Dataset Information

Resting-State fMRI Metrics in Acute Sport-Related Concussion and Their Association with Clinical Recovery: A Study from the NCAA-DOD CARE Consortium.

ABSTRACT: There has been a recent call for longitudinal cohort studies to track the physiological recovery of sport-related concussion (SRC) and its relationship with clinical recovery. Resting-state functional magnetic resonance imaging (rs-fMRI) has shown potential for detecting subtle changes in brain function after SRC. We investigated the effects of SRC on rs-fMRI metrics assessing local connectivity (regional homogeneity; REHO), global connectivity (average nodal strength), and the relative amplitude of slow oscillations of rs-fMRI (fractional amplitude of low-frequency fluctuations; fALFF). Athletes diagnosed with SRC (n?=?92) completed visits with neuroimaging at 24-48?h post-injury (24?h), after clearance to begin the return-to-play (RTP) progression (asymptomatic), and 7 days following unrestricted RTP (post-RTP). Non-injured athletes (n?=?82) completed visits yoked to the schedule of matched injured athletes and served as controls. Concussed athletes had elevated symptoms, worse neurocognitive performance, greater balance deficits, and elevated psychological symptoms at the 24-h visit relative to controls. These deficits were largely recovered by the asymptomatic visit. Concussed athletes still reported elevated psychological symptoms at the asymptomatic visit relative to controls. Concussed athletes also had elevated REHO in the right middle and superior frontal gyri at the 24-h visit that returned to normal levels by the asymptomatic visit. Additionally, REHO in these regions at 24?h predicted psychological symptoms at the asymptomatic visit in concussed athletes. Current results suggest that SRC is associated with an acute alteration in local connectivity that follows a similar time course as clinical recovery. Our results do not indicate strong evidence that concussion-related alterations in rs-fMRI persist beyond clinical recovery.

SUBMITTER: Meier TB

PROVIDER: S-EPMC6921290 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Resting-State fMRI Metrics in Acute Sport-Related Concussion and Their Association with Clinical Recovery: A Study from the NCAA-DOD CARE Consortium.

Meier Timothy B TB Giraldo-Chica Monica M España Lezlie Y LY Mayer Andrew R AR Harezlak Jaroslaw J Nencka Andrew S AS Wang Yang Y Koch Kevin M KM Wu Yu-Chien YC Saykin Andrew J AJ Giza Christopher C CC Goldman Joshua J DiFiori John P JP Guskiewicz Kevin M KM Mihalik Jason P JP Brooks Alison A Broglio Steven P SP McAllister Thomas T McCrea Michael A MA

Journal of neurotrauma 20190918 1

There has been a recent call for longitudinal cohort studies to track the physiological recovery of sport-related concussion (SRC) and its relationship with clinical recovery. Resting-state functional magnetic resonance imaging (rs-fMRI) has shown potential for detecting subtle changes in brain function after SRC. We investigated the effects of SRC on rs-fMRI metrics assessing local connectivity (regional homogeneity; REHO), global connectivity (average nodal strength), and the relative amplitud ...[more]

PMID: 31407610

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Project description:BACKGROUND:Concussion diagnosis is typically made through clinical examination and supported by performance on clinical assessment tools. Performance on commonly implemented and emerging assessment tools is known to vary between administrations, in the absence of concussion. OBJECTIVE:To evaluate the test-retest reliability of commonly implemented and emerging concussion assessment tools across a large nationally representative sample of student-athletes. METHODS:Participants (n = 4874) from the Concussion Assessment, Research, and Education Consortium completed annual baseline assessments on two or three occasions. Each assessment included measures of self-reported concussion symptoms, motor control, brief and extended neurocognitive function, reaction time, oculomotor/oculovestibular function, and quality of life. Consistency between years 1 and 2 and 1 and 3 were estimated using intraclass correlation coefficients or Kappa and effect sizes (Cohen's d). Clinical interpretation guidelines were also generated using confidence intervals to account for non-normally distributed data. RESULTS:Reliability for the self-reported concussion symptoms, motor control, and brief and extended neurocognitive assessments from year 1 to 2 ranged from 0.30 to 0.72 while effect sizes ranged from 0.01 to 0.28 (i.e., small). The reliability for these same measures ranged from 0.34 to 0.66 for the year 1-3 interval with effect sizes ranging from 0.05 to 0.42 (i.e., small to less than medium). The year 1-2 reliability for the reaction time, oculomotor/oculovestibular function, and quality-of-life measures ranged from 0.28 to 0.74 with effect sizes from 0.01 to 0.38 (i.e., small to less than medium effects). CONCLUSIONS:This investigation noted less than optimal reliability for most common and emerging concussion assessment tools. Despite this finding, their use is still necessitated by the absence of a gold standard diagnostic measure, with the ultimate goal of developing more refined and sound tools for clinical use. Clinical interpretation guidelines are provided for the clinician to apply with a degree of certainty in application.

Project description:Low image sampling rates used in resting state functional magnetic resonance imaging (rs-fMRI) may cause aliasing of the cardiorespiratory pulsations over the very low frequency (VLF) BOLD signal fluctuations which reflects to functional connectivity (FC). In this study, we examine the effect of sampling rate on currently used rs-fMRI FC metrics. Ultra-fast fMRI magnetic resonance encephalography (MREG) data, sampled with TR 0.1 s, was downsampled to different subsampled repetition times (sTR, range 0.3-3 s) for comparisons. Echo planar k-space sampling (TR 2.15 s) and interleaved slice collection schemes were also compared against the 3D single shot trajectory at 2.2 s sTR. The quantified connectivity metrics included stationary spatial, time, and frequency domains, as well as dynamic analyses. Time domain methods included analyses of seed-based functional connectivity, regional homogeneity (ReHo), coefficient of variation, and spatial domain group level probabilistic independent component analysis (ICA). In frequency domain analyses, we examined fractional and amplitude of low frequency fluctuations. Aliasing effects were spatially and spectrally analyzed by comparing VLF (0.01-0.1 Hz), respiratory (0.12-0.35 Hz) and cardiac power (0.9-1.3 Hz) FFT maps at different sTRs. Quasi-periodic pattern (QPP) of VLF events were analyzed for effects on dynamic FC methods. The results in conventional time and spatial domain analyses remained virtually unchanged by the different sampling rates. In frequency domain, the aliasing occurred mainly in higher sTR (1-2 s) where cardiac power aliases over respiratory power. The VLF power maps suffered minimally from increasing sTRs. Interleaved data reconstruction induced lower ReHo compared to 3D sampling (p < 0.001). Gradient recalled echo-planar imaging (EPI BOLD) data produced both better and worse metrics. In QPP analyses, the repeatability of the VLF pulse detection becomes linearly reduced with increasing sTR. In conclusion, the conventional resting state metrics (e.g., FC, ICA) were not markedly affected by different TRs (0.1-3 s). However, cardiorespiratory signals showed strongest aliasing in central brain regions in sTR 1-2 s. Pulsatile QPP and other dynamic analyses benefit linearly from short TR scanning.

Project description:Importance:There is potential scientific and clinical value in validation of objective biomarkers for sport-related concussion (SRC). Objective:To investigate the association of acute-phase blood biomarker levels with SRC in collegiate athletes. Design, Setting, and Participants:This multicenter, prospective, case-control study was conducted by the National Collegiate Athletic Association (NCAA) and the US Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium from February 20, 2015, to May 31, 2018, at 6 CARE Advanced Research Core sites. A total of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute postinjury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and 7 days after return to play. Data analysis was conducted from March 1 to November 30, 2019. Main Outcomes and Measures:Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain, and tau were quantified using the Quanterix Simoa multiplex assay. Clinical outcome measures included the Sport Concussion Assessment Tool-Third Edition (SCAT-3) symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, and Brief Symptom Inventory 18. Results:A total of 264 athletes with concussion (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] male), 138 contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] male), and 102 non-contact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] male) were included in the study. Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95% CI, 0.339-0.521 pg/mL; P < .001), UCH-L1 (mean difference, 0.449 pg/mL; 95% CI, 0.167-0.732 pg/mL; P < .001), and tau levels (mean difference, 0.221 pg/mL; 95% CI, 0.046-0.396 pg/mL; P = .004) at the acute postinjury time point compared with preseason baseline. Longitudinally, a significant interaction (group × visit) was found for GFAP (F7,1507.36 = 16.18, P < .001), UCH-L1 (F7,1153.09 = 5.71, P < .001), and tau (F7,1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F7,1506.90 = 1.33, P = .23). The area under the curve for the combination of GFAP and UCH-L1 in differentiating athletes with concussion from contact sport controls at the acute postinjury period was 0.71 (95% CI, 0.64-0.78; P < .001); the acute postinjury area under the curve for all 4 biomarkers combined was 0.72 (95% CI, 0.65-0.79; P < .001). Beyond SCAT-3 symptom score, GFAP at the acute postinjury time point was associated with the classification of athletes with concussion from contact controls (β = 12.298; 95% CI, 2.776-54.481; P = .001) and non-contact sport controls (β = 5.438; 95% CI, 1.676-17.645; P = .005). Athletes with concussion with loss of consciousness or posttraumatic amnesia had significantly higher levels of GFAP than athletes with concussion with neither loss of consciousness nor posttraumatic amnesia at the acute postinjury time point (mean difference, 0.583 pg/mL; 95% CI, 0.369-0.797 pg/mL; P < .001). Conclusions and Relevance:The results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in SRC.

Project description:Objectives: The objective of this study was to assess if injury-related alterations in the Sport Concussion Assessment Tool-5 (SCAT5) are matched by changes in transcranial magnetic stimulation-derived intracortical inhibition. We hypothesised that neurophysiological measures would take longer to return to normal than recovery assessed by the SCAT5 following sport related concussion (SRC). Methods: Thirteen male contact sport athletes (20.5 ± 4.5 years), who reported a concussion were recruited from local Rugby and American football clubs. Participants were tested at 4 timepoints throughout the concussion recovery period: within 24 h of concussion (day 0), and at 7, 9, and 11 days after concussion. All participants completed the SCAT5 and underwent TMS to assess cortical silent period duration (CSp), a measure of intracortical inhibition. Results: After concussion CSp significantly declined from day 0 (122 ± 28 ms) to day 11 (106 ± 15 ms) [F (3, 33) = 7.80, p < 0.001]. SCAT5 measures of symptom number and severity were significantly decreased [symptom number: χ(3)2 = 30.44, p < 0.01; symptom severity: χ(3)2 = 25.75, p < 0.001] between the day 0 timepoint and each of the other timepoints. SCAT5 balance errors (mBESS) decreased significantly [F (3, 33) = 19.55, p < 0.001] between the day 0 timepoint and each of the other timepoints. CSp and SCAT5 recovery patterns were different. SCAT5 domains recovered faster showing no further significant changes after day 7, whilst CSp was still decreasing between days 7 and 9. Due to the small sample size we also used a Bayesian linear model to investigate the recovery of CSp and mBESS. The posterior distribution of our Bayesian model provided evidence that CSp decreased at day 7 and it continued to decrease at day 9, unlike mBESS which decreased at day 7 and then reached a plateau. Conclusion: There are clinically important discrepancies between clinical and neurophysiological measures of concussion recovery. This finding has important implications for return to play (RTP) protocols and the prevention of complications after sport concussion.

Dataset Information

Resting-State fMRI Metrics in Acute Sport-Related Concussion and Their Association with Clinical Recovery: A Study from the NCAA-DOD CARE Consortium.

Publications

Resting-State fMRI Metrics in Acute Sport-Related Concussion and Their Association with Clinical Recovery: A Study from the NCAA-DOD CARE Consortium.

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