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.

Long-Term Changes in Brain Connectivity Reflected in Quantitative Electrophysiology of Symptomatic Former National Football League Players.

Exposure to repetitive head impacts (RHI) has been associated with long-term disturbances in cognition, mood, and neurobehavioral dysregulation, and reflected in neuroimaging. Distinct patterns of changes in quantitative features of the brain electrical activity (quantitative electroencephalogram [qEEG]) have been demonstrated to be sensitive to brain changes seen in neurodegenerative disorders and in traumatic brain injuries (TBI). While these qEEG biomarkers are highly sensitive at time of injury, the long-term effects of exposure to RHI on brain electrical activity are relatively unexplored. Ten minutes of eyes closed resting EEG data were collected from a frontal and frontotemporal electrode montage (BrainScope Food and Drug Administration-cleared EEG acquisition device), as well as assessments of neuropsychiatric function and age of first exposure (AFE) to American football. A machine learning methodology was used to derive a qEEG-based algorithm to discriminate former National Football League (NFL) players (n = 87, 55.40 ± 7.98 years old) from same-age men without history of RHI (n = 68, 54.94 ± 7.63 years old), and a second algorithm to discriminate former players with AFE <12 years (n = 33) from AFE ≥12 years (n = 54). The algorithm separating NFL retirees from controls had a specificity = 80%, a sensitivity = 60%, and an area under curve (AUC) = 0.75. Within the NFL population, the algorithm separating AFE <12 from AFE ≥12 resulted in a sensitivity = 76%, a specificity = 52%, and an AUC = 0.72. The presence of a profile of EEG abnormalities in the NFL retirees and in those with younger AFE includes features associated with neurodegeneration and the disruption of neuronal transmission between regions. These results support the long-term consequences of RHI and the potential of EEG as a biomarker of persistent changes in brain function.

Harmonized-Multinational qEEG norms (HarMNqEEG).

This paper extends frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. (i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. (ii) We also show that harmonized Riemannian norms produce z-scores with increased diagnostic accuracy predicting brain dysfunction produced by malnutrition in the first year of life and detecting COVID induced brain dysfunction. (iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings.

Early protein energy malnutrition impacts life-long developmental trajectories of the sources of EEG rhythmic activity.

Protein Energy Malnutrition (PEM) has lifelong consequences on brain development and cognitive function. We studied the lifelong developmental trajectories of resting-state EEG source activity in 66 individuals with histories of Protein Energy Malnutrition (PEM) limited to the first year of life and in 83 matched classmate controls (CON) who are all participants of the 49 years longitudinal Barbados Nutrition Study (BNS). qEEGt source z-spectra measured deviation from normative values of EEG rhythmic activity sources at 5-11 years of age and 40 years later at 45-51 years of age. The PEM group showed qEEGt abnormalities in childhood, including a developmental delay in alpha rhythm maturation and an insufficient decrease in beta activity. These profiles may be correlated with accelerated cognitive decline.

A Proposed Brain-, Spine-, and Mental- Health Screening Methodology (NEUROSCREEN) for Healthcare Systems: Position of the Society for Brain Mapping and Therapeutics.

The COVID-19 pandemic has accelerated neurological, mental health disorders, and neurocognitive issues. However, there is a lack of inexpensive and efficient brain evaluation and screening systems. As a result, a considerable fraction of patients with neurocognitive or psychobehavioral predicaments either do not get timely diagnosed or fail to receive personalized treatment plans. This is especially true in the elderly populations, wherein only 16% of seniors say they receive regular cognitive evaluations. Therefore, there is a great need for development of an optimized clinical brain screening workflow methodology like what is already in existence for prostate and breast exams. Such a methodology should be designed to facilitate objective early detection and cost-effective treatment of such disorders. In this paper we have reviewed the existing clinical protocols, recent technological advances and suggested reliable clinical workflows for brain screening. Such protocols range from questionnaires and smartphone apps to multi-modality brain mapping and advanced imaging where applicable. To that end, the Society for Brain Mapping and Therapeutics (SBMT) proposes the Brain, Spine and Mental Health Screening (NEUROSCREEN) as a multi-faceted approach. Beside other assessment tools, NEUROSCREEN employs smartphone guided cognitive assessments and quantitative electroencephalography (qEEG) as well as potential genetic testing for cognitive decline risk as inexpensive and effective screening tools to facilitate objective diagnosis, monitor disease progression, and guide personalized treatment interventions. Operationalizing NEUROSCREEN is expected to result in reduced healthcare costs and improving quality of life at national and later, global scales.

Quantitative EEG Tomography of Early Childhood Malnutrition.

The goal of this study is to identify the quantitative electroencephalographic (qEEG) signature of early childhood malnutrition [protein-energy malnutrition (PEM)]. To this end, archival digital EEG recordings of 108 participants in the Barbados Nutrition Study (BNS) were recovered and cleaned of artifacts (46 children who suffered an episode of PEM limited to the first year of life) and 62 healthy controls). The participants of the still ongoing BNS were initially enrolled in 1973, and EEGs for both groups were recorded in 1977-1978 (at 5-11 years). Scalp and source EEG Z-spectra (to correct for age effects) were obtained by comparison with the normative Cuban Human Brain Mapping database. Differences between both groups in the z spectra (for all electrode locations and frequency bins) were assessed by t-tests with thresholds corrected for multiple comparisons by permutation tests. Four clusters of differences were found: (a) increased theta activity (3.91-5.86 Hz) in electrodes T4, O2, Pz and in the sources of the supplementary motor area (SMA); b) decreased alpha1 (8.59-8.98 Hz) in Fronto-central electrodes and sources of widespread bilateral prefrontal are; (c) increased alpha2 (11.33-12.50 Hz) in Temporo-parietal electrodes as well as in sources in Central-parietal areas of the right hemisphere; and (d) increased beta (13.67-18.36 Hz), in T4, T5 and P4 electrodes and decreased in the sources of bilateral occipital-temporal areas. Multivariate Item Response Theory of EEGs scored visually by experts revealed a neurophysiological latent variable which indicated excessive paroxysmal and focal abnormality activity in the PEM group. A robust biomarker construction procedure based on elastic-net regressions and 1000-cross-validations was used to: (i) select stable variables and (ii) calculate the area under ROC curves (AUC). Thus, qEEG differentiate between the two nutrition groups (PEM vs Control) performing as well as visual inspection of the EEG scored by experts (AUC = 0.83). Since PEM is a global public health problem with lifelong neurodevelopmental consequences, our finding of consistent differences between PEM and controls, both in qualitative and quantitative EEG analysis, suggest that this technology may be a source of scalable and affordable biomarkers for assessing the long-term brain impact of early PEM.

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.

A Brain Electrical Activity Electroencephalographic-Based Biomarker of Functional Impairment in Traumatic Brain Injury: A Multi-Site Validation Trial.

The potential clinical utility of a novel quantitative electroencephalographic (EEG)-based Brain Function Index (BFI) as a measure of the presence and severity of functional brain injury was studied as part of an independent prospective validation trial. The BFI was derived using quantitative EEG (QEEG) features associated with functional brain impairment reflecting current consensus on the physiology of concussive injury. Seven hundred and twenty adult patients (18-85 years of age) evaluated within 72 h of sustaining a closed head injury were enrolled at 11 U.S. emergency departments (EDs). Glasgow Coma Scale (GCS) score was 15 in 97%. Standard clinical evaluations were conducted and 5 to 10 min of EEG acquired from frontal locations. Clinical utility of the BFI was assessed for raw scores and percentile values. A multinomial logistic regression analysis demonstrated that the odds ratios (computed against controls) of the mild and moderate functionally impaired groups were significantly different from the odds ratio of the computed tomography (CT) postive (CT+, structural injury visible on CT) group (p = 0.0009 and p = 0.0026, respectively). However, no significant differences were observed between the odds ratios of the mild and moderately functionally impaired groups. Analysis of variance (ANOVA) demonstrated significant differences in BFI among normal (16.8%), mild TBI (mTBI)/concussed with mild or moderate functional impairment, (61.3%), and CT+ (21.9%) patients (p < 0.0001). Regression slopes of the odds ratios for likelihood of group membership suggest a relationship between the BFI and severity of impairment. Findings support the BFI as a quantitative marker of brain function impairment, which scaled with severity of functional impairment in mTBI patients. When integrated into the clinical assessment, the BFI has the potential to aid in early diagnosis and thereby potential to impact the sequelae of TBI by providing an objective marker that is available at the point of care, hand-held, non-invasive, and rapid to obtain.

Exploration of the Pathophysiology of Chronic Pain Using Quantitative EEG Source Localization.

Chronic pain affects more than 35% of the US adult population representing a major public health imperative. Currently, there are no objective means for identifying the presence of pain, nor for quantifying pain severity. Through a better understanding of the pathophysiology of pain, objective indicators of pain might be forthcoming. Brain mechanisms mediating the painful state were imaged in this study, using source localization of the EEG. In a population of 77 chronic pain patients, significant overactivation of the "Pain Matrix" or pain network, was found in brain regions including, the anterior cingulate, anterior and posterior insula, parietal lobule, thalamus, S1, and dorsolateral prefrontal cortex (DLPFC), consistent with those reported with conventional functional imaging, and extended to include the mid and posterior cingulate, suggesting that the increased temporal resolution of electrophysiological measures may allow a more precise identification of the pain network. Significant differences between those who self-report high and low pain were reported for some of the regions of interest (ROIs), maximally on left hemisphere in the DLPFC, suggesting encoding of pain intensity occurs in a subset of pain network ROIs. Furthermore, a preliminary multivariate logistic regression analysis was used to select quantitative-EEG features which demonstrated a highly significant predictive relationship of self-reported pain scores. Findings support the potential to derive a quantitative measure of the severity of pain using information extracted from a multivariate descriptor of the abnormal overactivation. Furthermore, the frequency specific (theta/low alpha band) overactivation in the regions reported, while not providing direct evidence, are consistent with a model of thalamocortical dysrhythmia as the potential mechanism of the neuropathic painful condition.

The Use of an Electrophysiological Brain Function Index in the Evaluation of Concussed Athletes.

OBJECTIVE: To evaluate the effectiveness of the electroencephalographic (EEG) Brain Function Index (BFI) for characterizing sports-related concussive injury and recovery. PARTICIPANTS: Three hundred fifty-four (354) male contact sport high school and college athletes were prospectively recruited from multiple locations over 6 academic years of play (244 control baseline athletes and 110 athletes with a concussion). METHODS: Using 5 to 10 minutes of eyes closed resting EEG collected from frontal and frontotemporal regions, a BFI was computed for all subjects and sessions. Group comparisons were performed to test for the significance of the difference in the BFI score between the controls at baseline and athletes with a concussion at several time points. RESULTS: There was no significant difference in BFI between athletes with a concussion at baseline (ie, prior to injury) and controls at baseline (P = .4634). Athletes with a concussion, tested within 72 hours of injury, exhibited significant differences in BFI compared with controls (P = .0036). The significant differences in BFI were no longer observed at 45 days following injury (P = .19). CONCLUSION: Controls and athletes with a concussion exhibited equivalent BFI scores at preseason baseline. The concussive injury (measured within 72 hours) significantly affected brain function reflected in the BFI in the athletes with a concussion. The BFI of the athletes with a concussion returned to levels seen in controls by day 45, suggesting recovery. The BFI may provide an important objective marker of concussive injury and recovery.

Increased prognostic accuracy of TBI when a brain electrical activity biomarker is added to loss of consciousness (LOC).

BACKGROUND: Extremely high accuracy for predicting CT+ traumatic brain injury (TBI) using a quantitative EEG (QEEG) based multivariate classification algorithm was demonstrated in an independent validation trial, in Emergency Department (ED) patients, using an easy to use handheld device. This study compares the predictive power using that algorithm (which includes LOC and amnesia), to the predictive power of LOC alone or LOC plus traumatic amnesia. PARTICIPANTS: ED patients 18-85years presenting within 72h of closed head injury, with GSC 12-15, were study candidates. 680 patients with known absence or presence of LOC were enrolled (145 CT+ and 535 CT- patients). METHODS: 5-10min of eyes closed EEG was acquired using the Ahead 300 handheld device, from frontal and frontotemporal regions. The same classification algorithm methodology was used for both the EEG based and the LOC based algorithms. Predictive power was evaluated using area under the ROC curve (AUC) and odds ratios. RESULTS: The QEEG based classification algorithm demonstrated significant improvement in predictive power compared with LOC alone, both in improved AUC (83% improvement) and odds ratio (increase from 4.65 to 16.22). Adding RGA and/or PTA to LOC was not improved over LOC alone. CONCLUSIONS: Rapid triage of TBI relies on strong initial predictors. Addition of an electrophysiological based marker was shown to outperform report of LOC alone or LOC plus amnesia, in determining risk of an intracranial bleed. In addition, ease of use at point-of-care, non-invasive, and rapid result using such technology suggests significant value added to standard clinical prediction.

Emergency Department Triage of Traumatic Head Injury Using a Brain Electrical Activity Biomarker: A Multisite Prospective Observational Validation Trial.

OBJECTIVES: A brain electrical activity biomarker for identifying traumatic brain injury (TBI) in emergency department (ED) patients presenting with high Glasgow Coma Scale (GCS) after sustaining a head injury has shown promise for objective, rapid triage. The main objective of this study was to prospectively evaluate the efficacy of an automated classification algorithm to determine the likelihood of being computed tomography (CT) positive, in high-functioning TBI patients in the acute state. METHODS: Adult patients admitted to the ED for evaluation within 72 hours of sustaining a closed head injury with GCS 12 to 15 were candidates for study. A total of 720 patients (18-85 years) meeting inclusion/exclusion criteria were enrolled in this observational, prospective validation trial, at 11 U.S. EDs. GCS was 15 in 97%, with the first and third quartiles being 15 (interquartile range = 0) in the study population at the time of the evaluation. Standard clinical evaluations were conducted and 5 to 10 minutes of electroencephalogram (EEG) was acquired from frontal and frontal-temporal scalp locations. Using an a priori derived EEG-based classification algorithm developed on an independent population and applied to this validation population prospectively, the likelihood of each subject being CT+ was determined, and performance metrics were computed relative to adjudicated CT findings. RESULTS: Sensitivity of the binary classifier (likely CT+ or CT-) was 92.3% (95% confidence interval [CI] = 87.8%-95.5%) for detection of any intracranial injury visible on CT (CT+), with specificity of 51.6% (95% CI = 48.1%-55.1%) and negative predictive value (NPV) of 96.0% (95% CI = 93.2%-97.9%). Using ternary classification (likely CT+, equivocal, likely CT-) demonstrated enhanced sensitivity to traumatic hematomas (≥1 mL of blood), 98.6% (95% CI = 92.6%-100.0%), and NPV of 98.2% (95% CI = 95.5%-99.5%). CONCLUSION: Using an EEG-based biomarker high accuracy of predicting the likelihood of being CT+ was obtained, with high NPV and sensitivity to any traumatic bleeding and to hematomas. Specificity was significantly higher than standard CT decision rules. The short time to acquire results and the ease of use in the ED environment suggests that EEG-based classifier algorithms have potential to impact triage and clinical management of head-injured patients.

The quantified EEG characteristics of responders and non-responders to long-term treatment with atomoxetine in children with attention deficit hyperactivity disorders.

OBJECTIVE: The aim of our study is to examine quantitative Electroencephalogram (QEEG) differences between ADHD patients that are responders and non-responders to long-term treatment with Atomoxetine at baseline and after 6 and 12months of treatment. Patients with attention deficit hyperactivity disorder (ADHD) received atomoxetine titrated, over 7days, from 0.5 to 1.2mg/kg/day. QEEG and Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV) scores were recorded before treatment and after therapy. METHODS: Twenty minutes of eyes closed resting EEG was recorded from 19 electrodes referenced to linked earlobes. Full frequency and narrow band spectra of two minutes of artifact-free EEG were computed as well as source localization using Variable Resolution Electrical Tomography (VARETA). Abnormalities were identified using Z-spectra relative to normative values. RESULTS: Patients were classified as responders, non-responders and partial responders based upon the SNAP-IV findings. At baseline, the responders showed increased absolute power in alpha and delta in frontal and temporal regions, whereas, non-responders showed increased absolute power in all frequency bands that was widely distributed. With treatment responders' absolute power values moved toward normal values, whereas, non-responders remained at baseline values. CONCLUSIONS: Patients with increased power in the alpha band with no evidence of alterations in the beta or theta range, might be responders to treatment with atomoxetine. Increased power in the beta band coupled with increased alpha seems to be related to non-responders and one should consider atomoxetine withdrawal, especially if there is persistence of increased alpha and beta accompanied by an increase of theta.

Comparison of quantitative EEG to current clinical decision rules for head CT use in acute mild traumatic brain injury in the ED.

STUDY OBJECTIVE: We compared the performance of a handheld quantitative electroencephalogram (QEEG) acquisition device to New Orleans Criteria (NOC), Canadian CT Head Rule (CCHR), and National Emergency X-Radiography Utilization Study II (NEXUS II) Rule in predicting intracranial lesions on head computed tomography (CT) in acute mild traumatic brain injury in the emergency department (ED). METHODS: Patients between 18 and 80 years of age who presented to the ED with acute blunt head trauma were enrolled in this prospective observational study at 2 urban academic EDs in Detroit, MI. Data were collected for 10 minutes from frontal leads to determine a QEEG discriminant score that could maximally classify intracranial lesions on head CT. RESULTS: One hundred fifty-two patients were enrolled from July 2012 to February 2013. A total 17.1% had acute traumatic intracranial lesions on head CT. Quantitative electroencephalogram discriminant score of greater than or equal to 31 was found to be a good cutoff (area under receiver operating characteristic curve = 0.84; 95% confidence interval [CI], 0.76-0.93) to classify patients with positive head CT. The sensitivity of QEEG discriminant score was 92.3 (95% CI, 73.4-98.6), whereas the specificity was 57.1 (95% CI, 48.0-65.8). The sensitivity and specificity of the decision rules were as follows: NOC 96.1 (95% CI, 78.4-99.7) and 15.8 (95% CI, 10.1-23.6); CCHR 46.1 (95% CI, 27.1-66.2) and 86.5 (95% CI, 78.9-91.7); NEXUS II 96.1 (95% CI, 78.4-99.7) and 31.7 (95% CI, 23.9-40.7). CONCLUSION: At a sensitivity of greater than 90%, QEEG discriminant score had better specificity than NOC and NEXUS II. Only CCHR had better specificity than QEEG discriminant score but at the cost of low (<50%) sensitivity.

Identification of acute stroke using quantified brain electrical activity.

OBJECTIVES: Acute stroke is a leading cause of brain injury and death and requires rapid and accurate diagnosis. Noncontrast head computed tomography (CT) is the first line for diagnosis in the emergency department (ED). Complicating rapid triage are presenting conditions that clinically mimic stroke. There is an extensive literature reporting clinical utility of brain electrical activity in early diagnosis and management of acute stroke. However, existing technologies do not lend themselves to easily acquired rapid evaluation. This investigation used an independently derived classifier algorithm for the identification of traumatic structural brain injury based on brain electrical activity recorded from a reduced frontal montage to explore the potential clinical utility of such an approach in acute stroke assessment. METHODS: Adult patients (age 18 to 95 years) presenting with stroke-like and/or altered mental status symptoms were recruited from urban academic EDs as part of a large research study evaluating the clinical utility of quantitative brain electrical activity in acutely brain-injured patients. All patients from the parent study who had confirmed strokes, and a control group of stroke mimics (those with final ED diagnoses of migraine or syncope), were selected for this study. All stroke patients underwent head CT scans. Some patients with negative CTs had further imaging with magnetic resonance imaging (MRI). Ten minutes of electroencephalographic data were acquired on a hand-held device in development, from five frontal electrodes. Data analyses were done offline. A Structural Brain Injury Index (SBII) was derived using an independently developed binary discriminant classification algorithm whose input was specified features of brain electrical activity. The SBII was previously found to have high accuracy in the identification of traumatic brain-injured patients who were found to have brain injury on CT (CT+). This algorithm was applied to patients in this study and used to classify patients as CT+ or not CT+. Performance was assessed using sensitivity, specificity, and negative and positive predictive values (NPV, PPV). RESULTS: Forty-eight stroke patients (31 ischemic and 17 hemorrhagic) and 135 stroke mimic controls were included. Within the ischemic population, approximately half were CT- but later confirmed for stroke with MRI (CT-/MRI+). Sensitivity to stroke was 91.7%, specificity 50.4% (to stroke mimic), NPV 94.4%, and PPV 39.6%. Eighty percent of the CT-/MRI+ ischemic strokes were correctly identified at the time of the CT- scan. CONCLUSIONS: Despite a small population and the use of a classifier without the benefit of training on a stroke population, these data suggest that a rapidly acquired, easy-to-use system to assess brain electrical activity at the time of evaluation of acute stroke could be a valuable adjunct to current clinical practice.

Identification of hematomas in mild traumatic brain injury using an index of quantitative brain electrical activity.

Rapid identification of traumatic intracranial hematomas following closed head injury represents a significant health care need because of the potentially life-threatening risk they present. This study demonstrates the clinical utility of an index of brain electrical activity used to identify intracranial hematomas in traumatic brain injury (TBI) presenting to the emergency department (ED). Brain electrical activity was recorded from a limited montage located on the forehead of 394 closed head injured patients who were referred for CT scans as part of their standard ED assessment. A total of 116 of these patients were found to be CT positive (CT+), of which 46 patients with traumatic intracranial hematomas (CT+) were identified for study. A total of 278 patients were found to be CT negative (CT-) and were used as controls. CT scans were subjected to quantitative measurements of volume of blood and distance of bleed from recording electrodes by blinded independent experts, implementing a validated method for hematoma measurement. Using an algorithm based on brain electrical activity developed on a large independent cohort of TBI patients and controls (TBI-Index), patients were classified as either positive or negative for structural brain injury. Sensitivity to hematomas was found to be 95.7% (95% CI = 85.2, 99.5), specificity was 43.9% (95% CI = 38.0, 49.9). There was no significant relationship between the TBI-Index and distance of the bleed from recording sites (F = 0.044, p = 0.833), or volume of blood measured F = 0.179, p = 0.674). Results of this study are a validation and extension of previously published retrospective findings in an independent population, and provide evidence that a TBI-Index for structural brain injury is a highly sensitive measure for the detection of potentially life-threatening traumatic intracranial hematomas, and could contribute to the rapid, quantitative evaluation and treatment of such patients.

Classification algorithms for the identification of structural injury in TBI using brain electrical activity.

BACKGROUND: There is an urgent need for objective criteria adjunctive to standard clinical assessment of acute Traumatic Brain Injury (TBI). Details of the development of a quantitative index to identify structural brain injury based on brain electrical activity will be described. METHODS: Acute closed head injured and normal patients (n=1470) were recruited from 16 US Emergency Departments and evaluated using brain electrical activity (EEG) recorded from forehead electrodes. Patients had high GCS (median=15), and most presented with low suspicion of brain injury. Patients were divided into a CT positive (CT+) group and a group with CT negative findings or where CT scans were not ordered according to standard assessment (CT-/CT_NR). Three different classifier methodologies, Ensemble Harmony, Least Absolute Shrinkage and Selection Operator (LASSO), and Genetic Algorithm (GA), were utilized. RESULTS: Similar performance accuracy was obtained for all three methodologies with an average sensitivity/specificity of 97.5%/59.5%, area under the curves (AUC) of 0.90 and average Negative Predictive Validity (NPV)>99%. Sensitivity was highest for CT+ cases with potentially life threatening hematomas, where two of three classifiers were 100%. CONCLUSION: Similar performance of these classifiers suggests that the optimal separation of the populations was obtained given the overlap of the underlying distributions of features of brain activity. High sensitivity to CT+ injuries (highest in hematomas) and specificity significantly higher than that obtained using ED guidelines for imaging, supports the enhanced clinical utility of this technology and suggests the potential role in the objective, rapid and more optimal triage of TBI patients.

Use of brain electrical activity for the identification of hematomas in mild traumatic brain injury.

This study investigates the potential clinical utility in the emergency department (ED) of an index of brain electrical activity to identify intracranial hematomas. The relationship between this index and depth, size, and type of hematoma was explored. Ten minutes of brain electrical activity was recorded from a limited montage in 38 adult patients with traumatic hematomas (CT scan positive) and 38 mild head injured controls (CT scan negative) in the ED. The volume of blood and distance from recording electrodes were measured by blinded independent experts. Brain electrical activity data were submitted to a classification algorithm independently developed traumatic brain injury (TBI) index to identify the probability of a CT+traumatic event. There was no significant relationship between the TBI-Index and type of hematoma, or distance of the bleed from recording sites. A significant correlation was found between TBI-Index and blood volume. The sensitivity to hematomas was 100%, positive predictive value was 74.5%, and positive likelihood ratio was 2.92. The TBI-Index, derived from brain electrical activity, demonstrates high accuracy for identification of traumatic hematomas. Further, this was not influenced by distance of the bleed from the recording electrodes, blood volume, or type of hematoma. Distance and volume limitations noted with other methods, (such as that based on near-infrared spectroscopy) were not found, thus suggesting the TBI-Index to be a potentially important adjunct to acute assessment of head injury. Because of the life-threatening risk of undetected hematomas (false negatives), specificity was permitted to be lower, 66%, in exchange for extremely high sensitivity.