Characterizing major depressive disorder and substance use disorder using heatmaps and variable interactions: The utility of operant behavior and brain structure relationships.

BACKGROUND: Rates of depression and addiction have risen drastically over the past decade, but the lack of integrative techniques remains a barrier to accurate diagnoses of these mental illnesses. Changes in reward/aversion behavior and corresponding brain structures have been identified in those with major depressive disorder (MDD) and cocaine-dependence polysubstance abuse disorder (CD). Assessment of statistical interactions between computational behavior and brain structure may quantitatively segregate MDD and CD. METHODS: Here, 111 participants [40 controls (CTRL), 25 MDD, 46 CD] underwent structural brain MRI and completed an operant keypress task to produce computational judgment metrics. Three analyses were performed: (1) linear regression to evaluate groupwise (CTRL v. MDD v. CD) differences in structure-behavior associations, (2) qualitative and quantitative heatmap assessment of structure-behavior association patterns, and (3) the k-nearest neighbor machine learning approach using brain structure and keypress variable inputs to discriminate groups. RESULTS: This study yielded three primary findings. First, CTRL, MDD, and CD participants had distinct structure-behavior linear relationships, with only 7.8% of associations overlapping between any two groups. Second, the three groups had statistically distinct slopes and qualitatively distinct association patterns. Third, a machine learning approach could discriminate between CTRL and CD, but not MDD participants. CONCLUSIONS: These findings demonstrate that variable interactions between computational behavior and brain structure, and the patterns of these interactions, segregate MDD and CD. This work raises the hypothesis that analysis of interactions between operant tasks and structural neuroimaging might aide in the objective classification of MDD, CD and other mental health conditions.

Predicting COVID-19 Vaccination Uptake Using a Small and Interpretable Set of Judgment and Demographic Variables: Cross-Sectional Cognitive Science Study.

BACKGROUND: Despite COVID-19 vaccine mandates, many chose to forgo vaccination, raising questions about the psychology underlying how judgment affects these choices. Research shows that reward and aversion judgments are important for vaccination choice; however, no studies have integrated such cognitive science with machine learning to predict COVID-19 vaccine uptake. OBJECTIVE: This study aims to determine the predictive power of a small but interpretable set of judgment variables using 3 machine learning algorithms to predict COVID-19 vaccine uptake and interpret what profile of judgment variables was important for prediction. METHODS: We surveyed 3476 adults across the United States in December 2021. Participants answered demographic, COVID-19 vaccine uptake (ie, whether participants were fully vaccinated), and COVID-19 precaution questions. Participants also completed a picture-rating task using images from the International Affective Picture System. Images were rated on a Likert-type scale to calibrate the degree of liking and disliking. Ratings were computationally modeled using relative preference theory to produce a set of graphs for each participant (minimum R2>0.8). In total, 15 judgment features were extracted from these graphs, 2 being analogous to risk and loss aversion from behavioral economics. These judgment variables, along with demographics, were compared between those who were fully vaccinated and those who were not. In total, 3 machine learning approaches (random forest, balanced random forest [BRF], and logistic regression) were used to test how well judgment, demographic, and COVID-19 precaution variables predicted vaccine uptake. Mediation and moderation were implemented to assess statistical mechanisms underlying successful prediction. RESULTS: Age, income, marital status, employment status, ethnicity, educational level, and sex differed by vaccine uptake (Wilcoxon rank sum and chi-square P<.001). Most judgment variables also differed by vaccine uptake (Wilcoxon rank sum P<.05). A similar area under the receiver operating characteristic curve (AUROC) was achieved by the 3 machine learning frameworks, although random forest and logistic regression produced specificities between 30% and 38% (vs 74.2% for BRF), indicating a lower performance in predicting unvaccinated participants. BRF achieved high precision (87.8%) and AUROC (79%) with moderate to high accuracy (70.8%) and balanced recall (69.6%) and specificity (74.2%). It should be noted that, for BRF, the negative predictive value was <50% despite good specificity. For BRF and random forest, 63% to 75% of the feature importance came from the 15 judgment variables. Furthermore, age, income, and educational level mediated relationships between judgment variables and vaccine uptake. CONCLUSIONS: The findings demonstrate the underlying importance of judgment variables for vaccine choice and uptake, suggesting that vaccine education and messaging might target varying judgment profiles to improve uptake. These methods could also be used to aid vaccine rollouts and health care preparedness by providing location-specific details (eg, identifying areas that may experience low vaccination and high hospitalization).

Longitudinal changes in resting state fMRI brain self-similarity of asymptomatic high school American football athletes.

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.

The Relationship Between a History of High-risk and Destructive Behaviors and COVID-19 Infection: Preliminary Study.

BACKGROUND: The COVID-19 pandemic has heightened mental health concerns, but the temporal relationship between mental health conditions and SARS-CoV-2 infection has not yet been investigated. Specifically, psychological issues, violent behaviors, and substance use were reported more during the COVID-19 pandemic than before the pandemic. However, it is unknown whether a prepandemic history of these conditions increases an individual's susceptibility to SARS-CoV-2. OBJECTIVE: This study aimed to better understand the psychological risks underlying COVID-19, as it is important to investigate how destructive and risky behaviors may increase a person's susceptibility to COVID-19. METHODS: In this study, we analyzed data from a survey of 366 adults across the United States (aged 18 to 70 years); this survey was administered between February and March of 2021. The participants were asked to complete the Global Appraisal of Individual Needs-Short Screener (GAIN-SS) questionnaire, which indicates an individual's history of high-risk and destructive behaviors and likelihood of meeting diagnostic criteria. The GAIN-SS includes 7 questions related to externalizing behaviors, 8 related to substance use, and 5 related to crime and violence; responses were given on a temporal scale. The participants were also asked whether they ever tested positive for COVID-19 and whether they ever received a clinical diagnosis of COVID-19. GAIN-SS responses were compared between those who reported and those who did not report COVID-19 to determine if those who reported COVID-19 also reported GAIN-SS behaviors (Wilcoxon rank sum test, α=.05). In total, 3 hypotheses surrounding the temporal relationships between the recency of GAIN-SS behaviors and COVID-19 infection were tested using proportion tests (α=.05). GAIN-SS behaviors that significantly differed (proportion tests, α=.05) between COVID-19 responses were included as independent variables in multivariable logistic regression models with iterative downsampling. This was performed to assess how well a history of GAIN-SS behaviors statistically discriminated between those who reported and those who did not report COVID-19. RESULTS: Those who reported COVID-19 more frequently indicated past GAIN-SS behaviors (Q<0.05). Furthermore, the proportion of those who reported COVID-19 was higher (Q<0.05) among those who reported a history of GAIN-SS behaviors; specifically, gambling and selling drugs were common across the 3 proportion tests. Multivariable logistic regression revealed that GAIN-SS behaviors, particularly gambling, selling drugs, and attention problems, accurately modeled self-reported COVID-19, with model accuracies ranging from 77.42% to 99.55%. That is, those who exhibited destructive and high-risk behaviors before and during the pandemic could be discriminated from those who did not exhibit these behaviors when modeling self-reported COVID-19. CONCLUSIONS: This preliminary study provides insights into how a history of destructive and risky behaviors influences infection susceptibility, offering possible explanations for why some persons may be more susceptible to COVID-19, potentially in relation to reduced adherence to prevention guidelines or not seeking vaccination.

Anxiety, Post-COVID-19 Syndrome-Related Depression, and Suicidal Thoughts and Behaviors in COVID-19 Survivors: Cross-sectional Study.

BACKGROUND: Although the mental health impacts of COVID-19 on the general population have been well studied, studies of the long-term impacts of COVID-19 on infected individuals are relatively new. To date, depression, anxiety, and neurological symptoms associated with post-COVID-19 syndrome (PCS) have been observed in the months following COVID-19 recovery. Suicidal thoughts and behavior (STB) have also been preliminarily proposed as sequelae of COVID-19. OBJECTIVE: We asked 3 questions. First, do participants reporting a history of COVID-19 diagnosis or a close relative having severe COVID-19 symptoms score higher on depression (Patient Health Questionnaire-9 [PHQ-9]) or state anxiety (State Trait Anxiety Index) screens than those who do not? Second, do participants reporting a COVID-19 diagnosis score higher on PCS-related PHQ-9 items? Third, do participants reporting a COVID-19 diagnosis or a close relative having severe COVID-19 symptoms score higher in STB before, during, or after the first year of the pandemic? METHODS: This preliminary study analyzed responses to a COVID-19 and mental health questionnaire obtained from a US population sample, whose data were collected between February 2021 and March 2021. We used the Mann-Whitney U test to detect differences in the medians of the total PHQ-9 scores, PHQ-9 component scores, and several STB scores between participants claiming a past clinician diagnosis of COVID-19 and those denying one, as well as between participants claiming severe COVID-19 symptoms in a close relative and those denying them. Where significant differences existed, we created linear regression models to predict the scores based on COVID-19 response as well as demographics to identify potential confounding factors in the Mann-Whitney relationships. Moreover, for STB scores, which corresponded to 5 questions asking about 3 different time intervals (i.e., past 1 year or more, past 1 month to 1 year, and past 1 month), we developed repeated-measures ANOVAs to determine whether scores tended to vary over time. RESULTS: We found greater total depression (PHQ-9) and state anxiety (State Trait Anxiety Index) scores in those with COVID-19 history than those without (Bonferroni P=.001 and Bonferroni P=.004) despite a similar history of diagnosed depression and anxiety. Greater scores were noted for a subset of depression symptoms (PHQ-9 items) that overlapped with the symptoms of PCS (all Bonferroni Ps<.05). Moreover, we found greater overall STB scores in those with COVID-19 history, equally in time windows preceding, during, and proceeding infection (all Bonferroni Ps<.05). CONCLUSIONS: We confirm previous studies linking depression and anxiety diagnoses to COVID-19 recovery. Moreover, our findings suggest that depression diagnoses associated with COVID-19 history relate to PCS symptoms, and that STB associated with COVID-19 in some cases precede infection.

The Prevalence of Psychotic Symptoms, Violent Ideation, and Disruptive Behavior in a Population With SARS-CoV-2 Infection: Preliminary Study.

BACKGROUND: The COVID-19 disease results from infection by the SARS-CoV-2 virus to produce a range of mild to severe physical, neurological, and mental health symptoms. The COVID-19 pandemic has indirectly caused significant emotional distress, triggering the emergence of mental health symptoms in individuals who were not previously affected or exacerbating symptoms in those with existing mental health conditions. Emotional distress and certain mental health conditions can lead to violent ideation and disruptive behavior, including aggression, threatening acts, deliberate harm toward other people or animals, and inattention to or noncompliance with education or workplace rules. Of the many mental health conditions that can be associated with violent ideation and disruptive behavior, psychosis can evidence greater vulnerability to unpredictable changes and being at a greater risk for them. Individuals with psychosis can also be more susceptible to contracting COVID-19 disease. OBJECTIVE: This study aimed to investigate whether violent ideation, disruptive behavior, or psychotic symptoms were more prevalent in a population with COVID-19 and did not precede the pandemic. METHODS: In this preliminary study, we analyzed questionnaire responses from a population sample (N=366), received between the end of February 2021 and the start of March 2021 (1 year into the COVID-19 pandemic), regarding COVID-19 illness, violent ideation, disruptive behavior, and psychotic symptoms. Using the Wilcoxon rank sum test followed by multiple comparisons correction, we compared the self-reported frequency of these variables for 3 time windows related to the past 1 month, past 1 month to 1 year, and >1 year ago among the distributions of people who answered whether they tested positive or were diagnosed with COVID-19 by a clinician. We also used multivariable logistic regression with iterative resampling to investigate the relationship between these variables occurring >1 year ago (ie, before the pandemic) and the likelihood of contracting COVID-19. RESULTS: We observed a significantly higher frequency of self-reported violent ideation, disruptive behavior, and psychotic symptoms, for all 3 time windows of people who tested positive or were diagnosed with COVID-19 by a clinician. Using multivariable logistic regression, we observed 72% to 94% model accuracy for an increased incidence of COVID-19 in participants who reported violent ideation, disruptive behavior, or psychotic symptoms >1 year ago. CONCLUSIONS: This preliminary study found that people who reported a test or clinician diagnosis of COVID-19 also reported higher frequencies of violent ideation, disruptive behavior, or psychotic symptoms across multiple time windows, indicating that they were not likely to be the result of COVID-19. In parallel, participants who reported these behaviors >1 year ago (ie, before the pandemic) were more likely to be diagnosed with COVID-19, suggesting that violent ideation, disruptive behavior, in addition to psychotic symptoms, were associated with COVID-19 with an approximately 70% to 90% likelihood.

American Football Position-Specific Neurometabolic Changes in High School Athletes: A Magnetic Resonance Spectroscopic Study.

Reports estimate between 1.6-3.8 million sports-related concussions occur annually, with 30% occurring in youth male American football athletes. Many studies report neurophysiological changes in these athletes, but the exact reasons for these changes remain elusive. Investigation of injury mechanics highlights a need to address how player position might impact these changes. Here, 55 high school American football athletes (20 linemen; 35 non-linemen) underwent magnetic resonance spectroscopy four times over the course of a football season-once prior to the season (Pre), twice during (In1, In2), and once following (Post) to quantify metabolites (N-acetyl aspartate, choline, creatine, myo-inositol, and glutamate/glutamine) in the dorsolateral prefrontal cortex (DLPFC) and primary motor cortex (M1). Head acceleration events (HAEs) were monitored at each practice and game. Spectroscopic and HAE data were analyzed by imaging session and player position. Linear regression analyses were conducted between metabolite levels and HAEs, and metabolite levels in football athletes were compared with age-and gender-matched non-contact athletes. Across-season (i.e., between Pre and In1, In2, Post), different DLPFC and M1 metabolites decreased (p < 0.05) according to player position (i.e., linemen vs. non-linemen). The majority of regression results involved DLPFC metabolites in linemen, where metabolite levels were higher from Pre to Post, with increasing HAE load. Comparisons with control athletes revealed higher metabolite levels in football athletes both before and after the season. This study highlights the importance of player position when conducting analyses on American football athletes and demonstrates elevated DLPFC and M1 brain metabolites in football athletes compared with control athletes at both Pre and Post, suggesting potential HAE-related neurocompensatory mechanisms.

A preliminary model of football-related neural stress that integrates metabolomics with transcriptomics and virtual reality.

Research suggests contact sports affect neurological health. This study used permutation-based mediation statistics to integrate measures of metabolomics, neuroinflammatory miRNAs, and virtual reality (VR)-based motor control to investigate multi-scale relationships across a season of collegiate American football. Fourteen significant mediations (six pre-season, eight across-season) were observed where metabolites always mediated the statistical relationship between miRNAs and VR-based motor control ( p S o b e l p e r m ≤ 0.05; total effect > 50%), suggesting a hypothesis that metabolites sit in the statistical pathway between transcriptome and behavior. Three results further supported a model of chronic neuroinflammation, consistent with mitochondrial dysfunction: (1) Mediating metabolites were consistently medium-to-long chain fatty acids, (2) tricarboxylic acid cycle metabolites decreased across-season, and (3) accumulated head acceleration events statistically moderated pre-season metabolite levels to directionally model post-season metabolite levels. These preliminary findings implicate potential mitochondrial dysfunction and highlight probable peripheral blood biomarkers underlying repetitive head impacts in otherwise healthy collegiate football athletes.

Metabolomic response to collegiate football participation: Pre- and Post-season analysis.

Contact sports participation has been shown to have both beneficial and detrimental effects on health, however little is known about the metabolic sequelae of these effects. We aimed to identify metabolite alterations across a collegiate American football season. Serum was collected from 23 male collegiate football athletes before the athletic season (Pre) and after the last game (Post). Samples underwent nontargeted metabolomic profiling and 1131 metabolites were included for univariate, pathway enrichment, and multivariate analyses. Significant metabolites were assessed against head acceleration events (HAEs). 200 metabolites changed from Pre to Post (P < 0.05 and Q < 0.05); 160 had known identity and mapped to one of 57 pre-defined biological pathways. There was significant enrichment of metabolites belonging to five pathways (P < 0.05): xanthine, fatty acid (acyl choline), medium chain fatty acid, primary bile acid, and glycolysis, gluconeogenesis, and pyruvate metabolism. A set of 12 metabolites was sufficient to discriminate Pre from Post status, and changes in 64 of the 200 metabolites were also associated with HAEs (P < 0.05). In summary, the identified metabolites, and candidate pathways, argue there are metabolic consequences of both physical training and head impacts with football participation. These findings additionally identify a potential set of objective biomarkers of repetitive head injury.

Preliminary Report: Localized Cerebral Blood Flow Mediates the Relationship between Progesterone and Perceived Stress Symptoms among Female Collegiate Club Athletes after Mild Traumatic Brain Injury.

Female athletes are under-studied in the field of concussion research, despite evidence of higher injury prevalence and longer recovery time. Hormonal fluctuations caused by the natural menstrual cycle (MC) or hormonal contraceptive (HC) use impact both post-injury symptoms and neuroimaging findings, but the relationships among hormone, symptoms, and brain-based measures have not been jointly considered in concussion studies. In this preliminary study, we compared cerebral blood flow (CBF) measured with arterial spin labeling between concussed female club athletes 3-10 days after mild traumatic brain injury (mTBI) and demographic, HC/MC matched controls (CON). We tested whether CBF statistically mediates the relationship between progesterone serum levels and post-injury symptoms, which may support a hypothesis for progesterone's role in neuroprotection. We found a significant three-way relationship among progesterone, CBF, and perceived stress score (PSS) in the left middle temporal gyrus for the mTBI group. Higher progesterone was associated with lower (more normative) PSS, as well as higher (more normative) CBF. CBF mediates 100% of the relationship between progesterone and PSS (Sobel p value = 0.017). These findings support a hypothesis for progesterone having a neuroprotective role after concussion and highlight the importance of controlling for the effects of sex hormones in future concussion studies.

Global and peak local specific absorption rate control on parallel transmit systems using k-means SAR compression model.

PURPOSE: To improve the specific absorption rate (SAR) compression model capability in parallel transmission (pTx) MRI systems. METHODS: A k-means clustering method is proposed to group voxels with similar SAR behaviors in the scanned object, providing a controlled upper-bounded estimation of peak local SARs. This k-means compression model and the conventional virtual observation point (VOP) model were tested in a pTx MRI framework. The pTx pulse design with different SAR controlling schemes was simulated using a numerical human head model and an eight-channel 7T coil array. Multiple criteria (including RF power, global and peak local SARs, and excitation accuracy) were compared for the performance testing. RESULTS: The k-means compression model generated a narrower overestimation bound, leading to a more accurate local SAR estimation. Among different pTx pulse design approaches, the k-means compression model showed the best trade-off between the SAR and excitation accuracy. CONCLUSIONS: The developed SAR compression model is advantageous for pTx framework given the narrower overestimation bound and control over the compression ratio. Results also illustrate that a moderate increase of maximum RF power can be useful for reducing the maximum local SAR deposition.

Brain Perfusion Mediates the Relationship Between miRNA Levels and Postural Control.

Transcriptomics, regional cerebral blood flow (rCBF), and a virtual reality-based spatial motor task were integrated using mediation analysis in a novel demonstration of "imaging omics." Data collected in National Collegiate Athletic Association (NCAA) Division I football athletes cleared for play before in-season training showed significant relationships in 1) elevated levels of miR-30d and miR-92a to elevated putamen rCBF, 2) elevated putamen rCBF to compromised Balance scores, and 3) compromised Balance scores to elevated microRNA (miRNA) levels. rCBF acted as a consistent mediator variable (Sobel's test P < 0.05) between abnormal miRNA levels and compromised Balance scores. Given the involvement of these miRNAs in inflammation and immune function and that vascular perfusion is a component of the inflammatory response, these findings support a chronic inflammatory model in these athletes with 11 years of average football exposure. rCBF, a systems biology measure, was necessary for miRNA to affect behavior.

Every hit matters: White matter diffusivity changes in high school football athletes are correlated with repetitive head acceleration event exposure.

Recent evidence of short-term alterations in brain physiology associated with repeated exposure to moderate intensity subconcussive head acceleration events (HAEs), prompts the question whether these alterations represent an underlying neural injury. A retrospective analysis combining counts of experienced HAEs and longitudinal diffusion-weighted imaging explored whether greater exposure to incident mechanical forces was associated with traditional diffusion-based measures of neural injury-reduced fractional anisotropy (FA) and increased mean diffusivity (MD). Brains of high school athletes (N = 61) participating in American football exhibited greater spatial extents (or volumes) experiencing substantial changes (increases and decreases) in both FA and MD than brains of peers who do not participate in collision-based sports (N = 15). Further, the spatial extents of the football athlete brain exhibiting traditional diffusion-based markers of neural injury were found to be significantly correlated with the cumulative exposure to HAEs having peak translational acceleration exceeding 20 g. This finding demonstrates that subconcussive HAEs induce low-level neurotrauma, with prolonged exposure producing greater accumulation of neural damage. The duration and extent of recovery associated with periods in which athletes do not experience subconcussive HAEs now represents a priority for future study, such that appropriate participation and training schedules may be developed to minimize the risk of long-term neurological dysfunction.

Uncovering multi-site identifiability based on resting-state functional connectomes.

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.

Dependence on subconcussive impacts of brain metabolism in collision sport athletes: an MR spectroscopic study.

Long term neurological impairments due to repetitive head trauma are a growing concern for collision sport athletes. American Football has the highest rate of reported concussions among male high school athletes, a position held by soccer for female high school athletes. Recent research has shown that subconcussive events experienced by collision sport athletes can be a further significant source of accrued damage. Collision sport athletes experience hundreds of subconcussive events in a single season, and these largely go uninvestigated as they produce no overt clinical symptoms. Continued participation by these seemingly uninjured athletes is hypothesized to increase susceptibility to diagnoseable brain injury. This study paired magnetic resonance spectroscopy with head impact monitoring to quantify the relationship between metabolic changes and head acceleration event characteristics in high school-aged male football and female soccer collision sport athletes. During the period of exposure to subconcussive events, asymptomatic male (football) collision sport athletes exhibited statistically significant changes in concentrations of glutamate+glutamine (Glx) and total choline containing compounds (tCho) in dorsolateral prefrontal cortex, and female (soccer) collision sport athletes exhibited changes in glutamate+glutamine (Glx) in primary motor cortex. Neurometabolic alterations observed in football athletes during the second half of the season were found to be significantly associated with the average acceleration per head acceleration events, being best predicted by the accumulation of events exceeding 50 g. These marked deviations in neurometabolism, in the absence of overt symptoms, raise concern about the neural health of adolescent collision-sport athletes and suggest limiting exposure to head acceleration events may help to ameliorate the risk of subsequent cognitive impairment.