We extend our high-resolution MRI-based Finite Element (FE) head model, previously presented and validated in [1–3], by considering the heterogeneities of the white matter structures captured through the use of Magnetic Resonance Elastography (MRE). This approach imparts more sophistication to our numerical model and yields results that more closely match experimental results. It is found that the peak pressure more closely matches the experiments as compared to the heterogeneous case. Qualitatively, we find differences in stress wave propagation near the corpus callosum and the corona radiata, which are stiffer on average than the global white matter. We are able to study the effects of these stiff structures on transient stress wave propagation within the cerebrum, something that cannot be done with a homogenized material model.

Tissues of the brain, especially white matter, are extremely heterogeneous - with constitutive response varying spatially. In this paper, we implement a high-resolution Finite Element (FE) head model where heterogeneities of white matter structures are introduced through Magnetic Resonance Elastography (MRE) experiments. Displacement of white matter under shear wave excitation is captured and the material properties determined though an inversion algorithm are directly used in the FE model. This approach is found to improve model predictions when compared to experimental results. In the first place, responses in the cerebrum near stiff structures such as the corpus callosum and corona radiata are markedly different compared with a homogenized material model. Additionally, the heterogeneities introduce additional attenuation of the shear wave due to wave scattering within the cerebrum.

Injuries from exposure to blasts are of significant concern in military operational settings, including tactical training, and is associated with self-reported concussion-like symptomology and physiological changes as increased intestinal permeability (IP) investigated herein. Timeseries gene expression and IP biomarker data were generated from “breachers” exposed to controlled, low-level explosive blast during training. Samples from 30 male participants at pre, post, follow-up blast exposure the next day were assayed via RNA-seq and ELISA. A battery of symptom data was also collected at each of these time points that acutely showed elevated symptom reporting related to headache, concentration, dizziness, and slowed thinking, dissipating ~16hrs following blast exposure. Evidence for bacterial translocation into circulation following blast exposure was detected by significant stepwise increase in microbial diversity (measured via alpha-diversity p=0.049). Alterations in levels of IP protein biomarkers (i.e., Zonulin, LBP, Claudin-3, I-FABP) assessed in a subset of these participants (n=23) further evidenced blast exposure associates with IP. The observed symptom profile was consistent with mTBI and was further associated with changes in bacterial translocation and intestinal permeability, suggesting that IP may be linked to a decrease in cognitive performance. These preliminary findings show for the first

People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely diagnose and assess complications long-term. Insufficient information is available regarding how to precisely diagnose and assess mTBI. This study identified and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated in this pilot study, including 11 mTBI cases (27.3% females; mean age of 28.7 years, SD=5.92) and 14 healthy controls (64.3% females; mean age of 22.0, SD=4.13). All the participants were assessed for cognitive (by NIH toolbox—executive function, memory, and processing speed), psychological (by PROMIS—depression, anxiety, and sleep disturbances), visual function (by King-Devick and binocular accommodative tests), postural balance performance (by a force plate), and blood 5-mC% (global methylation) levels. Students with mTBI reported significantly poorer episodic memory, severe anxiety, and more sleep disturbance problems. They also had higher blood 5-mC% level (all p’s<.05). No significant differences were found in visual function and postural balance. These findings validate changes in cognitive, psychosocial, and global DNA methylation long after mTBI.

This review explores the application of the conservative management model for pain to sports-related concussions (SRCs), framing concussions as a distinct form of pain syndrome with a pathophysiological foundation in central sensitization. Drawing parallels with proven pain management models, we underscore the significance of a proactive approach to concussion management. Recognizing concussions as a pain syndrome allows for the tailoring of interventions in alignment with conservative principles. This review first covers the epidemiology and controversies surrounding prolonged concussion recovery and persistent post-concussion symptoms (PPCS). Next, the pathophysiology of concussions is presented within the central sensitization framework, emphasizing the need for early intervention to mitigate the neuroplastic changes that lead to heightened pain sensitivity. Five components of the central sensitization process specific to concussion injuries are highlighted as targets for conservative interventions in the acute period: peripheral sensitization, cerebral metabolic dysfunction, neuroinflammation, glymphatic system dysfunction, and pain catastrophizing. These proactive interventions are emphasized as pivotal in accelerating concussion recovery and reducing the risk of prolonged symptoms and PPCS, in line with the philosophy of conservative management.