Matched-pair hybrid test paradigm for behind armor blunt trauma using an experimental animal model.

Background: The current behind armor blunt trauma (BABT) injury criterion uses a single penetration limit of 44 mm in Roma Plastilina clay and is not specific to thoracoabdominal regions. However, different regions in the human body have different injury tolerances. This manuscript presents a matched-pair hybrid test paradigm with different experimental models and candidate metrics to develop regional human injury criteria. Methods: Live and cadaver swine were used as matched pair experimental models. An impactor simulating backface deformation profiles produced by body armor from military-relevant ballistics was used to deliver BABT loading to liver and lung regions in cadaver and live swine. Impact loading was characterized using peak accelerations and energy. For live swine, physiological parameters were monitored for 6 hours, animals were euthanized, and a detailed necropsy was done to identify injuries to skeletal structures, organs and soft tissues. A similar process was used to identify injuries to the cadaver swine for targeted thoracoabdominal regions. Results: Two cadavers and one live swine were subjected to BABT impacts to the liver. One cadaver and one live swine were subjected to BABT impacts to the left lung. Injuries to both regions were similar at similar energies between the cadaver and live models. Conclusions: Swine is an established animal for thoracoabdominal impact studies in automotive standards, although at lower insult levels. Similarities in BABT responses between cadaver and live swine allow for extending testing protocols to human cadavers and for the development of scaling relationships between animal and human cadavers, acting as a hybrid protocol between species and live and cadaver models. Injury tolerances and injury risk curves from live animals can be converted to human tolerances via structural scaling using these outcomes. The present experimental paradigm can be used to develop region-based BABT injury criteria, which are not currently available.

Cortical reactivations predict future sensory responses.

Many theories of offline memory consolidation posit that the pattern of neurons activated during a salient sensory experience will be faithfully reactivated, thereby stabilizing the pattern1,2. However, sensory-evoked patterns are not stable but, instead, drift across repeated experiences3-6. Here, to investigate the relationship between reactivations and the drift of sensory representations, we imaged the calcium activity of thousands of excitatory neurons in the mouse lateral visual cortex. During the minute after a visual stimulus, we observed transient, stimulus-specific reactivations, often coupled with hippocampal sharp-wave ripples. Stimulus-specific reactivations were abolished by local cortical silencing during the preceding stimulus. Reactivations early in a session systematically differed from the pattern evoked by the previous stimulus-they were more similar to future stimulus response patterns, thereby predicting both within-day and across-day representational drift. In particular, neurons that participated proportionally more or less in early stimulus reactivations than in stimulus response patterns gradually increased or decreased their future stimulus responses, respectively. Indeed, we could accurately predict future changes in stimulus responses and the separation of responses to distinct stimuli using only the rate and content of reactivations. Thus, reactivations may contribute to a gradual drift and separation in sensory cortical response patterns, thereby enhancing sensory discrimination7.

Biofidelity Assessment of the WIAMan Thorax by a Comparative Study With Hybrid III, THOR, and PMHS in Frontal Sled Testing.

The Warrior Injury Assessment Manikin (WIAMan) anthropomorphic test device (ATD) has been originally developed to predict and prevent injuries for occupants in military vehicles, in an underbody blast environment. However, its crash performance and biofidelity of the thoracic region have not been explored. The aim of this study was to determine and evaluate the WIAMan thoracic responses in a typical frontal sled test. The 40 kph frontal sled tests were conducted to quantify the WIAMan thoracic kinematics, chest deflection, and belt loads. Comparative biofidelities of the WIAMan thorax and other surrogates, including postmortem human surrogates (PMHSs), Hybrid III, and test device for human occupant restraint (THOR) ATDs, were assessed under comparable testing conditions. The similarities and differences between WIAMan and the other surrogates were compared and analyzed, including the motion of bilateral shoulders and T1, time histories of chest deflections, and belt loads. The CORrelation and Analysis (CORA) ratings were used to evaluate the correlations of thoracic responses between the ATDs and PMHS. Compared to the PMHS and THOR, the WIAMan experienced a similar level of left shoulder forward excursions. Larger chest deflection was exhibited in WIAMan throughout the whole duration of belt compression. Differences were found in belt loads between subject types. Overall, WIAMan had slightly lower CORA scores but showed comparable overall performance. The overall thoracic responses of WIAMan under the frontal sled test were more compliant than HIII, but still reasonable compared with PMHS and THOR. Comprehensive systematic studies on comparative biofidelity of WIAMan and other surrogates under different impact conditions are expected in future research.

A versatile viral toolkit for functional discovery in the nervous system.

The ability to precisely control transgene expression is essential for basic research and clinical applications. Adeno-associated viruses (AAVs) are non-pathogenic and can be used to drive stable expression in virtually any tissue, cell type, or species, but their limited genomic payload results in a trade-off between the transgenes that can be incorporated and the complexity of the regulatory elements controlling their expression. Resolving these competing imperatives in complex experiments inevitably results in compromises. Here, we assemble an optimized viral toolkit (VTK) that addresses these limitations and allows for efficient combinatorial targeting of cell types. Moreover, their modular design explicitly enables further refinements. We achieve this in compact vectors by integrating structural improvements of AAV vectors with innovative molecular tools. We illustrate the potential of this approach through a systematic demonstration of their utility for targeting cell types and querying their biology using a wide array of genetically encoded tools.

Evaluating the Limits in the Biomechanics of Blunt Lung Injury.

Thoracic blunt trauma is evident in up to one-fifth of all hospital admissions, and is second only to head trauma in motor vehicle crashes. One of the most problematic injury mechanisms associated with blunt thoracic trauma is pulmonary contusion, occurring in up to 75% of blunt thoracic trauma cases. The source and effects of pulmonary contusion caused by blunt lung injury are not well defined, especially within the field of continuum biomechanics. This, paired with unreliable diagnostics for pulmonary contusion, leads to uncertainty in both the clinical entity and mechanics of how to predict the presence of injury. There is a distinct need to combine the clinical aspects with mechanical insights through the identification and mitigation of blunt lung trauma and material testing and modeling. This is achieved through using the mechanical insights of lung tissue behavior in order to better understand the injurious mechanisms and courses of treatment of blunt-caused pulmonary contusion. This paper hopes to act as a step forward in connecting two perspectives of blunt lung injury, the clinical entity, and mechanical testing and modeling, by reviewing the known literature and identifying the unknowns within the two related fields. Through a review of related literature, clinical evidence is correlated to mechanical data to gain a better understanding of what is being missed in identification and response to blunt lung injury as a whole.

Investigating the Association between Motor Function, Neuroinflammation, and Recording Metrics in the Performance of Intracortical Microelectrode Implanted in Motor Cortex.

Long-term reliability of intracortical microelectrodes remains a challenge for increased acceptance and deployment. There are conflicting reports comparing measurements associated with recording quality with postmortem histology, in attempts to better understand failure of intracortical microelectrodes (IMEs). Our group has recently introduced the assessment of motor behavior tasks as another metric to evaluate the effects of IME implantation. We hypothesized that adding the third dimension to our analysis, functional behavior testing, could provide substantial insight on the health of the tissue, success of surgery/implantation, and the long-term performance of the implanted device. Here we present our novel analysis scheme including: (1) the use of numerical formal concept analysis (nFCA) and (2) a regression analysis utilizing modern model/variable selection. The analyses found complimentary relationships between the variables. The histological variables for glial cell activation had associations between each other, as well as the neuronal density around the electrode interface. The neuronal density had associations to the electrophysiological recordings and some of the motor behavior metrics analyzed. The novel analyses presented herein describe a valuable tool that can be utilized to assess and understand relationships between diverse variables being investigated. These models can be applied to a wide range of ongoing investigations utilizing various devices and therapeutics.

Rodent Behavioral Testing to Assess Functional Deficits Caused by Microelectrode Implantation in the Rat Motor Cortex.

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes demonstrate the ability to record action potentials from individual or small groups of neurons. Such recorded signals have successfully been used to allow patients to interface with or control computers, robotic limbs, and their own limbs. However, previous animal studies have shown that a microelectrode implantation in the brain not only damages the surrounding tissue but can also result in functional deficits. Here, we discuss a series of behavioral tests to quantify potential motor impairments following the implantation of intracortical microelectrodes into the motor cortex of a rat. The methods for open field grid, ladder crossing, and grip strength testing provide valuable information regarding the potential complications resulting from a microelectrode implantation. The results of the behavioral testing are correlated with endpoint histology, providing additional information on the pathological outcomes and impacts of this procedure on the adjacent tissue.

Microelectrode implantation in motor cortex causes fine motor deficit: Implications on potential considerations to Brain Computer Interfacing and Human Augmentation.

Intracortical microelectrodes have shown great success in enabling locked-in patients to interact with computers, robotic limbs, and their own electrically driven limbs. The recent advances have inspired world-wide enthusiasm resulting in billions of dollars invested in federal and industrial sponsorships to understanding the brain for rehabilitative applications. Additionally, private philanthropists have also demonstrated excitement in the field by investing in the use of brain interfacing technologies as a means to human augmentation. While the promise of incredible technologies is real, caution must be taken as implications regarding optimal performance and unforeseen side effects following device implantation into the brain are not fully characterized. The current study is aimed to quantify any motor deficit caused by microelectrode implantation in the motor cortex of healthy rats compared to non-implanted controls. Following electrode insertion, rats were tested on an open-field grid test to study gross motor function and a ladder test to study fine motor function. It was discovered that rats with chronically indwelling intracortical microelectrodes exhibited up to an incredible 527% increase in time to complete the fine motor task. This initial study defines the need for further and more robust behavioral testing of potential unintentional harm caused by microelectrode implantation.