Walter Carr

Decoupling of the brain's default mode network during deep sleep

The recent discovery of a circuit of brain regions that is highly active in the absence of overt behavior has led to a quest for revealing the possible function of this so-called default-mode network (DMN). A very recent study, finding similarities in awake humans and anesthetized primates, has suggested that DMN activity might not simply reflect ongoing conscious mentation but rather a more general form of network dynamics typical of complex systems. Here, by performing functional MRI in humans, it is shown that a natural, sleep-induced reduction of consciousness is reflected in altered correlation between DMN network components, most notably a reduced involvement of frontal cortex. This suggests that DMN may play an important role in the sustenance of conscious awareness.

Comparison of 10 hemostatic dressings in a groin transection model in swine.

BACKGROUND Major improvements have been made in the development of novel dressings with hemostatic properties to control heavy bleeding in noncompressible areas. To test the relative efficacy of different formulations in bleeding control, recently manufactured products need to be compared using a severe injury model. METHODS Ten hemostatic dressings and the standard gauze bandage were tested in anesthetized Yorkshire pigs hemorrhaged by full transection of the femoral vasculature at the level of the groin. Application of these dressings with a 5-minute compression period (at approximately 200 mm Hg) was followed with a subsequent infusion of colloid for a period of 30 minutes. Primary outcomes were survival and amount and incidence of bleeding after dressing application. Vital signs and wound temperature were continuously recorded throughout the 3-hour experimental observation. RESULTS These findings indicated that four dressings were effective in improving bleeding control and superior to the standard gauze bandage. This also correlated with increased survival rates. Absorbent property, flexibility, and the hemostatic agent itself were identified as the critical factors in controlling bleeding on a noncompressible transected vascular and tissue injury. CONCLUSIONS Celox, QuikClot ACS, WoundStat, and X-Sponge ranked superior in terms of low incidence of rebleeding, volume of blood loss, maintenance of mean arterial pressure >40 mm Hg, and survival.

Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from other states of consciousness

Rapid eye movement (REM) sleep constitutes a distinct “third state” of consciousness, during which levels of brain activity are commensurate with wakefulness, but conscious awareness is radically transformed. To characterize the temporal and spatial features of this paradoxical state, we examined functional interactions between brain regions using fMRI resting-state connectivity methods. Supporting the view that the functional integrity of the default mode network (DMN) reflects “level of consciousness,” we observed functional uncoupling of the DMN during deep sleep and recoupling during REM sleep (similar to wakefulness). However, unlike either deep sleep or wakefulness, REM was characterized by a more widespread, temporally dynamic interaction between two major brain systems: unimodal sensorimotor areas and the higher-order association cortices (including the DMN), which normally regulate their activity. During REM, these two systems become anticorrelated and fluctuate rhythmically, in reciprocally alternating multisecond epochs with a frequency ranging from 0.1 to 0.01 Hz. This unique spatiotemporal pattern suggests a model for REM sleep that may be consistent with its role in dream formation and memory consolidation.

Automated Neuropsychological Assessment Metrics: Repeated Assessment with Two Military Samples

INTRODUCTION U.S. military troops deploying to war zones are currently administered the Automated Neuropsychological Assessment Metrics (ANAM4) Traumatic Brain Injury (TBI) Battery to establish individual neurocognitive performance baselines. In part, the utility of the ANAM4 TBI Battery baseline measurement depends on test-retest reliability of this instrument. The purpose of this report was to evaluate performance following multiple administrations of the ANAM4 TBI Battery: does performance in a repeated measures paradigm constitute a stable, interpretable indication of baseline neurocognitive ability? METHODS The data presented here are from the ANAM4 TBI Battery administered four times to a group of U.S. Marines in Study 1 and eight times to a group of New Zealand Defence Force personnel in Study 2. RESULTS The results show practice effect in five of six performance subtests in both Study 1 and Study 2. DISCUSSION Results are consistent with expectations that multiple test sessions are required to reach stable performance on some computerized tasks. These results have implications for taking ANAM4 TBI Battery practice effects into account in test administration and in data interpretation.

ANAM4 TBI Reaction Time-Based Tests have Prognostic Utility for Acute Concussion

The Concussion Restoration Care Center has used the Automated Neuropsychological Assessment Metrics version 4 Traumatic Brain Injury (ANAM4 TBI) battery in clinical assessment of concussion. The studys aim is to evaluate the prognostic utility of the ANAM4 TBI. In 165 concussed active duty personnel (all ultimately returned to duty) seen and tested on the ANAM4 TBI on days 3 and 5 (median times) from their injury, Spearmans ρ statistics showed that all performance subtests (at day 5) were associated with fewer days return-to-duty (RTD) time, whereas concussion history or age did not. Kruskal-Wallis statistics showed that ANAM4 TBI, loss of consciousness, and post-traumatic amnesia were associated with increased RTD time; ANAM4 TBI reaction time-based subtests, collectively, showed the largest effect sizes. A survival analysis using a Kaplan-Meier plot showed that the lowest 25% on the reaction time-based subtests had a median RTD time of 19 days, whereas those in the upper 25% had a median RTD time of approximately 7 days. Results indicate that until validated neurocognitive testing is introduced, the ANAM4 TBI battery, especially reaction time-based tests, has prognostic utility.

Repeated low-level blast exposure: A descriptive human subjects study

The relationship between repeated exposure to blast overpressure and neurological function was examined in the context of breacher training at the U.S. Marine Corps Weapons Training Battalion Dynamic Entry School. During this training, Students are taught to apply explosive charges to achieve rapid ingress into secured buildings. For this study, both Students and Instructors participated in neurobehavioral testing, blood toxin screening, vestibular/auditory testing, and neuroimaging. Volunteers wore instrumentation during training to allow correlation of human response measurements and blast overpressure exposure. The key findings of this study were from high-memory demand tasks and were limited to the Instructors. Specific tests showing blast-related mean differences were California Verbal Learning Test II, Automated Neuropsychological Assessment Metrics subtests (Match-to-Sample, Code Substitution Delayed), and Delayed Matching-to-Sample 10-second delay condition. Importantly, apparent deficits were paralleled with functional magnetic resonance imaging using the n-back task. The findings of this study are suggestive, but not conclusive, owing to small sample size and effect. The observed changes yield descriptive evidence for potential neurological alterations in the subset of individuals with occupational history of repetitive blast exposure. This is the first study to integrate subject instrumentation for measurement of individual blast pressure exposure, neurocognitive testing, and neuroimaging.

Relation of repeated low-level blast exposure with symptomology similar to concussion.

Objective:To investigate anecdotal reports suggesting that repeated exposure to low-level explosive blast has myriad health impacts, including an array of neurological effects. Participants:A total of 184 anonymous survey respondents from military and nonmilitary law enforcement populations (135 exposed to occupational blast and 49 controls). Design:Survey of self-reported history of occupational exposure to repeated low-level blast (breaching blast) and symptomology similar to concussion. Results:Findings suggest that number and severity of symptoms increase with history of chronic blast exposure (F = 18.26, P < .001) and that symptoms can interfere with daily activity (t = 2.60, P = .010). Conclusion:Given the prevalence of repeated exposure to blast among some military and civilian law enforcement occupations, the results of this survey study support a role for blast surveillance programs as well as continued research on health impacts of low-level repeated blast exposure.

Ubiquitin carboxy-terminal hydrolase-l1 as a serum neurotrauma biomarker for exposure to occupational low-level blast.

Repeated exposure to low-level blast is a characteristic of a few select occupations and there is concern that such occupational exposures present risk for traumatic brain injury. These occupations include specialized military and law enforcement units that employ controlled detonation of explosive charges for the purpose of tactical entry into secured structures. The concern for negative effects from blast exposure is based on rates of operator self-reported headache, sleep disturbance, working memory impairment, and other concussion-like symptoms. A challenge in research on this topic has been the need for improved assessment tools to empirically evaluate the risk associated with repeated exposure to blast overpressure levels commonly considered to be too low in magnitude to cause acute injury. Evaluation of serum-based neurotrauma biomarkers provides an objective measure that is logistically feasible for use in field training environments. Among candidate biomarkers, ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) has some empirical support and was evaluated in this study. We used daily blood draws to examine acute change in UCH-L1 among 108 healthy military personnel who were exposed to repeated low-level blast across a 2-week period. These research volunteers also wore pressure sensors to record blast exposures, wrist actigraphs to monitor sleep patterns, and completed daily behavioral assessments of symptomology, postural stability, and neurocognitive function. UCH-L1 levels were elevated as a function of participating in the 2-week training with explosives, but the correlation of UCH-L1 elevation and blast magnitude was weak and inconsistent. Also, UCH-L1 elevations did not correlate with deficits in behavioral measures. These results provide some support for including UCH-L1 as a measure of central nervous system effects from exposure to low-level blast. However, the weak relation observed suggests that additional indicators of blast effect are needed.

Moderate blast exposure results in increased IL-6 and TNFα in peripheral blood

A unique cohort of military personnel exposed to isolated blast was studied to explore acute peripheral cytokine levels, with the aim of identifying blast-specific biomarkers. Several cytokines, including interleukin (IL) 6, IL-10 and tumor necrosis factor alpha (TNFα) have been linked to pre-clinical blast exposure, but remained unstudied in clinical blast exposure. To address this gap, blood samples from 62 military personnel were obtained at baseline, and daily, during a 10-day blast-related training program; changes in the peripheral concentrations of IL-6, IL-10 and TNFα were evaluated using an ultrasensitive assay. Two groups of trainees were matched on age, duration of military service, and previous history of blast exposure(s), resulting in moderate blast cases and no/low blast controls. Blast exposures were measured using helmet sensors that determined the average peak pressure in pounds per square inch (psi). Moderate blast cases had significantly elevated concentrations of IL-6 (F1,60=18.81, p<0.01) and TNFα (F1,60=12.03, p<0.01) compared to no/low blast controls; levels rebounded to baseline levels the day after blast. On the day of the moderate blast exposure, the extent of the overpressure (psi) in those exposed correlated with IL-6 (r=0.46, p<0.05) concentrations. These findings indicate that moderate primary blast exposure results in changes, specifically acute and transient increases in peripheral inflammatory markers which may have implications for neuronal health.

The natural history of acute recovery of blast-induced mild traumatic brain injury: a case series during war

Traumatic brain injury (TBI) secondary to blast exposure is a common injury in the Global War on Terrorism, but little is known about the acute effects, recovery, pathophysiology, and neuropathology of blast-induced mild TBI (mTBI) in humans in a battlefield environment. Moreover, there is ongoing debate whether blast-induced mTBI is a different injury with a unique pathophysiology compared with mTBI from blunt trauma. In the case series reported here from Craig Joint Theater Hospital at Bagram Airfield, Afghanistan, 15 military service members with acute concussion/mTBI associated with blast exposure were evaluated within the first 24 hours after concussion and on days 2, 3, 5, and 7 with a Graded Symptom Checklist and a balance assessment, the Balance Error Scoring System. These data suggest that the recovery in blast-induced mTBI follows the pattern of recovery in sports-related concussion reported in The National Collegiate Athletic Association Concussion Study. In this retrospective case series, we provide the first description of the natural history of acute recovery in blast-induced mTBI, and we suspect, given our experience treating military service members, that further observations of the natural history of recovery in blast-induced mTBI will continue to mirror the natural history of recovery in sports concussion.