Methodology of the INVestigating traIning assoCiated blasT pAthology (INVICTA) study.

BACKGROUND: Subconcussive blast exposure during military training has been the subject of both anecdotal concerns and reports in the medical literature, but prior studies have often been small and have used inconsistent methods. METHODS: This paper presents the methodology employed in INVestigating traIning assoCiated blasT pAthology (INVICTA) to assess a wide range of aspects of brain function, including immediate and delayed recall, gait and balance, audiologic and oculomotor function, cerebral blood flow, brain electrical activity and neuroimaging and blood biomarkers. RESULTS: A number of the methods employed in INVICTA are relatively easy to reproducibly utilize, and can be completed efficiently, while other measures require greater technical expertise, take longer to complete, or may have logistical challenges. CONCLUSIONS: This presentation of methods used to assess the impact of blast exposure on the brain is intended to facilitate greater uniformity of data collection in this setting, which would enable comparison between different types of blast exposure and environmental circumstances, as well as to facilitate meta-analyses and syntheses across studies.

Fast-Running Tools for Personalized Monitoring of Blast Exposure in Military Training and Operations.

INTRODUCTION: During training and combat operations, military personnel may be exposed to repetitive low-level blast while using explosives to gain entry or by firing heavy weapon systems such as recoilless weapons and high-caliber sniper rifles. This repeated exposure, even within allowable limits, has been associated with cognitive deficits similar to that of accidental and sports concussion such as delayed verbal memory, visual-spatial memory, and executive function. This article presents a novel framework for accurate calculation of the human body blast exposure in military heavy weapon training scenarios using data from the free-field and warfighter wearable pressure sensors. MATERIALS AND METHODS: The CoBi human body model generator tools were used to reconstruct multiple training scenes with different weapon systems. The CoBi Blast tools were used to develop the weapon signature and estimate blast overpressure exposure. The authors have used data from the free-field and wearable pressure sensors to evaluate the framework. RESULTS: Carl-Gustav and 0.50 caliber sniper training scenarios were used to demonstrate and validate the developed framework. These simulations can calculate spatially and temporally resolved blast loads on the whole human body and on specific organs vulnerable to blast loads, such as head, face, and lungs. CONCLUSIONS: This framework has numerous advantages including easier model setup and shorter simulation times. The framework is an important step towards developing an advanced field-applicable technology to monitor low-level blast exposure during heavy weapon military training and combat scenarios.

Assessing a Blast-Related Biomarker in an Operational Community: Glial Fibrillary Acidic Protein in Experienced Breachers.

Mild traumatic brain injury (mTBI) is a risk for military personnel due to blast overpressures, which may result from a variety of sources, including artillery and improvised explosive devices. Much research has gone into the search for a biomarker to identify patients with a TBI. The FDA recently identified two proteins, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1), as biomarkers to evaluate suspected brain injury. Our group previously observed changes in UCH-L1 in a military population exposed to repeated blast. In our current study we assessed GFAP protein levels in a military population exposed to repeated blast during a 2-week training protocol. We observed GFAP levels were reduced in the moderate blast cases on days 6 and 7 during the training. Specifically, moderate blast cases showed a 24.07% reduction from baseline on day 6 and a 29.61% reduction on day 7. Further, GFAP levels were negatively correlated with cumulative blast experienced during training and with duration of military service. We observed that repeated blast exposure at low levels may impact acute changes in GFAP. Additionally subacute cumulative blast exposure or duration of service was also a factor in influencing GFAP levels.

Neurocognitive Performance Deficits Related to Immediate and Acute Blast Overpressure Exposure.

Addressing the concerns surrounding blast injury for the military community is a pressing matter. Specifically, sub-concussive blast effects, or those blast effects which do not yield a medical diagnosis but can result in symptom reporting and negative self-reported outcomes, are becoming increasingly important. This work evaluates explosive blast overpressure and impulse effects at the sub-concussive level on neurocognitive performance assessed with the Defense Automated Neurobehavioral Assessment (DANA) across seven breacher training courses conducted by the US Military. The results reported here come from 202 healthy, male military volunteer participants. Findings indicate that the neurocognitive task appearing most sensitive to identifying performance change is the DANA Procedural Reaction Time (PRT) subtask which may involve a sufficient level of challenge to reliably detect a small, transient cognitive impairment among a healthy undiagnosed population. The blast characteristic that was consistently associated with performance change was peak overpressure. Overall, this study provides evidence that increasing blast overpressure, defined as peak overpressure experienced in a training day, can lead to transient degradations in neurocognitive performance as seen on the DANA PRT subtask, which may generalize to other capabilities.

Decreased connectivity between the thalamus and the neocortex during human nonrapid eye movement sleep.

STUDY OBJECTIVES: To determine whether thalamocortical signaling between the thalamus and the neocortex decreases from wakefulness to nonrapid eye movement (NREM) sleep. DESIGN: Electroencephalography and functional magnetic resonance imaging data were collected simultaneously at 02:30 after 44 h of sleep deprivation. SETTING: Clinical research hospital. PARTICIPANTS: There were six volunteers (mean age 24.2 y, one male) who yielded sufficient amounts of usable, artifact-free data. All were healthy, right-handed native English speakers who consumed less than 710 mL of caffeinated beverages per day. Psychiatric, neurological, circadian, and sleep disorders were ruled out by reviewing each patient's clinical history. A standard clinical nocturnal polysomnogram was negative for sleep disorders. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: A functional connectivity analysis was performed using the centromedian nucleus as the seed region. We determined the statistical significance of the difference between correlations obtained during wakefulness and during slow wave sleep. Neocortical regions displaying decreased thalamic connectivity were all heteromodal regions (e.g., medial frontal gyrus and posterior cingulate/precuneus), whereas there was a complete absence of neocortical regions displaying increased thalamic connectivity. Although more clusters of significant decreases were observed in stage 2 sleep, these results were similar to the results for slow wave sleep. CONCLUSIONS: Results of this study provide evidence of a functional deafferentation of the neocortex during nonrapid eye movement (NREM) sleep in humans. This deafferentation likely accounts for increased sensory awareness thresholds during NREM sleep. Decreased thalamocortical connectivity in regions such as the posterior cingulate/precuneus also are observed in coma and general anesthesia, suggesting that changes in thalamocortical connectivity may act as a universal "control switch" for changes in consciousness that are observed in coma, general anesthesia, and natural sleep.

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.

Infraslow EEG oscillations organize large-scale cortical-subcortical interactions during sleep: a combined EEG/fMRI study.

Infraslow (<0.1 Hz) oscillations of brain activity, measured by EEG and other methods, have become a subject of increasing interest. While their prominence during sleep has been established, the functional significance of these oscillations for sleep physiology is unknown. To clarify this role, we examined correlations between infraslow EEG oscillations and BOLD fMRI during the course of natural sleep in healthy volunteers. Infraslow EEG oscillations appear to organize a broad dissociation of activity in cortical and subcortical regions: in general, correlations between power in the infraslow EEG band and BOLD were positive in subcortical regions and negative in the cortex. Robust negative correlations were found principally in paramedian heteromodal cortices whereas positive correlations were seen in cerebellum, thalamus, basal ganglia, lateral neocortices and hippocampus. This pattern of correlations suggests a mechanism by which infraslow oscillations may organize sleep-dependent neuroplastic processes including consolidation of episodic memory.

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.

fMRI differences between early and late stage-1 sleep.

This study sought to test for differences in regional brain activity between stage-1 sleep immediately following wake and immediately preceding stage-2 sleep. Data were collected during daytime fMRI sessions with simultaneous EEG acquisition. A stage-1 interval was defined as follows: > or =30s of wake, immediately followed by > or =60s of continuous stage 1, immediately followed by > or =30s of stage 2. We compared brain activity between the first 30s of stage 1 (early stage 1), the last 30s of stage 1 (late stage 1), and isolated wake. A conjunction analysis sorted each voxel into one of a series of mutually exclusive categories that represented the various possible combinations of a significant increase, decrease, or no difference among these three states. The initial dataset consisted of 14 healthy volunteers. A total of 22 sessions in these participants yielded six stage-1 intervals (from four participants) that met criteria for inclusion in the analysis. There were multiple clusters of significant voxels. Examples include changes in default-mode network areas where activity increased compared to wake only in early stage 1 and a bilateral change in the hippocampus where activity increased compared to wake only in late stage 1. These results suggest that activity in anatomically identifiable, volumetric brain regions exhibit differences during stage-1 sleep that would not have been detected with the EEG. These differences may also have specific relevance to understanding the process of sleep onset as well as the neural mechanisms of performance lapses during sleep deprivation.