Multi-site studies are becoming important to increase statistical power, enhance generalizability, and to improve the likelihood of pooling relevant subgroups together—activities which are otherwise ...limited by the availability of subjects or funds at a single site. Even with harmonized imaging sequences, site-dependent variability can mask the advantages of these multi-site studies. The aim of this study was to assess multi-site reproducibility in resting-state functional connectivity “fingerprints”, and to improve identifiability of functional connectomes. The individual fingerprinting of functional connectivity profiles is promising due to its potential as a robust neuroimaging biomarker with which to draw single-subject inferences. We evaluated, on two independent multi-site datasets, individual fingerprints in test-retest visit pairs within and across two sites and present a generalized framework based on principal component analysis to improve identifiability. Those principal components that maximized differential identifiability of a training dataset were used as an orthogonal connectivity basis to reconstruct the individual functional connectomes of training and validation sets. The optimally reconstructed functional connectomes showed a substantial improvement in individual fingerprinting of the subjects within and across the two sites and test-retest visit pairs relative to the original data. A notable increase in ICC values for functional edges and resting-state networks were also observed for reconstructed functional connectomes. Improvements in identifiability were not found to be affected by global signal regression. Post-hoc analyses assessed the effect of the number of fMRI volumes on identifiability and showed that multi-site differential identifiability was for all cases maximized after optimal reconstruction. Finally, the generalizability of the optimal set of orthogonal basis of each dataset was evaluated through a leave-one-out procedure. Overall, results demonstrate that the data-driven framework presented in this study systematically improves identifiability in resting-state functional connectomes in multi-site studies.
Head trauma and concussion in football players have recently received considerable media attention. Postmortem evidence suggests that accrual of damage to the brain may occur with repeated blows to ...the head, even when the individual blows fail to produce clinical symptoms. There is an urgent need for improved detection and characterization of head trauma to reduce future injury risk and promote development of new therapies. In this study we examined neurological performance and health in the presence of head collision events in high school football players, using longitudinal measures of collision events (the HIT(™) System), neurocognitive testing (ImPACT(™)), and functional magnetic resonance imaging MRI (fMRI). Longitudinal assessment (including baseline) was conducted in 11 young men (ages 15-19 years) participating on the varsity and junior varsity football teams at a single high school. We expected and observed subjects in two previously described categories: (1) no clinically-diagnosed concussion and no changes in neurological behavior, and (2) clinically-diagnosed concussion with changes in neurological behavior. Additionally, we observed players in a previously undiscovered third category, who exhibited no clinically-observed symptoms associated with concussion, but who demonstrated measurable neurocognitive (primarily visual working memory) and neurophysiological (altered activation in the dorsolateral prefrontal cortex DLPFC) impairments. This new category was associated with significantly higher numbers of head collision events to the top-front of the head, directly above the DLPFC. The discovery of this new category suggests that more players are suffering neurological injury than are currently being detected using traditional concussion-assessment tools. These individuals are unlikely to undergo clinical evaluation, and thus may continue to participate in football-related activities, even when changes in brain physiology (and potential brain damage) are present, which will increase the risk of future neurological injury.
Abstract Concussion is a growing public health issue in the United States, and chronic traumatic encephalopathy (CTE) is the chief long-term concern linked to repeated concussions. Recently, ...attention has shifted toward subconcussive blows and the role they may play in the development of CTE. We recruited a cohort of high school football players for two seasons of observation. Acceleration sensors were placed in the helmets, and all contact activity was monitored. Pre-season computer-based neuropsychological tests and functional magnetic resonance imaging (fMRI) tests were also obtained in order to assess cognitive and neurophysiological health. In-season follow-up scans were then obtained both from individuals who had sustained a clinically-diagnosed concussion and those who had not. These changes were then related through stepwise regression to history of blows recorded throughout the football season up to the date of the scan. In addition to those subjects who had sustained a concussion, a substantial portion of our cohort who did not sustain concussions showed significant neurophysiological changes. Stepwise regression indicated significant relationships between the number of blows sustained by a subject and the ensuing neurophysiological change. Our findings reinforce the hypothesis that the effects of repetitive blows to the head are cumulative and that repeated exposure to subconcussive blows is connected to pathologically altered neurophysiology.
It has been documented that up to 22% of all soccer injuries are concussions. This is in part due to players purposely using their head to direct the ball during play. To provide a more complete ...understanding of head trauma in soccer athletes, this study characterized the effects of four soccer ball characteristics (size, inflation pressure, mass, velocity) on the resulting peak impact force as it relates to the potential for incurring neurophysiological changes. A total of six hundred trials were performed on size 4 and 5 soccer balls as well as a novel lightweight soccer ball. Impact force was measured with a force plate and ball velocity was determined using motion capture. These data were used, in conjunction with dimensional analysis to relate impact force to ball size, mass, velocity, and pressure. Reasonable reductions in allowable ball parameters resulted in a 19.7% decrease in peak impact force. Adjustments to ball parameters could reduce a high cumulative peak translational acceleration soccer athlete down into a previously defined safer low loading range. In addition, it was noted that water absorption by soccer balls can result in masses that substantially increase impact force and quickly surpass the NCAA weight limit for game play. Additional research is required to determine whether varying soccer ball characteristics will enable soccer players to avoid persistent neurophysiological deficits or what additional interventions may be necessary and the legal implications of these data are discussed.
Participants in American football experience repetitive head impacts that induce negative changes in neurocognitive function over the course of a single season. This study aimed to quantify the ...transfer function connecting the force input to the measured output acceleration of the helmet system to provide a comparison of the impact attenuation of various modern American football helmets. Impact mitigation varied considerably between helmet models and with location for each helmet model. The current data indicate that helmet mass is a key variable driving force attenuation, however flexible helmet shells, helmet shell cutouts, and more compliant padding can improve energy absorption.
The cumulative effect of repetitive subconcussive collisions on the structural and functional integrity of the brain remains largely unknown. Athletes in collision sports, like football, experience a ...large number of impacts across a single season of play. The majority of these impacts, however, are generally overlooked, and their long-term consequences remain poorly understood. This study sought to examine the effects of repetitive collisions across a single competitive season in NCAA Football Bowl Subdivision athletes using advanced neuroimaging approaches. Players were evaluated before and after the season using multiple MRI sequences, including T
-weighted imaging, diffusion tensor imaging (DTI), arterial spin labeling (ASL), resting-state functional MRI (rs-fMRI), and susceptibility weighted imaging (SWI). While no significant differences were found between pre- and post-season for DTI metrics or cortical volumes, seed-based analysis of rs-fMRI revealed significant (
< 0.05) changes in functional connections to right isthmus of the cingulate cortex (ICC), left ICC, and left hippocampus. ASL data revealed significant (
< 0.05) increases in global cerebral blood flow (CBF), with a specific regional increase in right postcentral gyrus. SWI data revealed that 44% of the players exhibited outlier rates (
< 0.05) of regional decreases in SWI signal. Of key interest, athletes in whom changes in rs-fMRI, CBF and SWI were observed were more likely to have experienced high G impacts on a daily basis. These findings are indicative of potential pathophysiological changes in brain integrity arising from only a single season of participation in the NCAA Football Bowl Subdivision, even in the absence of clinical symptoms or a diagnosis of concussion. Whether these changes reflect compensatory adaptation to cumulative head impacts or more lasting alteration of brain integrity remains to be further explored.
The theory and techniques of compressed sensing (CS) have shown their potential as a breakthrough in accelerating k-space data acquisition for parallel magnetic resonance imaging (pMRI). However, the ...performance of CS reconstruction models in pMRI has not been fully maximized, and CS recovery guarantees for pMRI are largely absent. To improve reconstruction accuracy from parsimonious amounts of k-space data while maintaining flexibility, a new CS SENSitivity Encoding (SENSE) pMRI reconstruction framework promoting joint sparsity (JS) across channels (JS CS SENSE) is proposed in this paper. The recovery guarantee derived for the proposed JS CS SENSE model is demonstrated to be better than that of the conventional CS SENSE model and similar to that of the coil-by-coil CS model. The flexibility of the new model is better than the coil-by-coil CS model and the same as that of CS SENSE. For fast image reconstruction and fair comparisons, all the introduced CS-based constrained optimization problems are solved with split Bregman, variable splitting, and combined-variable splitting techniques. For the JS CS SENSE model in particular, these techniques lead to an efficient algorithm. Numerical experiments show that the reconstruction accuracy is significantly improved by JS CS SENSE compared with the conventional CS SENSE. In addition, an accurate residual-JS regularized sensitivity estimation model is also proposed and extended to calibration-less (CaL) JS CS SENSE. Numerical results show that CaL JS CS SENSE outperforms other state-of-the-art CS-based calibration-less methods in particular for reconstructing non-piecewise constant images.
American football has become the focus of numerous studies highlighting a growing concern that cumulative exposure to repetitive, sports-related head acceleration events (HAEs) may have negative ...consequences for brain health, even in the absence of a diagnosed concussion. In this longitudinal study, brain functional connectivity was analyzed in a cohort of high school American football athletes over a single play season and compared against participants in non-collision high school sports. Football athletes underwent four resting-state functional magnetic resonance imaging sessions: once before (pre-season), twice during (in-season), and once 34-80 days after the contact activities play season ended (post-season). For each imaging session, functional connectomes (FCs) were computed for each athlete and compared across sessions using a metric reflecting the (self) similarity between two FCs. HAEs were monitored during all practices and games throughout the season using head-mounted sensors. Relative to the pre-season scan session, football athletes exhibited decreased FC self-similarity at the later in-season session, with apparent recovery of self-similarity by the time of the post-season session. In addition, both within and post-season self-similarity was correlated with cumulative exposure to head acceleration events. These results suggest that repetitive exposure to HAEs produces alterations in functional brain connectivity and highlight the necessity of collision-free recovery periods for football athletes.
It is commonly believed that cerebrospinal fluid (CSF) movement is facilitated by blood vessel wall movements (i.e., hemodynamic oscillations) in the brain. A coherent pattern of low frequency ...hemodynamic oscillations and CSF movement was recently found during non-rapid eye movement (NREM) sleep via functional MRI. This finding raises other fundamental questions: 1) the explanation of coupling between hemodynamic oscillations and CSF movement from fMRI signals; 2) the existence of the coupling during wakefulness; 3) the direction of CSF movement. In this resting state fMRI study, we proposed a mechanical model to explain the coupling between hemodynamics and CSF movement through the lens of fMRI. Time delays between CSF movement and global hemodynamics were calculated. The observed delays between hemodynamics and CSF movement match those predicted by the model. Moreover, by conducting separate fMRI scans of the brain and neck, we confirmed the low frequency CSF movement at the fourth ventricle is bidirectional. Our finding also demonstrates that CSF movement is facilitated by changes in cerebral blood volume mainly in the low frequency range, even when the individual is awake.
Long-term neurological damage as a result of head trauma while playing sports is a major concern for football athletes today. Repetitive concussions have been linked to many neurological disorders. ...Recently, it has been reported that repetitive subconcussive events can be a significant source of accrued damage. Since football athletes can experience hundreds of subconcussive hits during a single season, it is of utmost importance to understand their effect on brain health in the short and long term. In this study, resting-state functional magnetic resonance imaging (rs-fMRI) was used to study changes in the default mode network (DMN) after repetitive subconcussive mild traumatic brain injury. Twenty-two high school American football athletes, clinically asymptomatic, were scanned using the rs-fMRI for a single season. Baseline scans were acquired before the start of the season, and follow-up scans were obtained during and after the season to track the potential changes in the DMN as a result of experienced trauma. Ten noncollision-sport athletes were scanned over two sessions as controls. Overall, football athletes had significantly different functional connectivity measures than controls for most of the year. The presence of this deviation of football athletes from their healthy peers even before the start of the season suggests a neurological change that has accumulated over the years of playing the sport. Football athletes also demonstrate short-term changes relative to their own baseline at the start of the season. Football athletes exhibited hyperconnectivity in the DMN compared to controls for most of the sessions, which indicates that, despite the absence of symptoms typically associated with concussion, the repetitive trauma accrued produced long-term brain changes compared to their healthy peers.
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