Identification of Concussion Subtypes Based on Intrinsic Brain Activity.

Importance: The identification of brain activity-based concussion subtypes at time of injury has the potential to advance the understanding of concussion pathophysiology and to optimize treatment planning and outcomes. Objective: To investigate the presence of intrinsic brain activity-based concussion subtypes, defined as distinct resting state quantitative electroencephalography (qEEG) profiles, at the time of injury. Design, Setting, and Participants: In this retrospective, multicenter (9 US universities and high schools and 4 US clinical sites) cohort study, participants aged 13 to 70 years with mild head injuries were included in longitudinal cohort studies from 2017 to 2022. Patients had a clinical diagnosis of concussion and were restrained from activity by site guidelines for more than 5 days, with an initial Glasgow Coma Scale score of 14 to 15. Participants were excluded for known neurological disease or history of traumatic brain injury within the last year. Patients were assessed with 2 minutes of artifact-free EEG acquired from frontal and frontotemporal regions within 120 hours of head injury. Data analysis was performed from July 2021 to June 2023. Main Outcomes and Measures: Quantitative features characterizing the EEG signal were extracted from a 1- to 2-minute artifact-free EEG data for each participant, within 120 hours of injury. Symptom inventories and days to return to activity were also acquired. Results: From the 771 participants (mean [SD] age, 20.16 [5.75] years; 432 male [56.03%]), 600 were randomly selected for cluster analysis according to 471 qEEG features. Participants and features were simultaneously grouped into 5 disjoint subtypes by a bootstrapped coclustering algorithm with an overall agreement of 98.87% over 100 restarts. Subtypes were characterized by distinctive profiles of qEEG measure sets, including power, connectivity, and complexity, and were validated in the independent test set. Subtype membership showed a statistically significant association with time to return to activity. Conclusions and Relevance: In this cohort study, distinct subtypes based on resting state qEEG activity were identified within the concussed population at the time of injury. The existence of such physiological subtypes supports different underlying pathophysiology and could aid in personalized prognosis and optimization of care path.

A multimodal biomarker for concussion identification, prognosis and management.

BACKGROUND: Prompt, accurate, objective assessment of concussion is crucial, particularly for children/adolescents and young adults. While there is currently no gold standard for the diagnosis of concussion, the importance of multidimensional/multimodal assessments has recently been emphasized. METHODS: Concussed subjects (N = 177), matched controls (N = 187) and healthy volunteers (N = 204) represented a convenience sample of male and female subjects between the ages of 13 and 25 years, enrolled at 29 Colleges and 19 High Schools in the US. Subjects were tested at time of injury and at multiple time points during recovery. Assessments included EEG, neurocognitive tests and standard concussion assessment tools. Multimodal classifiers to maximally separate controls from concussed subjects with prolonged recovery (≥14 days) were derived using quantitative EEG, neurocognitive and vestibular measures, informed feature reduction and a Genetic Algorithm methodology for classifier derivation. The methodology protected against overtraining using an internal cross-validation framework. An enhanced multimodal Brain Function Index (eBFI) was derived from the classifier output and mapped to a percentile scale which expressed the index relative to non-injured controls. RESULTS: At time of injury eBFIs were significantly different between controls and concussed subjects with prolonged recovery, showing return to non-concussed levels at return-to-play plus 45 days. For the combined concussed population, and for the short recovery subjects, a more rapid recovery was seen. CONCLUSIONS: This multivariate, multimodal, objective index of brain function impairment can potentially be used, along with other tools, to aid in diagnosis, assessment, and tracking of recovery from concussion.