Angela I. Drake

Integrated imaging approach with MEG and DTI to detect mild traumatic brain injury in military and civilian patients.

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild (and some moderate) TBI can be difficult to diagnose due to lack of obvious external injuries and because the injuries are often not visible on conventional acute MRI or CT. Injured brain tissues in TBI patients generate pathological low-frequency neuronal magnetic signal (delta waves 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). We hypothesize that abnormal MEG delta waves originate from gray matter neurons that experience de-afferentation due to axonal injury to the underlying white matter fiber tracts, which is manifested on diffusion tensor imaging (DTI) as reduced fractional anisotropy. The present study used a neuroimaging approach integrating findings of magnetoencephalography (MEG) and diffusion tensor imaging (DTI), evaluating their utility in diagnosing mild TBI in 10 subjects in whom conventional CT and MRI showed no visible lesions in 9. The results show: (1) the integrated approach with MEG and DTI is more sensitive than conventional CT and MRI in detecting subtle neuronal injury in mild TBI; (2) MEG slow waves in mild TBI patients originate from cortical gray matter areas that experience de-afferentation due to axonal injuries in the white matter fibers with reduced fractional anisotropy; (3) findings from the integrated imaging approach are consistent with post-concussive symptoms; (4) in some cases, abnormal MEG delta waves were observed in subjects without obvious DTI abnormality, indicating that MEG may be more sensitive than DTI in diagnosing mild TBI.

Factors predicting return to work following mild traumatic brain injury: a discriminant analysis.

Studies of mild traumatic brain injury (MTBI) suggest that most individuals recover rapidly and return to their everyday activities. However, a percentage of MTBI patients report persistent problems with cognitive, physical, and emotional symptoms. There is also evidence that some experience changes in occupational functioning following MTBI. The current study used a stepwise discriminant function analysis (DFA) to examine the role of injury severity variables, cognitive performance, and ratings of symptoms of TBI in predicting work status following MTBI. Subjects included 121 MTBI patients who were all active-duty military personnel. The stepwise DFA revealed that age and three cognitive variables (verbal memory, verbal fluency, and a speed test of planning and strategy) were predictive of work status 3–15 months following a documented MTBI, correctly classifying work status 68.8% of the time. A cross-validation DFA was conducted, with a 66.1% correct classification rate. These findings highlight the importance of cognitive impairments in identifying those at risk for occupational impairment following MTBI.

An automatic MEG low-frequency source imaging approach for detecting injuries in mild and moderate TBI patients with blast and non-blast causes

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. Injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). We developed a new automated MEG low-frequency source imaging method and applied this method in 45 mild TBI (23 from combat-related blasts, and 22 from non-blast causes) and 10 moderate TBI patients (non-blast causes). Seventeen of the patients with mild TBI from blasts had tertiary injuries resulting from the blast. The results show our method detected abnormalities at the rates of 87% for the mild TBI group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities were 96% and 77% for the blast and non-blast TBI groups, respectively. The spatial characteristics of abnormal slow-wave generation measured by Z scores in the mild blast TBI group significantly correlated with those in non-blast mild TBI group. Among 96 cortical regions, the likelihood of abnormal slow-wave generation was less in the mild TBI patients with blast than in the mild non-blast TBI patients, suggesting possible protective effects due to the military helmet and armor. Finally, the number of cortical regions that generated abnormal slow-waves correlated significantly with the total post-concussive symptom scores in TBI patients. This study provides a foundation for using MEG low-frequency source imaging to support the clinical diagnosis of TBI.

Apolipoprotein E and traumatic brain injury in a military population: evidence of a neuropsychological compensatory mechanism?

Objective: Although research has implicated the apolipoprotein E (APOE) epsilon-4 genotype as having a negative effect on neuropsychological outcomes following traumatic brain injury (TBI), the potentially negative role of the ε4 allele on TBI outcomes has recently been challenged. In light of this debate, the present study served to examine the role of APOE genotype on neuropsychological outcomes approximately 1 month following mild to moderate TBI in a military population. Because of the well documented role of the APOE-ε4 allele in increasing the risk of Alzheimer’s disease, we predicted that persons with the APOE-ε4 genotype would display relatively greater deficits in cognition than their non-ε4 counterparts. Methods: 78 participants were consecutively recruited following a mild to moderate TBI and were divided into two groups based on the presence or absence of an APOE ε4 allele. Groups were comparable on demographic characteristics and psychosocial outcomes. Participants were administered a comprehensive neuropsychological battery. Results: Analyses revealed comparable performances on most neuropsychological measures and better performances by ε4 carriers on select measures of attention, executive functioning and episodic memory encoding. Furthermore, differences remained after accounting for the effects of TBI severity. Conclusions: Evidence from these analyses supports current literature refuting the notion of relatively poorer neuropsychological functioning associated with the APOE-ε4 genotype among young adult participants shortly following mild or moderate brain injury. Neuropsychological performance differences by APOE genotype following TBI are discussed in terms of the importance of considering severity of injury, timing of postinjury assessment and possible neurocognitive compensatory mechanisms.

Objective Vestibular Tests as Outcome Measures in Head Injury Patients

Hypothesis: Dynamic visual acuity testing (DVAT) and the Dizziness Handicap Index (DHI) can be used as reliable outcome measures in patients after head injury. Background: Balance disorders are a significant disability after mild traumatic brain injury (TBI). Assessing when individuals can perform activities of daily living, return to work, and begin to play sports can be difficult to determine. Objective outcome measures that correlate with successful life skills can be useful in managing these patients. Methods: Fifty‐three active duty individuals who suffered mild TBI underwent weekly DVAT testing and were administered a weekly DHI. Results in this group were compared with 46 control subjects who had not experienced TBI. In addition, weekly scores were compared with the patients functional level, time to return to work, and time to perform all job related activities. Results: Individuals with TBI showed an overall increase of 42% in DVAT function over the first 4 weeks of testing, whereas controls showed an 8% increase. Concurrently, individuals with TBI averaged a 18‐point improvement in DHI function, whereas control subjects showed no significant change in this score. Improvement in DVAT and DHI function correlated closely at the 1‐week time point. Improvement in the patients cognitive function, ability to return to activities of daily living, and ability to return to work gradually improved continuously. Conclusion: DVAT and the DHI can be used as reliable outcome measures in evaluating the progress of patients with balance disorders associated with TBI. These measures allow providers to make more reliable recommendations regarding such activities as returning to work.

Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI) can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1–4 Hz) that can be measured and localized by resting-state magnetoencephalography (MEG). In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1–4 Hz) from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes), our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes), blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI.

MEG source imaging method using fast L1 minimum-norm and its applications to signals with brain noise and human resting-state source amplitude images.

The present study developed a fast MEG source imaging technique based on Fast Vector-based Spatio-Temporal Analysis using a L1-minimum-norm (Fast-VESTAL) and then used the method to obtain the source amplitude images of resting-state magnetoencephalography (MEG) signals for different frequency bands. The Fast-VESTAL technique consists of two steps. First, L1-minimum-norm MEG source images were obtained for the dominant spatial modes of sensor-waveform covariance matrix. Next, accurate source time-courses with millisecond temporal resolution were obtained using an inverse operator constructed from the spatial source images of Step 1. Using simulations, Fast-VESTALs performance was assessed for its 1) ability to localize multiple correlated sources; 2) ability to faithfully recover source time-courses; 3) robustness to different SNR conditions including SNR with negative dB levels; 4) capability to handle correlated brain noise; and 5) statistical maps of MEG source images. An objective pre-whitening method was also developed and integrated with Fast-VESTAL to remove correlated brain noise. Fast-VESTALs performance was then examined in the analysis of human median-nerve MEG responses. The results demonstrated that this method easily distinguished sources in the entire somatosensory network. Next, Fast-VESTAL was applied to obtain the first whole-head MEG source-amplitude images from resting-state signals in 41 healthy control subjects, for all standard frequency bands. Comparisons between resting-state MEG sources images and known neurophysiology were provided. Additionally, in simulations and cases with MEG human responses, the results obtained from using conventional beamformer technique were compared with those from Fast-VESTAL, which highlighted the beamformers problems of signal leaking and distorted source time-courses.

Utility of Glasgow Coma Scale-Extended in symptom prediction following mild traumatic brain injury.

Study objective: To examine the efficacy of the Glasgow Coma Scale-Extended (GCS-E) for the prediction of symptoms commonly associated with mild traumatic brain injury (TBI). Method: Three hundred and sixty-one participants with a mild TBI were evaluated using the GCS-E and the Standardized Assessment of Concussion. A sub-group of 185 participants took part in a more extensive evaluation, which also included measures of depression and vestibular symptoms. All participants had a Glasgow Coma Scale score of 15, but experienced varying lengths of post-traumatic amnesia (PTA) as measured by the GCS-E. Results: Use of the GCS-E for assessment of PTA duration revealed that longer lengths of amnesia following mild TBI were associated with greater incidence of dizziness, depression and cognitive impairments during the first weeks after injury. Conclusion: Results suggest that the GCS-E is a useful tool for the prediction of symptoms associated with mild TBI.

Clinical, cognitive, and genetic predictors of change in job status following traumatic brain injury in a military population

ObjectiveTraumatic brain injury (TBI) is a risk associated with military duty, and residual effects from TBI may adversely affect a service members ability to complete duties. It is, therefore, important to identify factors associated with a change in job status following TBI in an active military population. On the basis of previous research, we predicted that apolipoprotein E (APOE) genotype may be 1 factor. DesignCohort study of military personnel who sustained a mild to moderate TBI. SettingMilitary medical clinics. Patients or Other ParticipantsFifty-two military participants were recruited through the Defense and Veterans Brain Injury Center, affiliated with Naval Medical Center San Diego and the Defense and Veterans Brain Injury Center Concussion Clinic located at the First Marine Division at Camp Pendleton. Intervention(s)A multivariate statistical classification approach called optimal data analysis allowed for consideration of APOE genotype alongside cognitive, emotional, psychosocial, and physical functioning. Main Outcome Measure(s)APOE genotype, neuropsychological, psychosocial, and clinical outcomes. ResultsWe identified a model of factors that was associated with a change in job status among military personnel who experienced a mild or moderate TBI. ConclusionsFactors associated with a change in job status are different when APOE genotype is considered. We conclude that APOE genotype may be an important genetic factor in recovery from mild to moderate head injury.

Routine TBI screening following combat deployments

A precise estimate of the rates of traumatic brain injury (TBI) in returning combat troops is difficult to establish given the challenges of screening large numbers of military personnel returning from combat deployments. The Brief Traumatic Brain Injury Screen (BTBIS) was implemented in the First Marine Expeditionary Force between 2004 and 2006. Nine percent of the 7909 marines who completed the BTBIS were considered having a positive screen; that is, they endorsed at least one injury mechanism and indicated a change in mental status at the time of injury. The majority of combat-related TBIs were due to multiple injury agents with the next largest group related to blast exposure only. Most importantly, of those who screened positive for TBI 70.5% (n=500) were first identified by the screen. Service members who endorsed items on the BTBIS were contacted for follow-up assessment of persistent symptoms related to TBI and clinical referrals were made as needed. Given the rate of positive TBI screens in this non-referred sample of military personnel returning from a combat deployment, routine TBI screening appears valuable in screening individuals who might not be identified otherwise. Furthermore, this study appears to refute the contention that routine TBI screening will result in an over-identification of TBI in this population.