A Multimodal Exertional Test for concussion: a pilot study in healthy athletes.

Introduction: Exertional tests have become a promising tool to assist clinicians in the management of concussions, however require expensive equipment, extensive spaces, and specialized clinician expertise. As such, we developed a test with minimal resource requirements encompassing key elements of sport and physical activity. The purpose of this study was to pilot test the Multimodal Exertional Test (MET) protocol in a sample of healthy interuniversity athletes. Methods: The MET comprises four stages, each featuring three distinct tasks. The test begins with engaging in squats, alternating reverse lunges, and hip hinges (Stage 1). The next stage progressively evolves into executing these tasks within specified time limits (Stage 2). Following this, the test advances to a stage that incorporates cognitive tasks (Stage 3), and the final stage demands greater levels of physical exertion, cognition, and multi-directional movements (Stage 4). Heart rate (HR) was obtained during each stage of the MET and participants' symptom severity scores were recorded following each task. Results: Fourteen healthy interuniversity athletes (n = 8 female, n = 6 male) participated in the study. HR was obtained for 10 of the 14 athletes (females: n = 6, males: n = 4). Increases in average and maximum HR were identified between pre-MET and Stage 1, and between Stages 3 and 4. Consistent with the tasks in each stage, there were no increases in average and maximum HR observed between MET Stages 1 to 3. Female athletes exhibited higher average and maximum HRs compared to male athletes during all four stages. All 14 athletes reported minimal changes in symptom severity following each task. Conclusion: Among healthy athletes, the MET elicits an increase in average and maximum HR throughout the protocol without symptom provocation. Female athletes exhibit higher HRs during all four stages in comparison to male athletes.

Whole blood stimulation provides preliminary evidence of altered immune function following SRC.

PURPOSE: To implement an approach combining whole blood immune stimulation and causal modelling to estimate the impact of sport-related concussion (SRC) on immune function. METHODS: A prospective, observational cohort study was conducted on athletes participating across 13 university sports at a single academic institute; blood was drawn from 52 athletes, comprised of 22 athletes (n = 11 male, n = 11 female) within seven days of a physician-diagnosed SRC, and 30 healthy athletes (n = 18 female, n = 12 male) at the beginning of their competitive season. Blood samples were stimulated for 24 h under two conditions: (1) lipopolysaccharide (lps, 100ng/mL) or (2) resiquimod (R848, 1uM) using the TruCulture® system. The concentration of 45 cytokines and chemokines were quantitated in stimulated samples by immunoassay using the highly sensitive targeted Proximity Extension Assays (PEA) on the Olink® biomarker platform. A directed acyclic graph (DAG) was used as a heuristic model to make explicit scientific assumptions regarding the effect of SRC on immune function. A latent factor analysis was used to derive two latent cytokine variables representing immune function in response to LPS and R848 stimulation, respectively. The latent variables were then modelled using student-t regressions to estimate the total causal effect of SRC on immune function. RESULTS: There was an effect of SRC on immune function in males following SRC, and it varied according to prior concussion history. In males with no history of concussion, those with an acute SRC had lower LPS reactivity compared to healthy athletes with 93% posterior probability (pprob), and lower R848 reactivity with 77% pprob. Conversely, in males with a history of SRC, those with an acute SRC had higher LPS reactivity compared to healthy athletes with 85% pprob and higher R848 reactivity with 82%. In females, irrespective of concussion history, SRC had no effect on LPS reactivity. However, in females with no concussion history, those with an acute SRC had higher R848 reactivity compared to healthy athletes with 86% pprob. CONCLUSION: Whole blood stimulation can be used within a causal framework to estimate the effect of SRC on immune function. Preliminary evidence suggests that SRC affects LPS and R848 immunoreactivity, that the effect is stronger in male athletes, and differs based on concussion history. Replication of this study in a larger cohort with a more sophisticated causal model is necessary.

Concussion Characteristics in the National Hockey League Before and After the Introduction of Rule 48.

Importance: A rule prohibiting a direct hit to the lateral side of the head (ie, Rule 48-Illegal Check to the Head) was introduced in the National Hockey League (NHL) in the 2010-2011 season and refined in the 2011-2012 season to widen the application to include direct contact to all areas of the head. Objective: To compare the incidence and proportion of concussions that occurred following hits to the head before and after the implementation of Rule 48. Design, Setting, and Participants: This retrospective cohort study used a before and after design to evaluate concussions among NHL players in regular season games. Data from the 4 seasons preceding the implementation of Rule 48 (2006-2007 to 2009-2010) were compared with data from 5 seasons following its implementation (2014-2015 to 2018-2019). Data were analyzed from October 31, 2021, to November 30, 2022. Main Outcomes and Measures: The incidence and relative proportion of concussion characteristics and mechanisms before and after the introduction of Rule 48. Results: In the analysis of 688 concussions for NHL seasons spanning 2006 to 2010 (n = 231) and 2014 to 2019 (n = 457), there was an overall increase in the incidence of concussion between the 2 time frames, although the incidence of concussions due to hits to the lateral aspect of the head decreased from 1.6/100 games to 1.0/100 games (estimated difference, 0.6/100 games [90% credible interval (CrI), 0.30/100 games to 0.90/100 games). There was also a reduction of 18.8 (90% CrI, 13.0-23.7) percentage points in the proportion of concussions due to hits to the lateral aspect of the head from 80 of 231 concussions (34.6%) to 61 of 457 concussions (13.3%). The incidence of concussions following hits to the head from body checks using the shoulder, arm, and glove was similar before and following the implementation of Rule 48. However, the proportion was reduced 14.7 percentage points from 113 of 231 concussions (48.9%) before to 149 of 457 concussions (32.6%) after implementation of Rule 48 (90% CrI of the difference, 8.9-20.7 percentage points). Conclusions and Relevance: The findings of this cohort study of NHL players suggest that after the introduction of Rule 48, the incidence rate and proportion of concussions from contact to the lateral aspect of the head decreased, as did the proportion of concussions following direct hits to the head.

Youth intentions to provide social support to a peer with a concussion.

OBJECTIVES: 1) To describe demographic factors, concussion knowledge, attitudes, subjective norms, self-efficacy and intentions to provide social support to a peer with a concussion and 2) to examine if demographic factors and concussion knowledge are associated with components of the Theory of Planned Behavior. METHODS: The survey was completed between October 2018 and February 2019 by 200 youth (M = 15.30 years, SD = 1.52). Questions were designed for athletes and non-athletes and inquired about various types of social support. Data analysis included descriptive statistics, Wilcoxon Rank Sum Tests and Spearman's Rank-Order Correlation Coefficients. RESULTS: More favorable attitudes and intentions to provide social support were observed among females (W = 2576, p ≤ 0.001; W = 2411, p ≤ 0.001), older youth (rho = 0.32, p ≤ 0.001; rho = 0.41, p ≤ 0.001) and those with higher concussion knowledge (rho = 0.29, p ≤ 0.001; rho = 0.22; p ≤ 0.001). Participating in sports with a high-risk of concussion was associated with lower attitudes and intentions to provide social support (W = 6677; p ≤ 0.001; W = 6721; p ≤ 0.001). Self-reported concussion history or knowing someone with a concussion history was not significantly associated with social support intentions. CONCLUSION: This study identified characteristics of youth who had positive intentions to provide social support. These findings identify individuals who may model providing social support to a peer, as well as opportunities for future concussion education.

A Continuous Aerobic Resistance Exercise Protocol for Concussion Rehabilitation Delivered Remotely via a Mobile App: Feasibility Study.

BACKGROUND: In recent years, several studies have consistently reported the beneficial effects of aerobic exercise in alleviating symptoms following concussion. However, exercise modality recommendations by practitioners are often limited to traditional exercise equipment (eg, treadmills and stationary bikes). Advances in digital technologies may help to overcome this limitation, as mobile apps can now provide users with high-quality instructional videos, programs, and monitoring capabilities using alternative modalities such as resistance exercises. Mobile technologies are also rapidly expanding to deliver and complement in-person clinical care. Thus, it is imperative to evaluate this emerging technology on its feasibility, safety, and clinical utility for concussion care. OBJECTIVE: The objective of the study was to determine the feasibility of a mobile app to deliver a resistance exercise protocol with minimal equipment to individuals following concussion. Feasibility was defined by retention, adverse events, and achievement of a target heart rate (HR) of 60%±5% (age-adjusted percentage of max: 220 - age). HR data were collected using an Apple Watch, Series 6. Symptoms were evaluated before and after 3 exercise sessions. METHODS: A 2-week, prospective, single-arm pilot study was conducted on 21 adults diagnosed with a concussion. Users were provided a continuous aerobic resistance exercise (CARE) protocol through a mobile app. RESULTS: A total of 18 participants (14 female and 4 male) completed a 3-session exercise plan. The median age-adjusted percent of HR max for session 1 was 55.5% (IQR 49%-63%), 58.1% (IQR 50.8%-65.2%) for session 2, and 57.4% (IQR 49.5%-64.7%) for session 3. Individual median HR% across all sessions ranged from 46.9% to 67.4%; furthermore, 10 participants (55.5%) had a total mean HR% within the target HR%, 7 participants had a mean HR% below 55%, and 1 participant had a mean HR% above 65%. In addition, adherence to the plan resulted in a decrease in reported symptom burden with 94% posterior probability. CONCLUSIONS: Following concussion, a CARE protocol delivered through a mobile app resulted in no adverse effects with 14% (n=3/21) attrition over 3 sessions. CARE was successful in achieving an aerobic exercise intensity of 55%-65% of age-adjusted maximum HR in the majority of participants and resulted in a decrease in reported symptom burden. The potential for this platform in concussion rehabilitation warrants further investigation. Future studies are needed to assess the use of this technology throughout concussion recovery in both individuals with acute concussion, and those with persistent symptoms.

Investigating TSPO levels in occupation-related posttraumatic stress disorder.

Microglia are immune brain cells implicated in stress-related mental illnesses including posttraumatic stress disorder (PTSD). Their role in the pathophysiology of PTSD, and on neurobiological systems that regulate stress, is not completely understood. We tested the hypothesis that microglia activation, in fronto-limbic brain regions involved in PTSD, would be elevated in participants with occupation-related PTSD. We also explored the relationship between cortisol and microglia activation. Twenty participants with PTSD and 23 healthy controls (HC) completed positron emission tomography (PET) scanning of the 18-kDa translocator protein (TSPO), a putative biomarker of microglia activation using the probe [18F]FEPPA, and blood samples for measurement of cortisol. [18F]FEPPA VT was non-significantly elevated (6.5-30%) in fronto-limbic regions in PTSD participants. [18F]FEPPA VT was significantly higher in PTSD participants reporting frequent cannabis use compared to PTSD non-users (44%, p = 0.047). Male participants with PTSD (21%, p = 0.094) and a history of early childhood trauma (33%, p = 0.116) had non-significantly higher [18F]FEPPA VT. Average fronto-limbic [18F]FEPPA VT was positively related to cortisol (r = 0.530, p = 0.028) in the PTSD group only. Although we did not find a significant abnormality in TSPO binding in PTSD, findings suggest microglial activation might have occurred in a subgroup who reported frequent cannabis use. The relationship between cortisol and TSPO binding suggests a potential link between hypothalamic-pituitary-adrenal-axis dysregulation and central immune response to trauma which warrants further study.

Incidence of Remote Near-Point of Convergence in University Athletes After Sport-Related Concussion.

OBJECTIVE: Near-point of convergence (NPC) testing is an attractive screening tool in the sport setting because it is rapid, requires few resources, and is easy to administer. Remote NPC has been reported after sport-related concussion (SRC), although the incidence among a university-aged population is not well defined. The purpose of the study was to examine the incidence of remote NPC after SRC in a cohort of Canadian interuniversity athletes. DESIGN: Cross-sequential. SETTING: University. PARTICIPANTS: One hundred thirty-two university athletes [SRC, n = 68; musculoskeletal (MSK) injury, n = 64] were tested before the beginning of their competitive season and again after their injury. INDEPENDENT VARIABLES: Healthy athletes measured preseason were compared with athletes after SRC or MSK injury using both longitudinal and cross-sectional designs. MAIN OUTCOME MEASURES: Remote NPC (pass/fail), measured at 6 cm or greater, repeated 3 times. RESULTS: After SRC, 22% of athletes failed their test postinjury (95% CI, 14%-33%). Comparatively, in the MSK group, 3% of athletes failed their test postinjury (95% CI, 1%-7%). A direct comparison of both injury groups yielded a mean 19% higher prevalence of failed NPC tests after SRC versus MSK injury (95% CI, 10%-30%). There seems to be no relationship between reported symptom burden and NPC performance after SRC. CONCLUSION: Remote NPC occurs in approximately 1 of 5 athletes after SRC and is rarely observed after MSK injury.

Randomized controlled trial of early aerobic exercise following sport-related concussion: Progressive percentage of age-predicted maximal heart rate versus usual care.

OBJECTIVE: To examine the effect of a readily accessible, structured aerobic exercise intervention on days to asymptomatic status and days to medical clearance compared to usual care exercise prescription in a cohort of adolescents and young adults following sport-related concussion (SRC). METHODS: A longitudinal, randomized, non-blinded clinical trial consisting of a structured aerobic exercise protocol (SAEP) group and a usual care exercise prescription (UCEP) group. Participants in the SAEP group underwent an exercise protocol including 8 sessions over 11 days progressing in duration and intensity stepwise based on participants' age-predicted maximal heart rate. Symptom follow-ups were on days 7, 14, 21, and 28. The primary outcome measures of the study were days to asymptomatic status and days to medical clearance, while the secondary outcome measure was symptom severity on days 7, 14, 21, and 28. RESULTS: 38 participants (SAEP, n = 20; UCEP, n = 19) were recruited and completed all follow-up appointments. Compared to the UCEP group, the SAEP had a faster time to asymptomatic status with 96% posterior probability. In addition, the SAEP group displayed an earlier time to medical clearance with 93% posterior probability. While symptom severity scores did not differ between groups at enrolment (SAEP symptom severity, 30; UCEP, 29), they were subsequently lower in the SAEP group at all assessments throughout the trial with 100% posterior probability. CONCLUSIONS: An aerobic exercise protocol based on percentages of age-predicted maximum heart rate is a safe and effective treatment for reducing symptoms and can be initiated during the first week following SRC. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT02969824.

Characterizing Symptoms Before and Following Concussion in Professional Hockey.

OBJECTIVE: Examine SCAT5 baseline and acute symptom subscales in professional hockey players. DESIGN: Longitudinal case-control. SETTING: Preseason medical evaluations and suspected concussion evaluations. PARTICIPANTS: NHL/AHL players were given the NHL-modified SCAT5 before the 2018-2019 season (n = 1924). During the season, English-speaking players evaluated within 1 day of injury and diagnosed with concussion (n = 140) were compared with players evaluated for possible concussion, but not given a concussion diagnosis (n = 174). INDEPENDENT VARIABLES: Concussion diagnosis and demographic characteristics. MAIN OUTCOME MEASURES: Postconcussion Symptoms Scale (PCSS) items were subdivided into affective/emotional, cognitive, somatic/physical, sleep, and headache subscales. RESULTS: Cognitive (13%), somatic/physical (10%), sleep (26%), affective (18%), and headache (6%) symptoms were reported by players at baseline. Concussed players reported more acute symptoms than active controls on each of the subscales (all P's < 0.001). Players who underwent a suspected concussion evaluation were more likely to be diagnosed with concussion if they reported affective/emotional symptoms at baseline (P < 0.001). Postinjury cognitive (P < 0.001), somatic/physical (P < 0.001), and headache (P < 0.001) symptoms best differentiated concussed players and active controls. CONCLUSIONS: Player reports of increased cognitive difficulties, somatic/physical difficulties, and headache were most associated with concussion diagnosis at the acute evaluation. An abbreviated "acute" PCSS that includes only headache, cognitive, and/or physical symptoms may be useful for diagnostic purposes when evaluation time is limited. Approximately 2% of players reported significantly elevated affective/emotional symptoms at baseline and report of affective/emotional symptoms at baseline was associated with an increased likelihood of concussion diagnosis among players referred for a suspected concussion evaluation.

Tele-Active Rehabilitation for adolescents with concussion: a feasibility study.

Objectives: Active rehabilitation involving subsymptom threshold exercise and education/support promotes recovery among adolescents with concussion, but is typically delivered in-person, which limits accessibility. This study explored the feasibility of a remotely delivered Tele-Active Rehabilitation (Tele-AR) intervention for adolescents with concussion. Methods: A precase-postcase series design was used. Three adolescents (ages 14-17 years) experiencing postconcussion symptoms ≥2 weeks postinjury participated with a parent. The Tele-AR intervention was a 6-week programme supervised by a rehabilitation clinician through weekly videoconferencing appointments and included (1) aerobic exercise, (2) coordination drills and (3) comprehensive education and support. Feasibility indicators included rates of recruitment, retention, adherence, as well as adolescent and parent ratings of technology usability using an adapted Telehealth Usability Questionnaire and satisfaction using the Client Satisfaction Questionnaire-8. Prechanges to postchanges in postconcussion symptoms, illness perceptions, and occupational performance and satisfaction were also assessed. Results: Rates of recruitment (n=3/4) and retention (n=3/3) achieved success criteria. Adherence was high among all participants (77%-100%), and there were no adverse events. Participant ratings of technology usability and satisfaction approached 90%. All participants reported improvements in postconcussion symptoms and illness perception. Clinically significant positive changes were also observed in occupational performance and satisfaction. Conclusions: The Tele-AR intervention appears feasible in a small group of adolescents with concussion, and positive changes were observed in postconcussion symptoms, illness perception and occupational performance. Further study is warranted to evaluate the efficacy of this approach, which may enable access to care that supports recovery in adolescents with concussion.

Determining Sport Concussion Assessment Tool fifth Edition (SCAT5) reliable change in male professional hockey players.

OBJECTIVES: The purpose of this paper is to provide reliable change metrics and assess the test-retest psychometrics of the Sport Concussion Assessment Tool fifth Edition (SCAT5) in a multilingual sample of professional ice hockey players. METHODS: The SCAT5 was administered to National Hockey League and American Hockey League male professional ice hockey players as part of the 2018 and 2019 season medical evaluations. We extracted data from an existing clinical database of players who were administered two consecutive baseline evaluations and had no intervening concussions to assess psychometric properties (eg, test-retest reliability) and develop reliable change metrics. RESULTS: Overall, 1007 players met inclusion criteria. Players were reassessed on average 344.52 (±62.52) days following their first baseline. Test-retest reliability ranged from r=0.3 to r=0.5. Reliable change metrics for Immediate Memory varied considerably dependent on form order. Significant differences were found between English versus non-English language preference on Immediate Memory and Concentration but not Delayed Memory or the modified Balance Error Scoring System (mBESS). Reliable change indices at the 90% CI were: Symptom Severity (5), Total Symptoms (3), Immediate Memory (3-8), Concentration (2), mBESS (5) and Delayed Memory (2-4). CONCLUSIONS: Our findings highlight the importance of considering form differences and language preference when determining reliable change from baseline on the SCAT5 in male professional hockey players. The relatively modest test-retest reliability of the measures leaves room for improved psychometric properties and increased sensitivity to concussion in future iterations of the SCAT.

The Utility of the King-Devick Test in Evaluating Professional Ice Hockey Players With Suspected Concussion.

OBJECTIVE: The purpose of this study was to (1) examine the diagnostic utility of the King-Devick (KD) in professional ice hockey players and (2) determine whether the KD provides unique variance in predicting a diagnosis of concussion when given in combination with the SCAT-5. STUDY DESIGN: Cohort Study. SETTING: Primary care. PATIENTS/PARTICIPANTS: Professional ice hockey players. INDEPENDENT VARIABLES: Diagnosis versus no diagnosis of concussion. MAIN OUTCOME MEASURES: King-Devick and SCAT-5 component scores. METHODS: In part 1, players suspected of having a concussion were evaluated at baseline and acutely with the KD and either the SCAT-3 or the SCAT-5. Players evaluated and not diagnosed with concussion served as active controls. In part 2, a separate group of players suspected of having a concussion was evaluated acutely with both the KD and SCAT-5. RESULTS: In part 1 of this study, 53 concussed players declined in performance on the KD from baseline to acute evaluation, whereas the performance of 76 active controls improved significantly. In part 2 of the study, 75 players were diagnosed with concussion and compared with 80 active controls who were evaluated and not diagnosed with concussion. Concussed players revealed a decline in KD performance from baseline to acute evaluation when compared with controls. However, the KD did not account for significant unique variance in predicting a diagnosis of concussion after accounting for SCAT-5 data. CONCLUSIONS: The KD is useful in differentiating concussed and not concussed athletes acutely, but the KD does not seem to add additional diagnostic value over and above the SCAT-5.

Ten-Word List Performance in Healthy Athletes and Athletes at 3-to-5 Days Following Concussion.

OBJECTIVE: Although the word recall component of the Sport Concussion Assessment Tool (SCAT) was updated from 5-to-10 words, its clinical utility across athletic populations remains unknown. The purpose of this study was to provide normative data on the SCAT-5 10-word test and examine its discriminative ability between healthy university level athletes and those with sport-related concussion (SRC). DESIGN: Cross-sectional. SETTING: University. PARTICIPANTS: Three hundred sixty-three (363, M = 220, F = 153) healthy athletes and 49 (M = 30, F = 19) athletes following SRC. INDEPENDENT VARIABLE: Healthy athletes measured preseason were compared with athletes following an SRC (median = 4.0 days postinjury). MAIN OUTCOME MEASURE: Ten-word list performance from the SCAT-5. RESULTS: There were no significant differences in either immediate ( P = 0.228, Cohen's D = 0.18) or delayed ( P = 0.908, Cohen's D = 0.02) recall tests between athletes with SRC and healthy athletes; the null findings extended to both the male and female subset comparisons. Among healthy athletes, females outperformed males on both immediate (mean difference = 1.0, P < 0.001) and delayed (mean difference = 0.5, P = 0.006) recall tasks. CONCLUSION: Concussion does not seem to impact immediate or delayed recall of the 10-word list in the subacute period following injury. Practitioners should be mindful of sex differences and the time point of administration following injury.

Imaging of astrocytes in posttraumatic stress disorder: A PET study with the monoamine oxidase B radioligand [11C]SL25.1188.

Posttraumatic stress disorder (PTSD) is a debilitating mental health condition that results from exposure to traumatic event(s). Decreased astrocyte-related proteins (e.g., glial fibrillary acidic protein, GFAP) and atrophic astrocytes in corticolimbic brain areas implicated in PTSD have been reported in experimental models suggesting that astrocyte pathology may be a feature of this disorder. We used positron emission tomography (PET) of the monoamine oxidase (MAO)-B probe [11C]SL25.1188 to test the hypothesis that levels of MAO-B, an index of astrocyte levels is decreased in PTSD. MAO-B availability ([11C]SL25.1188 distribution volume) was measured in 13 participants with PTSD (∼39 years, 6F) and 17 healthy controls (HC) (∼31 years, 9F). A magnetic resonance image was acquired to delineate 6 cortiolimbic brain regions. PTSD was associated with a trending reduction in [11C]SL25.1188 availability across regions (8-17%; p = 0.067) implicating the ventral striatum (p uncorrected = 0.015) and medial prefrontal cortex (p uncorrected = 0.060). [11C]SL25.1188 availability was ∼30% lower in corticolimbic regions in PTSD with co-morbid major depressive disorder (MDD) (n = 4) vs HC (p = 0.001) and vs PTSD without MDD (p = 0.005). Our preliminary results do not suggest astrogliosis (inferred from elevated availability) in PTSD, but rather point to a loss of astrocytes or an independent downregulation of MAO-B in PTSD with more severe negative affect. These exploratory findings, which are partly in line with preclinical literature and recent PET observations of decreased microglia marker, Translocator Protein, in PTSD, warrant replication in a larger PTSD cohort.

A Cross-Sectional Decision-Making Approach to Inform Neuropsychological Battery Development in Professional Hockey.

OBJECTIVE: Neuropsychologists commonly use a large battery of tests to inform clinical decisions. Decision analysis can be used to determine which individual tests play a role in the decision-making process. The objective of this project was to conduct quantitative and qualitative decision analysis of decisions by team neuropsychologists with professional hockey players being evaluated as part of the National Hockey League (NHL)/NHL Players Association Concussion Protocol. METHOD: We extracted neuropsychological data from an NHL clinical program database. Team neuropsychologists evaluated concussed players using a hybrid neuropsychological test battery. The neuropsychologists then determined whether players were experiencing concussion-related cognitive difficulties. Logistic regression was used to examine which tests accounted for unique variance in the decision-making process. We also conducted a survey of NHL neuropsychologists, asking them to rate the usefulness of each test in the battery. RESULTS: Five of the fifteen measures accounted for unique variance in team neuropsychologists' decisions, including the ImPACT Verbal Memory Composite, Visual Motor Composite, Reaction Time Composite, Symptom Score, and Brief Visuospatial Memory Test-Revised Delayed Recall. Notable discrepancies were uncovered between quantitative indications of usefulness and self-reported qualitative perceptions of test usefulness when making decisions. Qualitatively, clinicians reported that the Hopkins Verbal Learning Test-Revised, Symbol Digit Modalities Test, ImPACT Reaction Time, and Color Trails 2 were the most useful tests when making decisions. CONCLUSIONS: Along with validation studies, decision analysis can be used as part of a comprehensive evaluation process to inform the development of best-practice batteries for use among athletes with sports concussion.

Cerebral blood flow is associated with matrix metalloproteinase levels during the early symptomatic phase of concussion.

Concussion is associated with disrupted cerebral blood flow (CBF), although there appears to be substantial inter-individual variability in CBF response. At present, the mechanisms of variable CBF response remain incompletely understood, but one potential contributor is matrix metalloproteinase (MMP) expression. In more severe forms of acquired brain injury, MMP up-regulation contributes to CBF impairments via increased blood-brain barrier permeability. A similar relationship is hypothesized for concussion, where recently concussed individuals with higher MMP levels have lower CBF. To test this hypothesis, 35 concussed athletes were assessed longitudinally at early symptomatic injury (median: 5 days post-injury) and at medical clearance (median: 24 days post-injury), along with 71 athletic controls. For all athletes, plasma MMPs were measured and arterial spin labelling was used to measure CBF. Consistent with our hypothesis, higher concentrations of MMP-2 and MMP-3 were correlated with lower global CBF. The correlations between MMPs and global CBF were also significantly diminished for concussed athletes at medical clearance and for athletic controls. These results indicate an inverse relationship between plasma MMP levels and CBF that is specific to the symptomatic phase of concussion. Analyses of regional CBF further showed that correlations with MMP levels exhibited some spatial specificity, with greatest effects in occipital, parietal and temporal lobes. These findings provide new insights into the mechanisms of post-concussion cerebrovascular dysfunction.

Sex differences in acute and long-term brain recovery after concussion.

Concussion is associated with acute disturbances in brain function and behavior, with potential long-term effects on brain health. However, it is presently unclear whether there are sex differences in acute and long-term brain recovery. In this study, magnetic resonance imaging (MRI) was used to scan 61 participants with sport-related concussion (30 male, 31 female) longitudinally at acute injury, medical clearance to return to play (RTP), and 1-year post-RTP. A large cohort of 167 controls (80 male, 87 female) was also imaged. Each MRI session assessed cerebral blood flow (CBF), along with white matter fractional anisotropy (FA) and mean diffusivity (MD). For concussed athletes, the parameters were converted to difference scores relative to matched control subgroups, and partial least squares modeled the main and sex-specific effects of concussion. Although male and female athletes did not differ in acute symptoms or time to RTP , all MRI measures showed significant sex differences during recovery. Males had greater reductions in occipital-parietal CBF (mean difference and 95%CI: 9.97 ml/100 g/min, [4.84, 15.12] ml/100 g/min, z = 3.73) and increases in callosal MD (9.07 × 10-5 , [-14.14, -3.60] × 10-5 , z = -3.46), with greatest effects at 1-year post-RTP. In contrast, females had greater reductions in FA of the corona radiata (16.50 × 10-3 , [-22.38, -11.08] × 10-3 , z = -5.60), with greatest effects at RTP. These findings provide new insights into how the brain recovers after a concussion, showing sex differences in both the acute and chronic phases of injury.

Acute and Chronic Effects of Multiple Concussions on Midline Brain Structures.

OBJECTIVE: To test the hypothesis that a history of concussion (HOC) causes greater disturbances in cerebral blood flow (CBF) and white matter microstructure of midline brain structures after subsequent concussions, during the acute and chronic phases of recovery. METHODS: In this longitudinal magnetic resonance imaging (MRI) study, 61 athletes with uncomplicated concussion (36 with HOC) were imaged at the acute phase of injury (1 to 7 days post-injury), the subacute phase (8 to 14 days), medical clearance to return to play (RTP), one month post-RTP and one year post-RTP. A normative group of 167 controls (73 with HOC) were also imaged. Each session assessed CBF of the cingulate cortex, along with fractional anisotropy (FA) and mean diffusivity (MD) of the corpus callosum. Linear mixed models tested for interactions of HOC with time post-injury. The sport concussion assessment tool (SCAT) was also used to evaluate effects of HOC on symptoms, cognition and balance. RESULTS: Athletes with HOC had greater declines in midcingulate CBF subacutely (z=-3.29, p=0.002) and greater declines in posterior cingulate CBF at one year post-RTP (z=-2.42, p=0.007). No significant effects of HOC were seen for FA, whereas athletes with HOC had higher MD of the splenium at RTP (z=2.54, p=0.008). These effects were seen in the absence of differences in SCAT domains (|z|<1.14, p>0.256) or time to RTP (z=0.23, p=0.818). CONCLUSIONS: Results indicate subacute and chronic effects of HOC on cingulate CBF and callosal microstructure, in the absence of differences in clinical indices. These findings provide new insights into physiological brain recovery after concussion, with cumulative effects of repeated injury detected among young, healthy athletes.

Concussion Risk and Resilience: Relationships with Pre-Injury Salience Network Connectivity.

Concussion is a major health concern, making it critical to identify factors that influence risk and resilience. The salience network (SN) likely plays a key role in concussion risk, given its roles in orienting attention, functional adaptability, and interoceptive awareness. The SN's functions are thought to be mediated through causal control of other networks, including the default mode network (DMN) and executive control network (ECN). It was therefore hypothesized that the SN of at-risk individuals would have altered functional and structural connectivity with the DMN and ECN. For this prospective study, 167 university athletes had baseline clinical assessments and magnetic resonance imaging scans and were monitored for the rest of their varsity career, with any concussions recorded. Athletes concussed in the same season as imaging (CSS; n = 17) and those concussed in later seasons (CLS; n = 15) were matched to controls that were not concussed after imaging. Functional connectivity and white matter fractional anisotropy (FA) were compared between concussed and control groups. Prior to injury, CSS athletes had significantly elevated total symptom severity scores, elevated SN-DMN functional connectivity and reduced FA of connecting white matter tracts, whereas CLS athletes showed no significant clinical or imaging effects. These findings provide new insights into the neurobiology of concussion risk and resilience, as indices of SN-DMN network connectivity are associated with short-term but not long-term concussion risk.

Insular Connectivity Is Associated With Self-Appraisal of Cognitive Function After a Concussion.

Concussion is associated with acute cognitive impairments, with declines in processing speed and reaction time being common. In the clinical setting, these issues are identified via symptom assessments and neurocognitive test (NCT) batteries. Practice guidelines recommend integrating both symptoms and NCTs into clinical decision-making, but correlations between these measures are often poor. This suggests that many patients experience difficulties in the self-appraisal of cognitive issues. It is presently unclear what neural mechanisms give rise to appraisal mismatch after a concussion. One promising target is the insula, which regulates aspects of cognition, particularly interoception and self-monitoring. The present study tested the hypothesis that appraisal mismatch is due to altered functional connectivity of the insula to frontal and midline structures, with hypo-connectivity leading to under-reporting of cognitive issues and hyper-connectivity leading to over-reporting. Data were collected from 59 acutely concussed individuals and 136 normative controls, including symptom assessments, NCTs and magnetic resonance imaging (MRI) data. Analysis of resting-state functional MRI supported the hypothesis, identifying insular networks that were associated with appraisal mismatch in concussed athletes that included frontal, sensorimotor, and cingulate connections. Subsequent analysis of diffusion tensor imaging also determined that symptom over-reporting was associated with reduced fractional anisotropy and increased mean diffusivity of posterior white matter. These findings provide new insights into the mechanisms of cognitive appraisal mismatch after a concussion. They are of particular interest given the central role of symptom assessments in the diagnosis and clinical management of concussion.