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The objective of this study was to examine associations of lifetime concussion history (CHx) and an advanced metric of lifetime repetitive head impact exposure with resting-state functional connectivity (rsFC) across the whole-brain and among large-scale functional networks (Default Mode; Dorsal Attention; and Frontoparietal Control) in former collegiate football players. Individuals who completed at least one year of varsity collegiate football were eligible to participate in this observational cohort study ( n = 48; aged 36–41 years; 79.2% white/Caucasian; 12.5±4.4 years of football played; all men). Individuals were excluded if they reported history/suspicion of psychotic disorder with active symptoms, contraindications to participation in study procedures (e.g., MRI safety concern), or inability to travel. Each participant provided concussion and football playing histories. Self-reported concussion history was analyzed in two different ways based on prior research: dichotomous “High” (≥3 concussions; n = 28) versus “Low” (<3 concussions; n = 20); and four ordinal categories (0–1 concussion [ n = 19]; 2–4 concussions [ n = 8]; 5–7 concussions [ n = 9]; and ≥8 concussions [ n = 12]). The Head Impact Exposure Estimate (HIEE) was calculated from football playing history captured via structured interview. Resting-state fMRI and T1-weighted MRI were acquired and preprocessed using established pipelines. Next, rsFC was calculated using the Seitzman et al., (2020) 300-ROI functional atlas. Whole-brain, within-network, and between-network rsFC were calculated using all ROIs and network-specific ROIs, respectively. Effects of CHx and HIEE on rsFC values were examined using separate multivariable linear regression models, with a-priori α set to 0.05. We observed no statistically significant associations between rsFC outcomes and either CHx or HIEE ( p s ≥ .12). Neither CHx nor HIEE were associated with neural signatures that have been observed in studies of typical and pathological aging. While CHx and repetitive head impacts have been associated with changes in brain health in older former athletes, our preliminary results suggest that associations with rsFC may not be present in early midlife former football players.

Purpose of ReviewSport-related concussion (SRC) and mild traumatic brain injury (mTBI) have been thrust into the national spotlight, with youth athletes bearing the burden of this public health problem. The current review aims to provide a practical summary of pediatric SRC, including key terminology, return to play/school, and risk factors for post-concussion syndrome (PCS).Recent FindingsWhile the majority of youth athletes recover within 2 to 4 weeks, approximately 10% of athletes experience a protracted recovery with symptoms lasting months, impacting social, scholastic, and sporting activities.SummaryIn the pediatric population, the strongest predictors of PCS are initial symptom burden and prior concussion, with mixed results behind the factors of gender, headaches, and learning disability. The role of psychiatric, family history, sports, and socioeconomic factors remain in their infancy.

This study examined the relationship between patient performance on multiple memory measures and regional brain volumes using an FDA-cleared quantitative volumetric analysis program - Neuroreader™. Ninety-two patients diagnosed with mild cognitive impairment (MCI) by a clinical neuropsychologist completed cognitive evaluations and underwent MR Neuroreader™ within 1 year of testing. Select brain regions were correlated with three widely used memory tests. Regression analyses were conducted to determine if using more than one memory measures would better predict hippocampal z-scores and to explore the added value of recognition memory to prediction models. Memory performances were most strongly correlated with hippocampal volumes than other brain regions. After controlling for encoding/Immediate Recall standard scores, statistically significant correlations emerged between Delayed Recall and hippocampal volumes (rs ranging from .348 to .490). Regression analysis revealed that evaluating memory performance across multiple memory measures is a better predictor of hippocampal volume than individual memory performances. Recognition memory did not add further predictive utility to regression analyses. This study provides support for use of MR Neuroreader™ hippocampal volumes as a clinically informative biomarker associated with memory performance, which is a critical diagnostic feature of MCI phenotype.

ObjectivesTo systematically review the scientific literature regarding the acute assessment of sport-related concussion (SRC) and provide recommendations for improving the Sport Concussion Assessment Tool (SCAT6).Data sourcesSystematic searches of seven databases from 2001 to 2022 using key words and controlled vocabulary relevant to concussion, sports, SCAT, and acute evaluation.Eligibility criteria(1) Original research articles, cohort studies, case–control studies, and case series with a sample of >10; (2) ≥80% SRC; and (3) studies using a screening tool/technology to assess SRC acutely (<7 days), and/or studies containing psychometric/normative data for common tools used to assess SRC.Data extractionSeparate reviews were conducted involving six subdomains: Cognition, Balance/Postural Stability, Oculomotor/Cervical/Vestibular, Emerging Technologies, and Neurological Examination/Autonomic Dysfunction. Paediatric/Child studies were included in each subdomain. Risk of Bias and study quality were rated by coauthors using a modified SIGN (Scottish Intercollegiate Guidelines Network) tool.ResultsOut of 12 192 articles screened, 612 were included (189 normative data and 423 SRC assessment studies). Of these, 183 focused on cognition, 126 balance/postural stability, 76 oculomotor/cervical/vestibular, 142 emerging technologies, 13 neurological examination/autonomic dysfunction, and 23 paediatric/child SCAT. The SCAT discriminates between concussed and non-concussed athletes within 72 hours of injury with diminishing utility up to 7 days post injury. Ceiling effects were apparent on the 5-word list learning and concentration subtests. More challenging tests, including the 10-word list, were recommended. Test–retest data revealed limitations in temporal stability. Studies primarily originated in North America with scant data on children.ConclusionSupport exists for using the SCAT within the acute phase of injury. Maximal utility occurs within the first 72 hours and then diminishes up to 7 days after injury. The SCAT has limited utility as a return to play tool beyond 7 days. Empirical data are limited in pre-adolescents, women, sport type, geographical and culturally diverse populations and para athletes.PROSPERO registration numberCRD42020154787.

ObjectiveDetermine the role of fluid-based biomarkers, advanced neuroimaging, genetic testing and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion (SRC).DesignSystematic review.Data sourcesSearches of seven databases from 1 January 2001 through 24 March 2022 using keywords and index terms relevant to concussion, sports and neurobiological recovery. Separate reviews were conducted for studies involving neuroimaging, fluid biomarkers, genetic testing and emerging technologies. A standardised method and data extraction tool was used to document the study design, population, methodology and results. Reviewers also rated the risk of bias and quality of each study.Eligibility criteria for selecting studiesStudies were included if they: (1) were published in English; (2) represented original research; (3) involved human research; (4) pertained only to SRC; (5) included data involving neuroimaging (including electrophysiological testing), fluid biomarkers or genetic testing or other advanced technologies used to assess neurobiological recovery after SRC; (6) had a minimum of one data collection point within 6 months post-SRC; and (7) contained a minimum sample size of 10 participants.ResultsA total of 205 studies met inclusion criteria, including 81 neuroimaging, 50 fluid biomarkers, 5 genetic testing, 73 advanced technologies studies (4 studies overlapped two separate domains). Numerous studies have demonstrated the ability of neuroimaging and fluid-based biomarkers to detect the acute effects of concussion and to track neurobiological recovery after injury. Recent studies have also reported on the diagnostic and prognostic performance of emerging technologies in the assessment of SRC. In sum, the available evidence reinforces the theory that physiological recovery may persist beyond clinical recovery after SRC. The potential role of genetic testing remains unclear based on limited research.ConclusionsAdvanced neuroimaging, fluid-based biomarkers, genetic testing and emerging technologies are valuable research tools for the study of SRC, but there is not sufficient evidence to recommend their use in clinical practice.PROSPERO registration numberCRD42020164558.

[...]some have maintained that we must not only consider those cases that are considered ‘false positives’ (i.e., those who believe they have CTE, but in reality do not), but also the possible ‘false negatives’ (i.e., those who do not believe they have CTE, but may in fact do) (14). [...]efforts have been made to pass legislation that bans youth tackle football (16). Based on this notion, our commentary aims to: 1)summarize the concerns related to reduced team sport participation and declining physical activity in our youth; 2)describe the benefits of team sports; and 3)offer recommendations regarding team sport participation that address both concerns over long-term adverse neurologic outcomes and our collective role to ensure safe sport settings. Given that children’s confidence and self-esteem have been associated with their decision to participate in physical activity/sport (49), limiting sport options may result in decreased participation (34). [...]it is important that as we argue for the benefits of team sport participation, we acknowledge the potential limitations in its availability and advocate for the equitable creation of a variety of team sport opportunities for boys and girls.

ObjectiveThis study investigated the longitudinal course of depressive symptom severity over 19 years in former American football players and the influence of concussion history, contact sport participation and physical function on observed trajectories.MethodsFormer American football players completed a general health questionnaire involving demographic information, medical/psychiatric history, concussion/football history and validated measures of depression and physical function at three time points (2001, 2010 and 2019). Parallel process latent growth curve modelling tested associations between concussion history, years of football participation, and overall and change in physical function on the overall level and trajectory of depressive symptoms.ResultsAmong the 333 participants (mean(SD) age, 48.95 (9.37) at enrolment), there was a statistically significant, but small increase in depressive symptom severity from 2001 (48.34 (7.75)) to 2019 (49.77 (9.52)), slope=0.079 (SE=0.11), p=0.007. Those with greater concussion history endorsed greater overall depressive symptom severity, B=1.38 (SE=0.33), p<0.001. Concussion history, B<0.001 (SE=0.02), p=0.997 and years of participation, B<0.001 (SE=0.01), p=0.980, were not associated with rate of change (slope factor) over 19 years. Greater decline in physical function, B=−0.71 (SE=0.16), p<0.001, was predictive of a faster growth rate (ie, steeper increase) of depression symptom endorsement over time.ConclusionsConcussion history, not years of participation, was associated with greater depressive symptom severity. Neither factor was predictive of changes over a 19-year period. Decline in physical function was a significant predictor of a steeper trajectory of increased depressive symptoms, independent of concussion effects. This represents one viable target for preventative intervention to mitigate long-term neuropsychiatric difficulties associated with concussion across subsequent decades of life.

Changes in cortical gray matter are a key feature of neurodegenerative diseases that have been linked with concussion and repetitive head impacts (RHIs). Prior evidence implicates prior concussion and RHI in reduced cortical thickness or volume in temporal and frontal regions, with results largely restricted to older retired contact sport athletes. Fewer studies have investigated similar associations in younger athletes or applied approaches to capture more subtle differences in gray matter earlier in the lifespan. The current study assessed the association of concussion and RHI with cortical macrostructure (cortical thickness, cortical surface area), and cortical microstructure (cortical mean diffusivity), the latter of which has been suggested to be an earlier marker of gray matter abnormalities in neurodegenerative diseases. A total of 207 otherwise healthy collegiate‐aged athletes completed semistructured interviews for concussion and sport participation history, as well as a magnetic resonance imaging session including anatomical and diffusion imaging (N = 205 with available diffusion data). Cortical surface area and cortical thickness were estimated using FreeSurfer; cortical mean diffusivity was calculated with correction for partial volume. Bayesian multilevel modeling was conducted on regions of interest derived from Desikan–Killiany Atlas parcellations to determine the association of the number of prior concussions and RHI (included in the same models) with each metric, controlling for sex, age, and intracranial volume (area only). There was strong evidence for a positive association between the number of prior concussions and cortical mean diffusivity throughout most of the cortex. In addition, there was strong evidence for a positive association of the number of prior concussions with cortical surface area across several regions. For cortical thickness, there was strong evidence of inverse associations between the number of prior concussions and anterior and medial temporal cortical regions only. In contrast, only weak to no evidence of associations between years of contact sport exposure, a proxy for RHI, and any cortical surface metric was observed. These results demonstrate that cortical diffusivity may represent a more sensitive metric of subtle, early structural changes associated with repetitive neurotrauma, and highlight the importance of efforts to reduce concussion risk in sport. A greater number of prior concussions was associated with widespread increases in cortical mean diffusivity, increased cortical surface area, and thinner anterior and medial temporal cortex in otherwise healthy collegiate athletes. Microscopic changes in gray matter associated with cumulative concussion may represent a vulnerability or antecedent to future degeneration.

Years of sport participation (YoP) is conventionally used to estimate cumulative repetitive head impacts (RHI) experienced by contact sport athletes. The relationship of this measure to other estimates of head impact exposure and the potential associations of these measures with neurobehavioral functioning are unknown. We investigated the association between YoP and the Head Impact Exposure Estimate (HIEE), and whether associations between the two estimates of exposure and neurobehavioral functioning varied. Former American football players (N = 58; age = 37.9 ± 1.5 years) completed in-person evaluations approximately 15 years following sport discontinuation. Assessments consisted of neuropsychological assessment and structured interviews of head impact history (i.e., HIEE). General linear models were fit to test the association between YoP and the HIEE, and their associations with neurobehavioral outcomes. YoP was weakly correlated with the HIEE, p = .005, R2 = .13. Higher YoP was associated with worse performance on the Symbol Digit Modalities Test, p = .004, R2 = .14, and Trail Making Test-B, p = .001, R2 = .18. The HIEE was associated with worse performance on the Delayed Recall trial of the Hopkins Verbal Learning Test-Revised, p = .020, R2 = .09, self-reported cognitive difficulties (Neuro-QoL Cognitive Function), p = .011, R2 = .10, psychological distress (Brief Symptom Inventory-18), p = .018, R2 = .10, and behavioral regulation (Behavior Rating Inventory of Executive Function for Adults), p = .017, R2 = .10. YoP was marginally associated with the HIEE, a comprehensive estimate of head impacts sustained over a career. Associations between each exposure estimate and neurobehavioral functioning outcomes differed. Findings have meaningful implications for efforts to accurately quantify the risk of adverse long-term neurobehavioral outcomes potentially associated with RHI.