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Despite changes in guideline-based management of moderate/severe traumatic brain injury (TBI) over the preceding decades, little impact on mortality and morbidity have been seen. This argues against the “one-treatment fits all” approach to such management strategies. With this, some preliminary advances in the area of personalized medicine in TBI care have displayed promising results. However, to continue transitioning toward individually-tailored care, we require integration of complex “-omics” data sets. The past few decades have seen dramatic increases in the volume of complex multi-modal data in moderate and severe TBI care. Such data includes serial high-fidelity multi-modal characterization of the cerebral physiome, serum/cerebrospinal fluid proteomics, admission genetic profiles, and serial advanced neuroimaging modalities. Integrating these complex and serially obtained data sets, with patient baseline demographics, treatment information and clinical outcomes over time, can be a daunting task for the treating clinician. Within this review, we highlight the current status of such multi-modal omics data sets in moderate/severe TBI, current limitations to the utilization of such data, and a potential path forward through employing integrative neuroinformatic approaches, which are applied in other neuropathologies. Such advances are positioned to facilitate the transition to precision prognostication and inform a top-down approach to the development of personalized therapeutics in moderate/severe TBI.

Adults exposed to blast and blunt impact often experience mild traumatic brain injury, affecting neural functions related to sensory, cognitive, and motor function. In this perspective article, we will review the effects of impact and blast exposure on functional performance that requires the integration of these sensory, cognitive, and motor control systems. We describe cognitive-motor integration and how it relates to successfully navigating skilled activities crucial for work, duty, sport, and even daily life. We review our research on the behavioral effects of traumatic impact and blast exposure on cognitive-motor integration in both younger and older adults, and the neural networks that are involved in these types of skills. Overall, we have observed impairments in rule-based skilled performance as a function of both physical impact and blast exposure. The extent of these impairments depended on the age at injury and the sex of the individual. It appears, however, that cognitive-motor integration deficits can be mitigated by the level of skill expertise of the affected individual, suggesting that such experience imparts resiliency in the brain networks that underly the control of complex visuomotor performance. Finally, we discuss the next steps needed to comprehensively understand the impact of trauma and blast exposure on functional movement control.

Major depressive disorder (MDD) is a prominent cause of disability worldwide. Current antidepressant drugs produce full remission in only about one-third of MDD patients and there are no biomarkers to guide physicians in selecting the best treatment for individuals. There is an urgency to learn more about the etiology of MDD and to identify new targets that will lead to improved therapy and hopefully aid in predicting and preventing MDD. There has been extensive interest in the roles of the immune system and the gut microbiome in MDD and in how these systems interact. Gut microbes can contribute to the nature of immune responses, and a chronic inflammatory state may lead to increased responsiveness to stress and to development of MDD. The gut microbiome-immune system-brain axis is bidirectional, is sensitive to stress and is important in development of stress-related disorders such as MDD. Communication between the gut and brain involves the enteric nervous system (ENS), the autonomic nervous system (ANS), neuroendocrine signaling systems and the immune system, and all of these can interact with the gut microbiota. Preclinical studies and preliminary clinical investigations have reported improved mood with administration of probiotics and prebiotics, but large, carefully controlled clinical trials are now necessary to evaluate their effectiveness in treating MDD. The roles that several gut microbe-derived molecules such as neurotransmitters, short chain fatty acids and tryptophan play in MDD are reviewed briefly. Challenges and potential future directions associated with studying this important axis as it relates to MDD are discussed.

Magnetic resonance imaging (MRI) is a non-destructive technique that is capable of localizing pathologies and assessing other anatomical features (e.g., tissue volume, microstructure, and white matter connectivity) in postmortem, ex vivo human brains. However, when brains are removed from the skull and cerebrospinal fluid (i.e., their normal in vivo magnetic environment), air bubbles and air–tissue interfaces typically cause magnetic susceptibility artifacts that severely degrade the quality of ex vivo MRI data. In this report, we describe a relatively simple and cost-effective experimental setup for acquiring artifact-free ex vivo brain images using a clinical MRI system with standard hardware. In particular, we outline the necessary steps, from collecting an ex vivo human brain to the MRI scanner setup, and have also described changing the formalin (as might be necessary in longitudinal postmortem studies). Finally, we share some representative ex vivo MRI images that have been acquired using the proposed setup in order to demonstrate the efficacy of this approach. We hope that this protocol will provide both clinicians and researchers with a straight-forward and cost-effective solution for acquiring ex vivo MRI data from whole postmortem human brains.

Tinnitus is the conscious perception of sound heard in the absence of physical sound sources external or internal to the body, reflected in aberrant neural synchrony of spontaneous or resting-state brain activity. Neural synchrony is generated by the nearly simultaneous firing of individual neurons, of the synchronization of membrane-potential changes in local neural groups as reflected in the local field potentials, resulting in the presence of oscillatory brain waves in the EEG. Noise-induced hearing loss, often resulting in tinnitus, causes a reorganization of the tonotopic map in auditory cortex and increased spontaneous firing rates and neural synchrony. Spontaneous brain rhythms rely on neural synchrony. Abnormal neural synchrony in tinnitus appears to be confined to specific frequency bands of brain rhythms. Increases in delta-band activity are generated by deafferented/deprived neuronal networks resulting from hearing loss. Coordinated reset (CR) stimulation was developed in order to specifically counteract such abnormal neuronal synchrony by desynchronization. The goal of acoustic CR neuromodulation is to desynchronize tinnitus-related abnormal delta-band oscillations. CR neuromodulation does not require permanent stimulus delivery in order to achieve long-lasting desynchronization or even a full-blown anti-kindling but may have cumulative effects, i.e., the effect of different CR epochs separated by pauses may accumulate. Unlike other approaches, acoustic CR neuromodulation does not intend to reduce tinnitus-related neuronal activity by employing lateral inhibition. The potential efficacy of acoustic CR modulation was shown in a clinical proof of concept trial, where effects achieved in 12 weeks of treatment delivered 4–6 h/day persisted through a preplanned 4-week therapy pause and showed sustained long-term effects after 10 months of therapy, leading to 75% responders.