Thomas W. McAllister

Brain activation during working memory 1 month after mild traumatic brain injury : A functional MRI study

Objective: To assess patterns of regional brain activation in response to varying working memory loads shortly after mild traumatic brain injury (MTBI). Background: Many individuals complain of memory difficulty shortly after MTBI. Memory performance in these individuals can be normal despite these complaints. Methods: Brain activation patterns in response to a working memory task (auditory n-back) were assessed with functional MRI in 12 MTBI patients within 1 month of their injury and in 11 healthy control subjects. Results: Brain activation patterns differed between MTBI patients and control subjects in response to increasing working memory processing loads. Maximum intensity projections of statistical parametric maps in control subjects showed bifrontal and biparietal activation in response to a low processing load, with little additional increase in activation associated with the high load task. MTBI patients showed some activation during the low processing load task but significantly increased activation during the high load condition, particularly in the right parietal and right dorsolateral frontal regions. Task performance did not differ significantly between groups. Conclusion: MTBI patients differed from control subjects in activation pattern of working memory circuitry in response to different processing loads, despite similar task performance. This suggests that injury-related changes in ability to activate or to modulate working memory processing resources may underlie some of the memory complaints after MTBI.

Frequency and Location of Head Impact Exposures in Individual Collegiate Football Players

CONTEXT Measuring head impact exposure is a critical step toward understanding the mechanism and prevention of sport-related mild traumatic brain (concussion) injury, as well as the possible effects of repeated subconcussive impacts. OBJECTIVE To quantify the frequency and location of head impacts that individual players received in 1 season among 3 collegiate teams, between practice and game sessions, and among player positions. DESIGN Cohort study. SETTING Collegiate football field. PATIENTS OR OTHER PARTICIPANTS One hundred eighty-eight players from 3 National Collegiate Athletic Association football teams. INTERVENTION(S) Participants wore football helmets instrumented with an accelerometer-based system during the 2007 fall season. MAIN OUTCOME MEASURE(S) The number of head impacts greater than 10 g and location of the impacts on the players helmet were recorded and analyzed for trends and interactions among teams (A, B, or C), session types, and player positions using Kaplan-Meier survival curves. RESULTS The total number of impacts players received was nonnormally distributed and varied by team, session type, and player position. The maximum number of head impacts for a single player on each team was 1022 (team A), 1412 (team B), and 1444 (team C). The median number of head impacts on each team was 4.8 (team A), 7.5 (team B), and 6.6 (team C) impacts per practice and 12.1 (team A), 14.6 (team B), and 16.3 (team C) impacts per game. Linemen and linebackers had the largest number of impacts per practice and per game. Offensive linemen had a higher percentage of impacts to the front than to the back of the helmet, whereas quarterbacks had a higher percentage to the back than to the front of the helmet. CONCLUSIONS The frequency of head impacts and the location on the helmet where the impacts occur are functions of player position and session type. These data provide a basis for quantifying specific head impact exposure for studies related to understanding the biomechanics and clinical aspects of concussion injury, as well as the possible effects of repeated subconcussive impacts in football.

Exploring the convergence of posttraumatic stress disorder and mild traumatic brain injury.

The authors examine the relationship of the two signature injuries experienced by military personnel serving in Afghanistan and Iraq: posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mild TBI). Studies show that a substantial minority of those serving develop persistent emotional sequelae (such as PTSD and other psychological health problems) and/or somatic or cognitive sequelae (postconcussive symptoms) of traumatic exposure. Remarkably, the mechanism (emotional versus biomechanical) and locus (head versus other regions) of injury are weak determinants of whether an individual develops PTSD, persistent postconcussive symptoms, or both. Preexisting or traumatically acquired cognitive dysfunction can increase the risk for these syndromes, probably by reducing cognitive reserve. Structural and functional neuroimaging studies can be interpreted to explain part of the shared symptomatic and functional variance in these syndromes, but this literature is far from consistent and serves mainly to raise new, challenging questions about mutual pathophysiology. The frequent confluence of PTSD and persistent postconcussive symptoms in military personnel strains the bounds of these constructs. New studies are needed to improve our understanding of how emotional and biomechanical stressors can yield these adverse outcomes and how such outcomes can be prevented and treated.

An integrated review of recovery after mild traumatic brain injury (MTBI): implications for clinical management.

The diagnosis and treatment of mild traumatic brain injury (MTBI)have historically been hampered by an incomplete base of scientific evidence to guide clinicians. One question has been most elusive to clinicians and researchers alike: What is the true natural history of MTBI? Fortunately, the science of MTBI has advanced more in the last decade than in the previous 50 years, and now reaches a maturity point at which the science can drive an evidence-based approach to clinical management. In particular, technological advances in functional neuroimaging have created a powerful bridge between the clinical and basic science of MTBI in humans. Collectively, findings from clinical, basic science, and functional neuroimaging studies now establish a foundation on which to build integrative theories and testable hypotheses around a comprehensive model of MTBI recovery. We review the current scientific literature on postconcussion symptom recovery, neuropsychological outcome, and neurophysiological healing after MTBI. Special emphasis is placed on how the new evidence base can help guide clinicians in the evaluation and management of military-related MTBI.

Depression and Cognitive Complaints Following Mild Traumatic Brain Injury

Traumatic brain injury (TBI) is a common occurrence with multiple possible neuropsychiatric sequelae, including problems with cognition, emotion, and behavior. While many individuals experience significant improvement over the first months following mild TBI, a nontrivial minority will develop persistent, functionally impairing post-TBI symptoms. Depression and cognitive impairment are among the most common such symptoms, and they may respond to a combination of rehabilitative and pharmacologic treatments. This article discusses the clinical approach to treating an individual with depression and cognitive complaints following mild TBI. Recommendations regarding the diagnosis, evaluation, and treatment of these problems are offered.

Head impact exposure in collegiate football players

In American football, impacts to the helmet and the resulting head accelerations are the primary cause of concussion injury and potentially chronic brain injury. The purpose of this study was to quantify exposures to impacts to the head (frequency, location and magnitude) for individual collegiate football players and to investigate differences in head impact exposure by player position. A total of 314 players were enrolled at three institutions and 286,636 head impacts were recorded over three seasons. The 95th percentile peak linear and rotational acceleration and HITsp (a composite severity measure) were 62.7g, 4378rad/s(2) and 32.6, respectively. These exposure measures as well as the frequency of impacts varied significantly by player position and by helmet impact location. Running backs (RB) and quarter backs (QB) received the greatest magnitude head impacts, while defensive line (DL), offensive line (OL) and line backers (LB) received the most frequent head impacts (more than twice as many than any other position). Impacts to the top of the helmet had the lowest peak rotational acceleration (2387rad/s(2)), but the greatest peak linear acceleration (72.4g), and were the least frequent of all locations (13.7%) among all positions. OL and QB had the highest (49.2%) and the lowest (23.7%) frequency, respectively, of front impacts. QB received the greatest magnitude (70.8g and 5428rad/s(2)) and the most frequent (44% and 38.9%) impacts to the back of the helmet. This study quantified head impact exposure in collegiate football, providing data that is critical to advancing the understanding of the biomechanics of concussive injuries and sub-concussive head impacts.

Cognitive effects of one season of head impacts in a cohort of collegiate contact sport athletes

Objective: To determine whether exposure to repetitive head impacts over a single season negatively affects cognitive performance in collegiate contact sport athletes. Methods: This is a prospective cohort study at 3 Division I National Collegiate Athletic Association athletic programs. Participants were 214 Division I college varsity football and ice hockey players who wore instrumented helmets that recorded the acceleration-time history of the head following impact, and 45 noncontact sport athletes. All athletes were assessed prior to and shortly after the season with a cognitive screening battery (ImPACT) and a subgroup of athletes also were assessed with 7 measures from a neuropsychological test battery. Results: Few cognitive differences were found between the athlete groups at the preseason or postseason assessments. However, a higher percentage of the contact sport athletes performed more poorly than predicted postseason on a measure of new learning (California Verbal Learning Test) compared to the noncontact athletes (24% vs 3.6%; p < 0.006). On 2 postseason cognitive measures (ImPACT Reaction Time and Trails 4/B), poorer performance was significantly associated with higher scores on several head impact exposure metrics. Conclusion: Repetitive head impacts over the course of a single season may negatively impact learning in some collegiate athletes. Further work is needed to assess whether such effects are short term or persistent.

Regional brain atrophy in cognitively intact adults with a single APOE ε4 allele

Objective: To determine whether cognitively intact adults with the APOE ε3/ε4 genotype show reduced gray matter density on voxel-based morphometry (VBM) vs those homozygous for the ε3 allele. Methods: Participants were healthy, cognitively intact, right-handed adults, age 19 to 80, who completed genotyping, neuropsychological testing, and MRI. Forty-nine participants had the ε3/ε3 genotype and 27 had the ε3/ε4 genotype. Gray matter data were analyzed using the general linear model as implemented in the Statistical Parametric Mapping package, adjusting for age and sex. Results: The ε3/ε4 participants showed lower gray matter density than the ε3/ε3 participants in right medial temporal and bilateral frontotemporal regions as well as other areas. There were no regions in which ε3/ε4 participants showed higher gray matter density than ε3/ε3 participants. Conclusions: Regionally reduced gray matter density is detectable in cognitively intact adults with a single copy of the APOE ε4 allele.

The Relationship between fMRI Activation and Cerebral Atrophy: Comparison of Normal Aging and Alzheimer Disease

Functional MRI has recently been used to examine activation associated with aging and dementia, yet little is known regarding the effect of cerebral atrophy on fMRI signal. The purpose of this study was to examine the relationship between measures of global and regionally specific atrophy and fMRI activation in normal aging and in Alzheimer disease (AD). Two groups of subjects were studied with echoplanar imaging and quantitative structural volumetry: healthy controls spanning a broad age and atrophy range (n = 16) and patients with mild AD (n = 8). Results from a semantic task previously found to activate left inferior frontal (LIFG) and left superior temporal (LSTG) gyri were analyzed. The correlations between clusters of activation in the LIFG and LSTG and measures of local atrophy in the LIFG and LSTG regions were evaluated. For control subjects, there was no significant correlation between activation and regional or total brain atrophy (for LIFG r = -0.03, NS; for LSTG r = 0.20, NS). In contrast, for AD patients, there was a significant positive correlation between atrophy and activation in LIFG (r = 0.70, P = 0.05) but not LSTG (r = 0.00, NS). These results suggest that activation of language regions and atrophy within those regions may be independent among healthy adults spanning a broad age and atrophy range. However, in AD, a relationship exists in the LIFG that may reflect compensatory recruitment of cortical units or disease-specific changes in the hemodynamic response.

Neuroimaging findings in mild traumatic brain injury

The role of neuroimaging in the diagnosis and management of mild traumatic brain injury (TBI) is evolving. In general, the structural imaging techniques play a role in acute diagnosis and management, while the functional imaging techniques show promise for clarification of pathophysiology, symptom genesis, and mechanisms of recovery. A wide array of neuropathological processes are involved in mild TBI including changes in bone (e.g., a skull fracture), tissue density and water content (edema), blood flow, white matter integrity and pathway connectivity (diffuse axonal injury), and subtle changes in the neuronal and extracellular biochemical milieu. No single imaging technique is capable of addressing all these processes. It is, therefore, important to be aware of the advantages and limitations of the various available imaging modalities. This paper selectively reviews the pertinent literature on the structural and functional imaging in mild TBI.