1 levels, demographic factors, and specific WCST scores. Regression models demonstrated that IGF-1, age, and education years significantly influenced various WCST scores, suggesting their roles as potential prognostic markers for cognitive outcomes in mTBI patients. We provide valuable insights into the potential correlation of IGF-1 with cognitive functions in mTBI patients, particularly in tasks requiring cognitive flexibility and problem solving.

49 Longitudinal White Matter Changes in First Time Mild Traumatic Brain Injury in Relationship with Cognitive Performance: A Diffusion Tensor Imaging Study

Objective:The objective of the study was to examine longitudinal changes in the white matter tracts with diffusion tensor imaging (DTI), neuropsychological performance, and the associate between the two in adults with a mild traumatic brain injury (mTBI).Participants and Methods:Sixteen adult patients (age = 38.5(12.8); 75% female) seeking medical care at an emergency department for their first mTBI and 15 healthy adults (age = 30.5(11.3); 33% female) from the community were recruited. DTI and the neuropsychological evaluation were performed at 7 days and 4-months post-injury. The neuropsychological evaluation consisted of the CNS Vital Signs computerized neurocognitive test battery and 2 trials of the Paced Auditory Serial-Addition Test.Results:Results showed a significant decrease in fractional anisotropy (FA) and an increase in radial diffusivity (RD) of the right uncinate fasciculus as well as a significant decrease in FA and axial diffusivity (AD) of the right inferior fronto-occipital fasciculus over the 4-month follow-up period in the mTBI group compared to the Control group.The FA of multiple white matter tracts at baseline were positively associated with working memory, sustained attention, and complex attention at baseline in the mTBI group but not the Control group. The global mean cerebral diffusivity for FA at baseline was positively associated with working memory and sustained attention at 4-months post-injury.Conclusions:The current findings of abnormal white matter suggest an oxidative stress reaction as a result of mTBI altering the diffusivity of some white matter tracts. Furthermore, the disruption of the white matter tracts at baseline may serve as a biomarker for identifying mTBI and those who may have prolonged cognitive difficulties in working memory and attention as a result of the mTBI.

74 Timed Motor Performance in Children Medically Cleared for Return to Activities Post Mild Traumatic Brain Injury

Objective:Children who sustain a mild traumatic brain injury (mTBI) are at increased odds of additive injury and continue to show altered motor performance relative to never-injured peers after being medically cleared (MC) to return to normal activities. There is a critical need to determine when children can return to activities without risk of short and long-term adverse effects, with research showing high reinjury rates for 3-12 months after RTP. The Physical and Neurological Examination for Subtle Signs (PANESS) measures subtle signs of motor impairment during gait, balance, and timed motor functions. Recent literature has demonstrated that PANESS timed motor function can distinguish between children medically cleared post-mTBI compared to never-injured controls. The present study examined performance on timed motor tasks in youth medically cleared from mTBI following medical clearance and 3-months later, compared to never-injured peers.Participants and Methods:25 children (Mage=14.16, SD=2.46; Male=68%) were enrolled within 6 weeks of medical clearance from mTBI (Mdays post MC=33, SD=13.4, Range=2-59) along with 66 typically developing, never-injured controls (Mage=13.9, SD=2.22; Male=50%). Group differences were evaluated for the Timed Motor section of the PANESS at enrollment and at a 3-month follow-up (Mdays from enrollment to follow-up=95.90, SD=12.69, Range=62-129). This 3-month follow-up occurred on average 4 months after medical clearance (Mdays from MC to follow-up=130.08, SD=17.58, Range=92 - 164). The Timed Motor section includes Repetitive (foot tapping, hand patting, and finger tapping) and Sequential (heel-toe rocking, hand pronate/supinate, finger sequencing) raw time scores, measured in seconds. The Total Timed Motor Speed score is the combination of Repetitive and Sequential Movement and the side-to-side tongue item.Results:At 3-month follow-up, mTBI participants (M=67.55, SD=8.26, Range=53.66-83.88) performed worse than controls (M=63.09, SD=10.23, Range=39.86-100.51) on Total Timed Motor Speed, t(89)= 1.95, p&lt;0.05), including when controlling for age and sex, F(1, 87)=4.67, p&lt;0.05. At the same time point, mTBI participants (M=36.54, SD=5.47, Range=28.74-49.17) performed worse on Sequential Speed than controls (M=32.93, SD=6.1, Range=21.49-56.76), t(89)=2.59, p&lt;0.01, including when controlling for age and sex, F(1, 87)=7.687, p&lt;0.01). Although groups performed similarly on Sequential Speed at the initial time point, mTBI participants exhibited a trend of less improvement from initial to follow-up (MmTBI=-1.69, Mcontrol=-3.68, t(90)=1.445, p=0.076).Conclusions:Although groups did not significantly differ on Timed Motor Speed items at the initial time point, the mTBI group showed consistently lower scores than controls at both time points and less improvement over time. Results indicate that Total Timed Motor Speed, specifically Sequential Speed, may be a sensitive marker of persisting differences in high-level motor and cognitive learning/control in children who have been medically cleared after mTBI. More data are needed to evaluate these findings over a longer time period, and future studies should examine behavioral markers concurrently with physiologic brain recovery over time.

Dynamic Relations Between Psychological Resilience and Post-Concussion Symptoms in Children With Mild Traumatic Brain Injury Versus Orthopedic Injury: An A-CAP Study.

Higher psychological resilience is correlated with less severe post-concussion symptoms (PCS) after mild traumatic brain injury (mTBI) in children, but the directional nature of this relationship remains uncertain. Although traditionally regarded as a stable, trait-like construct, resilience may be malleable and potentially influenced by mTBI and post-concussive symptoms. The current study sought to examine the stability of resilience, elucidate the dynamic nature of the resilience-PCS relation, and determine whether resilience-symptom associations are specific to mTBI or applicable to traumatic injury in general. Participants were children aged 8-16.99 years with either mTBI (n = 633) or orthopedic injury (OI; n = 334) recruited to participate in a prospective cohort study after presenting acutely to five Canadian pediatric emergency departments (EDs). Symptoms and psychological resilience were assessed at 1 week, 3 months, and 6 months post-injury. Group differences in resilience over time were examined using a mixed linear model, and associations between resilience and symptoms over time were examined using random intercepts cross-lagged panel modeling (RI-CLPM). The mTBI group reported significantly lower resilience than the OI group, but the difference was significantly larger 1 week post-injury (d = 0.50) than at 3 months (d = 0.08) and 6 months (d = 0.10). Cross-lagged panel models indicated that resilience had both stable and dynamic aspects, and both affected and was affected by PCS, although their association varied by time post-injury, symptom measure, and reporter (parent vs. child). Higher parent-reported cognitive symptom severity at 1 week was significantly associated with higher resilience at 3 months (β = 0.23, p = 0.001). Higher resilience at 3 months was associated with lower levels of parent-reported somatic symptom severity (β = -0.14, p = 0.004) and fewer total symptoms (β = -0.135, p = 0.029) at 6 months. Higher resilience at 3 months was associated with fewer child-reported symptoms at 6 months (β = -0.11, p = 0.030) and, reciprocally, fewer child-reported symptoms at 3 months were associated with higher resilience at 6 months (β = -0.22, p = 0.001). Notably, injury group was not a significant moderator in cross-lagged models, suggesting that resilience-symptom associations are not specific to mTBI. Psychological resilience and symptoms have bidirectional relationships after injury. Interventions designed to foster resilience have the potential to promote recovery after mTBI specifically and injury more generally.

The relationship between cognition and white matter tract damage after mild traumatic brain injury in a premorbidly healthy, hospitalised adult cohort during the post-acute period

IntroductionRecent developments in neuroimaging techniques enable increasingly sensitive consideration of the cognitive impact of damage to white matter tract (WMT) microstructural organisation after mild traumatic brain injury (mTBI).ObjectiveThis study investigated the relationship between WMT microstructural properties and cognitive performance.Participants, setting and designUsing an observational design, a group of 26 premorbidly healthy adults with mTBI and a group of 20 premorbidly healthy trauma control (TC) participants who were well-matched on age, sex, premorbid functioning and a range of physical, psychological and trauma-related variables, were recruited following hospital admission for traumatic injury.Main measuresAll participants underwent comprehensive unblinded neuropsychological examination and structural neuroimaging as outpatients 6–10 weeks after injury. Neuropsychological examination included measures of speed of processing, attention, memory, executive function, affective state, pain, fatigue and self-reported outcome. The WMT microstructural properties were estimated using both diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) modelling techniques. Tract properties were compared between the corpus callosum, inferior longitudinal fasciculus, uncinate fasciculus, anterior corona radiata and three segmented sections of the superior longitudinal fasciculus.ResultsFor the TC group, in all investigated tracts, with the exception of the uncinate fasciculus, two DTI metrics (fractional anisotropy and apparent diffusion coefficient) and one NODDI metric (intra-cellular volume fraction) revealed expected predictive linear relationships between extent of WMT microstructural organisation and processing speed, memory and executive function. The mTBI group showed a strikingly different pattern relative to the TC group, with no relationships evident between WMT microstructural organisation and cognition on most tracts.ConclusionThese findings indicate that the predictive relationship that normally exists in adults between WMT microstructural organisation and cognition, is significantly disrupted 6–10 weeks after mTBI and suggests that WMT microstructural organisation and cognitive function have disparate recovery trajectories.

Distance horizontal fusional facility (DFF): A new diagnostic vergence test for the acquired brain injury (ABI) population

PurposeTo report the retrospectively-based, clinical diagnostic findings for the horizontal, distance, fusional facility (DFF) test in the non-TBI (traumatic brain inury), ABI (acquired brain injury) population. MethodsThe DFF test (4 pd base-out/2 pd base-in) was assessed and compared retrospectively in the first author's optometric practice in three clinical populations: (1) post-mTBI, visually-symptomatic (n = 52), (2) post-ABI, non-mTBI, visually-symptomatic (n = 34), and (3) visually-normal, visually asymptomatic (n = 44). ResultsThe DFF values in each group were significantly different from each other (p < 0.05). The mean non-TBI, ABI group value was significantly lower than found in the mTBI group, and both were significantly lower than the mean found in the normal cohort (p < 0.05). There was a significant reduction in DFF with increased age (p < 0.001). ROC values for the AUC ranged from excellent to acceptable (0.94–0.74). ConclusionThe DFF test is a new and useful way to assess horizontal, distance, dynamic, fusional facility in those with presumed non-mTBI, ABI neurological conditions to assist in its diagnosis.

Whole-Blood Metabolomics of a Rat Model of Repetitive Concussion.

Mild traumatic brain injury (mTBI) and repetitive mTBI (RmTBI) are silent epidemics, and so far, there is no objective diagnosis. The severity of the injury is solely based on the Glasgow Coma Score (GCS) scale. Most patients suffer from one or more behavioral abnormalities, such as headache, amnesia, cognitive decline, disturbed sleep pattern, anxiety, depression, and vision abnormalities. Additionally, most neuroimaging modalities are insensitive to capture structural and functional alterations in the brain, leading to inefficient patient management. Metabolomics is one of the established omics technologies to identify metabolic alterations, mostly in biofluids. NMR-based metabolomics provides quantitative metabolic information with non-destructive and minimal sample preparation. We employed whole-blood NMR analysis to identify metabolic markers using a high-field NMR spectrometer (800MHz). Our approach involves chemical-free sample pretreatment and minimal sample preparation to obtain a robust whole-blood metabolic profile from a rat model of concussion. A single head injury was given to the mTBI group, and three head injuries to the RmTBI group. We found significant alterations in blood metabolites in both mTBI and RmTBI groups compared with the control, such as alanine, branched amino acid (BAA), adenosine diphosphate/adenosine try phosphate (ADP/ATP), creatine, glucose, pyruvate, and glycerphosphocholine (GPC). Choline was significantly altered only in the mTBI group and formate in the RmTBI group compared with the control. These metabolites corroborate previous findings in clinical and preclinical cohorts. Comprehensive whole-blood metabolomics can provide a robust metabolic marker for more accurate diagnosis and treatment intervention for a disease population.

Evaluation of Brain Rotational Injury Criteria (BrIC) in vehicle frontal crashes

Objective The objective of this study was to estimate strains in the human brain in regulatory, research, and due care frontal crashes by simulating those impacts. In addition, brain strain simulations were estimated for belted human volunteer tests and in impacts between two players in National Football League (NFL), some with no injury and some with mild Traumatic Brain Injuries (mTBI). Methods The brain strain responses were determined using version 5 of the Global Human Body Modeling Consortium (GHBMC) 50th percentile human brain model. One hundred and sixty simulations with the brain model were conducted using rotational velocities and accelerations of Anthropomorphic Test Devices (ATD’s) or those of human volunteers in sled or crash tests, as inputs to the model and strain related responses like Maximum Principal Strains (MPS) and Cumulative Strain Damage Measure (CSDM) in various regions of the brain were monitored. The simulated vehicle tests ranged from sled tests at 24 and 32 kph delta-V with three-point belts without airbags to full scale crash and sled tests at 56 kph and a series of Research Mobile Deformable Barrier (RMDB) tests described in Prasad et al. Results The severity of rotational input into the model as represented by BrIC, averaged between 0.5 and 1.2 for the various test conditions, and as high as 1.5 for an individual case. The MPS responses for the various test conditions averaged between 0.28 and 0.86 and as high as 1.3 in one test condition. The MPS responses in the brain for volunteers, low velocity sled, and NCAP tests were similar to those in the no-mTBI group in the NFL cases and consistent with real world accident data. The MPS responses of the brain in angular crash and sled tests were similar to those in the mTBI group. Conclusions The brain strain estimations do not indicate the likelihood of severe-to-fatal brain injuries in the crash environments studied in this paper. However, using the risk functions associated with BrIC, severe-to-fatal brain injuries (AIS4+) are predicted in several environments in which they are not observed or expected.

Adverse Outcome Following Mild Traumatic Brain Injury Is Associated with Microstructure Alterations at the Gray and White Matter Boundary.

The gray matter/white matter (GM/WM) boundary of the brain is vulnerable to shear strain associated with mild traumatic brain injury (mTBI). It is, however, unknown whether GM/WM microstructure is associated with long-term outcomes following mTBI. The diffusion and structural MRI data of 278 participants between 18 and 65 years of age with and without military background from the Department of Defense INTRuST study were analyzed. Fractional anisotropy (FA) was extracted at the GM/WM boundary across the brain and for each lobe. Additionally, two conventional analytic approaches were used: whole-brain deep WM FA (TBSS) and whole-brain cortical thickness (FreeSurfer). ANCOVAs were applied to assess differences between the mTBI cohort (n = 147) and the comparison cohort (n = 131). Associations between imaging features and post-concussive symptom severity, and functional and cognitive impairment were investigated using partial correlations while controlling for mental health comorbidities that are particularly common among military cohorts and were present in both the mTBI and comparison group. Findings revealed significantly lower whole-brain and lobe-specific GM/WM boundary FA (p < 0.011), and deep WM FA (p = 0.001) in the mTBI cohort. Whole-brain and lobe-specific GM/WM boundary FA was significantly negatively correlated with post-concussive symptoms (p < 0.039), functional (p < 0.016), and cognitive impairment (p < 0.049). Deep WM FA was associated with functional impairment (p = 0.002). Finally, no significant difference was observed in cortical thickness, nor between cortical thickness and outcome (p > 0.05). Findings from this study suggest that microstructural alterations at the GM/WM boundary may be sensitive markers of adverse long-term outcomes following mTBI.