Meghan E. Robinson

Biomechanical correlates of symptomatic and asymptomatic neurophysiological impairment in high school football

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.

Military-related traumatic brain injury and neurodegeneration

Mild traumatic brain injury (mTBI) includes concussion, subconcussion, and most exposures to explosive blast from improvised explosive devices. mTBI is the most common traumatic brain injury affecting military personnel; however, it is the most difficult to diagnose and the least well understood. It is also recognized that some mTBIs have persistent, and sometimes progressive, long‐term debilitating effects. Increasing evidence suggests that a single traumatic brain injury can produce long‐term gray and white matter atrophy, precipitate or accelerate age‐related neurodegeneration, and increase the risk of developing Alzheimers disease, Parkinsons disease, and motor neuron disease. In addition, repetitive mTBIs can provoke the development of a tauopathy, chronic traumatic encephalopathy. We found early changes of chronic traumatic encephalopathy in four young veterans of the Iraq and Afghanistan conflict who were exposed to explosive blast and in another young veteran who was repetitively concussed. Four of the five veterans with early‐stage chronic traumatic encephalopathy were also diagnosed with posttraumatic stress disorder. Advanced chronic traumatic encephalopathy has been found in veterans who experienced repetitive neurotrauma while in service and in others who were accomplished athletes. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus; septal abnormalities; and abnormal deposits of hyperphosphorylated tau as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy has clinical and pathological features that overlap with postconcussion syndrome and posttraumatic stress disorder, suggesting that the three disorders might share some biological underpinnings.

Tracking ongoing cognition in individuals using brief, whole-brain functional connectivity patterns

Significance Recently, it was shown that functional connectivity patterns exhibit complex spatiotemporal dynamics at the scale of tens of seconds. Of particular interest is the observation of a limited set of quasi-stable, whole-brain, recurring configurations—commonly referred to as functional connectivity states (FC states)—hypothesized to reflect the continuous flux of cognitive processes. Here, to test this hypothesis, subjects were continuously scanned as they engaged in and transitioned between mental states dictated by tasks. We demonstrate that there is a strong relationship between FC states and ongoing cognition that permits accurate tracking of mental states in individual subjects. We also demonstrate how informative changes in connectivity are not restricted solely to those regions with sustained elevations in activity during task performance. Functional connectivity (FC) patterns in functional MRI exhibit dynamic behavior on the scale of seconds, with rich spatiotemporal structure and limited sets of whole-brain, quasi-stable FC configurations (FC states) recurring across time and subjects. Based on previous evidence linking various aspects of cognition to group-level, minute-to-minute FC changes in localized connections, we hypothesized that whole-brain FC states may reflect the global, orchestrated dynamics of cognitive processing on the scale of seconds. To test this hypothesis, subjects were continuously scanned as they engaged in and transitioned between mental states dictated by tasks. FC states computed within windows as short as 22.5 s permitted robust tracking of cognition in single subjects with near perfect accuracy. Accuracy dropped markedly for subjects with the lowest task performance. Spatially restricting FC information decreased accuracy at short time scales, emphasizing the distributed nature of whole-brain FC dynamics, beyond univariate magnitude changes, as valuable markers of cognition.

Alteration of default mode network in high school football athletes due to repetitive subconcussive mild traumatic brain injury: a resting-state functional magnetic resonance imaging study.

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.

The spatial structure of resting state connectivity stability on the scale of minutes

Resting state functional MRI (rsfMRI) connectivity patterns are not temporally stable, but fluctuate in time at scales shorter than most common rest scan durations (5–10 min). Consequently, connectivity patterns for two different portions of the same scan can differ drastically. To better characterize this temporal variability and understand how it is spatially distributed across the brain, we scanned subjects continuously for 60 min, at a temporal resolution of 1 s, while they rested inside the scanner. We then computed connectivity matrices between functionally-defined regions of interest for non-overlapping 1 min windows, and classified connections according to their strength, polarity, and variability. We found that the most stable connections correspond primarily to inter-hemispheric connections between left/right homologous ROIs. However, only 32% of all within-network connections were classified as most stable. This shows that resting state networks have some long-term stability, but confirms the flexible configuration of these networks, particularly those related to higher order cognitive functions. The most variable connections correspond primarily to inter-hemispheric, across-network connections between non-homologous regions in occipital and frontal cortex. Finally we found a series of connections with negative average correlation, but further analyses revealed that such average negative correlations may be related to the removal of CSF signals during pre-processing. Using the same dataset, we also evaluated how similarity of within-subject whole-brain connectivity matrices changes as a function of window duration (used here as a proxy for scan duration). Our results suggest scanning for a minimum of 10 min to optimize within-subject reproducibility of connectivity patterns across the entire brain, rather than a few predefined networks.

MR spectroscopic evidence of brain injury in the non-diagnosed collision sport athlete.

With growing evidence of long-term neurological damage in individuals enduring repetitive head trauma, it is critical to detect lower-level damage accumulation for the early diagnosis of injury in at-risk populations. Proton magnetic resonance spectroscopic scans of the dorsolateral prefrontal cortex and primary motor cortex were collected from high school American (gridiron) football athletes, prior to and during their competition seasons. Although no concussions were diagnosed, significant metabolic deviations from baseline and non-collision sport controls were revealed. Overall the findings indicate underlying biochemical changes, consequential to repetitive hits, which have previously gone unnoticed due to a lack of traditional neurological symptoms.

Detecting Neurocognitive and Neurophysiological Changes as a Result of Subconcussive Blows Among High School Football Athletes

Recent work suggests that repetitive subconcussive head impacts may contribute to long-term neurodegeneration; however, the risk thresholds for subconcussive injury are unknown. It was hypothesized that the number and severity of head impacts could quantify the risk of developing abnormal neurophysiology. Twenty-one high school boys (ages 14 to 18) participating in varsity and junior varsity football were evaluated over the course of 1 football season (13 games) using a combination of the ImPACT, functional magnetic resonance imaging (fMRI), and head impact telemetry. The number and severity of head impacts throughout the football season were subsequently compared with the fraction of players flagged by either the ImPACT or fMRI before, during, and after the competition season. Twelve of 22 (54.5%) in-season tests of asymptomatic participants had a minimum of 1 composite ImPACT score flagged. For the fMRI analysis, 16 (72.7%) of the 22 in-sea son sessions were considered flagged. Seven assessments were flagged by both the ImPACT and fMRI. Larger numbers of hits appeared to correspond with a larger fraction of players being flagged by at least fMRI or the ImPACT. A substantial number of clinically asymptomatic athletes exhibit significant neurophysi ological changes in-season. Furthermore, the number of head impacts is a risk factor for the development of neurophysiological changes. [Athletic Training & Sports Health Care. 2014;6(x):xxxxxx.] [Query #2: Reduce to 150 words.]

Effects of Repetitive Sub-Concussive Brain Injury on the Functional Connectivity of Default Mode Network in High School Football Athletes

Sub-concussive head impacts are identified as a source of accrued damage. Football athletes experience hundreds of such blows each season. Resting state functional magnetic resonance imaging was used to prospectively study changes in Default Mode Network connectivity for clinically asymptomatic high school football athletes. Athletes exhibited short-term changes relative to baseline and across sessions.

Sub-concussive hit characteristics predict deviant brain metabolism in football athletes

Magnetic resonance spectroscopy and helmet telemetry were used to monitor the neural metabolic response to repetitive head collisions in 25 high school American football athletes. Specific hit characteristics were determined highly predictive of metabolic alterations, suggesting that sub-concussive blows can produce biochemical changes and potentially lead to neurological problems.

Intrinsic functional connectivity predicts individual differences in distractibility

Distractor suppression, the ability to filter and ignore task-irrelevant information, is critical for efficient task performance. While successful distractor suppression relies on a balance of activity in neural networks responsible for attention maintenance (dorsal attention network; DAN), reorientation (ventral attention network; VAN), and internal thought (default mode network, DMN), the degree to which intrinsic connectivity within and between these networks contributes to individual differences in distractor suppression ability is not well-characterized. For the purposes of understanding these interactions, the current study collected resting-state fMRI data from 32 Veterans and, several months later (7±5 months apart), performance on the additional singleton paradigm, a measure of distractor suppression. Using multivariate support vector regression models composed of resting state connectivity between regions of the DAN, VAN, and DMN, and a leave-one-subject-out cross-validation procedure, we were able to predict an individuals task performance, yielding a significant correlation between the actual and predicted distractor suppression (r=0.48, p=0.0053). Network-level analyses revealed that greater within-network DMN connectivity was predictive of better distractor suppression, while greater connectivity between the DMN and attention networks was predictive of poorer distractor suppression. The strongest connection hubs were determined to be the right frontal eye field and temporoparietal junction of the DAN and VAN, respectively, and medial (ventromedial prefrontal and posterior cingulate cortices) and bilateral prefrontal regions of the DMN. These results are amongst a small but growing number of studies demonstrating that resting state connectivity is related to stable individual differences in cognitive ability, and suggest that greater integrity and independence of the DMN is related to better attentional ability.