ARTICLE | doi:10.20944/preprints202308.0238.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: VMAT; stereotactic radiosurgery; brain tumor-related epilepsy; overall survival; brain metastasis; brain location
Online: 2 August 2023 (16:01:27 CEST)
Whole-brain radiation therapy and stereotactic radiosurgery are two treatment modalities commonly utilized to treat brain metastases (BMs). The aim of this study is to retrospectively analyze the main radio-oncologic and clinical-demographic aspects of a cohort of BM patients treated with Volumetric Modulated Arc Therapy for radiosurgery (VMAT-RS). This is a cross-sectional observational design study with retrospective review of medical records of patients with brain metastases treated with VMAT- RS between 2012 and 2018. Clinical and demographic data, with special attention to sex, age, primary tumor, brain tumor-related epilepsy (BTRE), number and brain location of BMs, Karnofsky Performance Status (KPS), the updated DS-GPA prognostic index and the survival estimated according to the Kaplan-Meier model from the date of radiosurgery were analyzed. One hundred and twenty-one patients with 229 BMs were treated with VMAT-RS. Patients presented 1-4 BMs, which were treated with 5 non-coplanar VMAT arcs. Sixty-eight percent of the patients had lung cancer and 35% of the BMs were in the frontal lobe. Proportion of local control was 88.5%. BTRE prevalence was 30.6%. The median survival time (MST) was 7.7 months. In the multivariate analysis of the Cox Regression model KPS70 (HRKPS<70=2.59; p=0.001) and higher DS-GPA (HRDS-GPAII =0.55, p=0.022; HRDS-GPAIII-IV =0.38, p=0.006) were associated with improved survival. In the univariate analysis, primary tumor, age and the presence of metastases in the posterior fossa (PFBMs) were also significative. In conclusion, the VMAT-RS is a technique with an overall survival comparable to other radiosurgery techniques. The median survival is significantly longer in those with higher KPS and DS-GPA. Other variables such as the type of primary tumor, age and PFBMs could also influence survival, although further studies are needed.
REVIEW | doi:10.20944/preprints202311.0929.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Secondary TBI; Traumatic Brain Injury; Brain Injuries; Physiopathology
Online: 14 November 2023 (12:58:03 CET)
Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality among all ages; despite the advances, understanding pathophysiological responses after TBI is still complex, involving multiple mechanisms. Previous reviews have focused on potential targets; however, the research on potential targets has continuously grown in the last five years, bringing even more alternatives and elucidating previous mechanisms. Knowing the key and updated pathophysiology concepts is vital for adequate management and better outcomes. This article reviews the underlying molecular mechanisms, the latest updates, and future directions for pathophysiology-based TBI management.
REVIEW | doi:10.20944/preprints202303.0237.v1
Subject: Engineering, Bioengineering Keywords: microelectrodes; brain implants; brain-computer interface; DBS; ECoG
Online: 13 March 2023 (15:37:35 CET)
Intracortical microelectrodes that can be implanted have the ability to capture fast-changing neuron action potentials in the living brain. Despite this potential, many obstacles must still be overcome for reliable, long-term, high-quality recordings and accurate analysis of brain activity. These challenges include improving recording quality, enhancing recording stability, increasing recording capacity, and adding multi-functional features. One potential approach to enhance implantable microelectrodes involves the advancement of materials, refinement of implantation methodologies, and augmentation of the number of sites for recording. However, these challenges are still being actively researched, and advancements in microelectrode technology are underway. The difficulties with implantable microelectrodes are evaluated, and solutions are presented from different perspectives. The latest advancements in microelectrode technology are reviewed and condensed, and future possibilities are explored.
REVIEW | doi:10.20944/preprints202004.0028.v1
Online: 3 April 2020 (08:14:18 CEST)
Along just over a century of research we moved from learning how to cultivate tissues in a dish to grasping the concepts for creating an entire brain in a vat. As we approach the divisive moment in which we can first detect signs of awareness in such artificially developed organoids, we need to lay foundation for what lays ahead. It is crucial that ethical, legal and moral implications of organoid research are clear and that boundaries are set to separate scientific progress from human life preservation. The largest obstacle may be the definition of consciousness itself, which has arguably been historically neglected by philosophy, psychology and neurosciences at large. One reason may be the difficulties posed by the underlying qualities of awareness, such as its subjective and heterogeneous nature. Another reason may lie on the possibly that consciousness is an overarching emergent property of our brain. For the time being, one can see brain organoids as philosophical zombies, physical analogues of the human brain which mimic sentient human reactions but lack experiential properties of sensation (a.k.a. qualia).
REVIEW | doi:10.20944/preprints202211.0447.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: EEG; stroke; traumatic brain injury; neurorehabilitation; brain-machine interface
Online: 24 November 2022 (02:08:43 CET)
Background: There is an increasing interest in the role of EEG in neurorehabilitation. We primarily aimed to identify the knowledge base through highly influential studies. Our secondary aims were to imprint the relevant thematic hotspots, research trends, and social networks within the scientific community. Methods: We performed an electronic search in Scopus looking for studies reporting on rehabilitation in patients with neurological disabilities. The most influential papers outlined the knowledge base, while a word co-occurrence analysis imprinted the research hotspots. Likewise, co-citation analyses highlighted collaboration networks between Universities, authors, and countries. The results were presented in summary tables, burst detection plots, and geospatial maps. Finally, a content review based on the top-20 most cited articles completed our study. Results: Our current bibliometric study was based on 874 records from 420 sources. There was a vivid research interest in EEG use for neurorehabilitation, with an annual growth rate as high as 14.3%. The most influential paper was the study titled "Brain-computer interfaces, a review" by Nicolas-Alfonso LF and Gomez-Gill J, with 997 citations, followed by "Brain-computer interfaces in neurological rehabilitation" by Daly J. and Wolpaw JR (708 citations). The USA, Italy, and Germany were among the most productive countries. The research hotspots shifted with time from the use of “functional magnetic imaging” to EEG-based “brain-machine interface”, “motor imagery”, and “deep learning”. Conclusions: EEG constitutes the most significant input in brain-computer interfaces (BCI) and can be successfully used in the neurorehabilitation of patients with stroke, amyotrophic lateral sclerosis, and traumatic brain and spinal injury. EEG-based BCI facilitates training, communication, and control of wheelchair and exoskeletons. However, research is limited to specific scientific groups from developed countries. Evidence is expected to change with the broader availability of BCI and improvement in EEG filtering algorithms.
REVIEW | doi:10.20944/preprints202202.0050.v1
Subject: Engineering, Bioengineering Keywords: Neuroprosthetics; Brain Computer Interface; Neural Implants; Deep Brain Stimulation
Online: 3 February 2022 (11:06:15 CET)
Recent progress in microfabrication technique allowed the rapid development of neural implants. They are getting categorized as effective tools for clinical practice, especially to treat traumatic and neurodegenerative disorders. Microelectrode arrays already have been used in numerous neural interface devices. Basically, almost all neural implants have been developed based on BCI (Brain Computer Interface) system. When BCI system falls under invasive technique, it is referred as BMI or Brain Machine Interface. BMIs hold promises for neurorehabilitation of motor and sensory function, cognitive state evaluation and treatment of neurological chaos. A directed overview of the field of neural implants is discussed in this article. The aim of this review is to give a brief introduction of neural prosthetics as well as their exciting applications in treating neurological disorders and a deep discussion on their functionality are mentioned. BCI system and their different types, their functionality, their pros and cons, how other neural implants developed, and their present status have been covered. Different possibilities and possible future of deep brain stimulation (DBS), Neuralink, motor and sensory neural prosthetics are further discussed.
ARTICLE | doi:10.20944/preprints202007.0366.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: mTBI; MRI; MRE; brain wave dynamics; FE brain model
Online: 17 July 2020 (06:21:09 CEST)
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.
ARTICLE | doi:10.20944/preprints202006.0212.v1
Subject: Physical Sciences, Condensed Matter Physics Keywords: neural synchronization; consciousness; quantum biology; brain dynamics; brain connectivity
Online: 17 June 2020 (09:29:28 CEST)
One of the biggest queries in cognitive sciences is the emergence of consciousness from matter. Modern neurobiological theories of consciousness propose that conscious experience is the result of interactions between large-scale neuronal networks in the brain, traditionally described within the realm of classical physics. Here, we propose a generalized connectionist framework in which the emergence of “conscious networks” is not exclusive of large brain areas, but can be identified in sub-cellular networks exhibiting non-trivial quantum phenomena. The essential feature of such networks is the existence of strong correlations in the system (classical or quantum coherence) and the presence of an optimal point at which the system’s complexity is maximized, expressed either by maximization of the information content in large scale functional networks or by achieving optimal efficiency through the quantum Goldilock effect.
REVIEW | doi:10.20944/preprints202110.0071.v1
Online: 5 October 2021 (08:46:35 CEST)
A brain tumor is an abnormal mass of tissue found inside the brain that consists of cells that grow and multiply without any control and unchecked by the mechanisms that regulate normal cell growth. It is one of the leading causes of death in many different regions worldwide, affecting various ages, sex, race, or ethnicities. Besides being a life-threatening condition, it can also disrupt normal brain function leading to severe cognitive morbidity. Additionally, the cost associated with active treatment and palliative care of the brain tumor most often proves to be out of reach for many people. Over the past decades, even though we have several published literature showing the epidemiology and characteristics of brain tumors, up-to-date epidemiological data is yet to be published. This review will provide comparable recent statistics regarding the incidence of brain tumors in 3 different regions; - the USA, the UK, and Australia. Also, a focus will be given to brain tumor’s key characteristics, classifications, and treatment protocol.
ARTICLE | doi:10.20944/preprints202309.1491.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Blood-brain barrier; Brain ischaemia; Stroke; Biomarker; Tight Junction protein
Online: 21 September 2023 (12:16:03 CEST)
The blood-brain barrier (BBB) acts as a specialized structure separating the brain from peripheral blood circulation and plays an important role in brain function. Following an ischaemic stroke or cerebral ischaemia, the BBB is damaged leading to degraded proteins being released into blood circulation. However, little is known about cerebral ischaemia and reperfusion (I/R) induced BBB damage and changes in circulatory biomarkers. This study aims to use both immunohistochemistry and western blotting (WB) to examine neuronal death, glial cell alterations and changes in BBB tight junction (TJ) proteins such as zonula occludens-1 (ZO-1), Occludin and Claudin-5 in the hippocampus in a murine model of cerebral I/R. The changes in these proteins in the blood serum of this model were assessed by enzyme-linked immunosorbent assay. The results showed neuronal death and a significant increase in glial fibrillary acidic protein (GFAP), a protein primarily expressed in astrocytes and a significant decrease in TJ proteins, ZO-1, Occludin and Claudin-5 in the hippocampus of occluded mice as compared to sham-operated mice. These changes are associated with an increased level of these proteins in blood serum in ischaemic mice, suggesting that these proteins can be used as potential biomarkers for determining ischaemic stroke.
ARTICLE | doi:10.20944/preprints202211.0530.v1
Subject: Computer Science And Mathematics, Applied Mathematics Keywords: Brain Diseases; Blood-Brain Barrier; Magnetic Field; Nanoparticle; Drug Delivery
Online: 29 November 2022 (03:34:14 CET)
Magnetic Nanoparticles (MNPs) is a promising technique to cure brain diseases. On the one hand, by serving as drug carriers, they can bypass the blood-brain barrier and deliver drug molecules to the brain parenchyma; on the other hand, their transport trajectory can be manipulated by applying an external magnetic field. However, due to the complex microstructure of brain tissues, e.g. the anisotropy of white matter (WM), how to achieve desired drug distribution patterns, e.g. uniform distribution, by tuning the drug delivery system is largely unknown. Here, in this study, by adopting a mathematical model capable of capturing the diffusion trajectories of MNPs in the microstructures, we systematically investigated the effects of key parameters in the MNPs delivery system on the equivalent diffusion coefficient of MNPs in the microenvironment of brain WM. The results show that uniform distribution of MNPs in anisotropic tissues can be achieved by adjusting the particle size and magnetic field. We have not only obtained a deeper understanding on how to optimise the MNPs delivery system, it can also be anticipated that an improved mathematical model could even help to achieve complex drug distribution patterns in the complicated brain environment by designing an appropriate combination of the key parameters.
REVIEW | doi:10.20944/preprints202012.0415.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: nutrition; brain; neurodevelopment; childhood; gut-brain axis; psychobiotics; macronutrients, micronutrients.
Online: 16 December 2020 (13:52:17 CET)
Proper nutrition is crucial for normal brain and neurocognitive development. Failure to optimize neurodevelopment early in life can have profound long-term implications for both mental health and quality of life. Although the first 1000 days of life represent the most critical period of neurodevelopment, the central and peripheral nervous systems continue to develop and change throughout life. All this time, development and functioning depend on many factors, including adequate nutrition. In this review, we outline the role of nutrients in cognitive, emotional, and neural development in infants and young children with special attention to the emerging roles of polar lipids and high quality (available) protein. Furthermore, we discuss the dynamic nature of the gut-brain axis and the importance of microbial diversity in relation to a variety of outcomes, including brain maturation/function and behavior are discussed. Finally, the promising therapeutic potential of psychobiotics to modify gut microbial ecology in order to improve mental well-being is presented. Here we show that the individual contribution of nutrients, their interaction with other micro-and macronutrients, and the way in which they are organized in the food matrix are of crucial importance for normal neurocognitive development.
REVIEW | doi:10.20944/preprints201912.0096.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: brain connectivity; brain development; gut-brain axis; neurodevelopmental diseases; neuronal cytoarchitecture; neuroplasticity; regulatory T cells; serotonin (5-HT)
Online: 7 December 2019 (16:55:39 CET)
Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows to rescue long term potentiation (LTP) and long term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, possibly playing a role in the gut-brain axis, and modulates the function of immune cells. In this review, we will mainly focus on recent findings on this receptor’s role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gut and immune system.
ARTICLE | doi:10.20944/preprints202306.0623.v1
Subject: Engineering, Bioengineering Keywords: Epilepsy; Electroencephalogram; Convolutional neural networks; Brain signal integral; Brain signal derivative
Online: 8 June 2023 (10:13:28 CEST)
Epilepsy is a neurological disorder that affects approximately 1% of the world's population. To diagnose and estimate the occurrence of epilepsy, the analysis of recorded brain activity is performed by a neurologist, which is not only time-consuming and tedious but also occasionally accompanied by human error. Therefore, in recent decades, researchers have aimed to unravel an approach for designing and building an automated method for diagnosing and estimating the occurrence of epilepsy. Accordingly, the present study proposed two new-fangled ways based on brain signals and a convolutional neural network (CNN). Moreover, this research implements a CNN with a sequential three-layer structure. Numerous experiments were performed, and the accuracy of estimating epilepsy using the developed methods was achieved at 95% without feedback and 97% with feedback. The proposed methods were proven to be more accurate than the previous techniques and can be employed as a physician's assistant once entering the field of operation.
ARTICLE | doi:10.20944/preprints202105.0099.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: COVID-19-sleep disorders; brain mechanisms; the blood-brain barrier permeability.
Online: 6 May 2021 (15:09:41 CEST)
Here, we review findings and trends in sleep research in 2020-2021 demonstrating how COVID-19 and sleep disorders can induce the BBB leakage via neuroinflammation, which might contribute to the 'coronasomnia' phenomenon. The new studies suggest that the controlling of sleep hygiene and quality should be incorporated into the rehabilitation of COVID-19 patients. We also discuss perspective strategies for prevention of COVID-19-related BBB disorders. We demonstrate that sleep might be a novel biomarker of the BBB leakage and the analysis of sleep EEG patterns can be a breakthrough non-invasive technology for diagnosis of the COVID-19-caused BBB disruption.
REVIEW | doi:10.20944/preprints201811.0171.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Autism, ASD, microbiota, gut-brain-axis, microbiota-gut-brain-axis, therapy
Online: 7 November 2018 (14:45:10 CET)
New research points to a possible link between Autism Spectrum Disorder and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites or leaky gut in autistic people are described. Various altered metabolite levels were observed in autistic children, many of those were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides. A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients triggering new body responses or altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in the cells, altered tight junctions in the blood brain barrier and structural changes in cortex, hippocampus, amygdala and cerebellum were detected. Moreover, this paper suggests that autism is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between autism and gut microbiota is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health. Diagnostic and therapeutic value of new biomarkers leading to the perturbation in the phenylalanine metabolism will be discussed.
REVIEW | doi:10.20944/preprints201609.0077.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: glutamate; glutamine; BBB (blood brain-barrier); brain; oxoproline; amino acid transport
Online: 23 September 2016 (03:23:29 CEST)
A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.
CASE REPORT | doi:10.20944/preprints202303.0402.v1
Online: 22 March 2023 (14:50:00 CET)
Introduction: Adverse events related to vaccines are reactions that can lead to serious complications, in the present that we live at the publication of this article with the need to generate high rates of vaccination have been presented in the case of vaccine agents against COVID-19 adverse events, with thrombotic events being the most important. Case Presentation: This is a 37-year-old female patient who presents 11 days after ChAdOx1-S vaccination against COVID-19 presents with intense headache associated with symptoms of intracranial hypertension, she was initially taken to simple cranial tomography showing presence of cerebral edema and indirect signs of cerebral venous thrombosis, it is proposed to carry out cerebral angiography which showed the presence of thrombosis of both transverse venous sinuses, no hypercoagulability states were found in the laboratories, the immunological tests carried out for antiphospholipid syndrome were negative, the thrombotic event was associated with the ChAdOx1-S vaccine, later the patient was taken to thrombectomy by Neuroradiology, achieving complete channeling of both transverse venous sinuses. Conclusions: Adverse events associated with vaccination have been described with multiple vaccine agents, this component against COVID-19 is also an event to consider, knowing the pathophysiology of these events is essential to be able to reduce these risks and select the least risky agent. Despite this risk, vaccination remains the only cost-effective measure to reduce the morbidity and mortality associated with COVID-19.
REVIEW | doi:10.20944/preprints202302.0452.v2
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Neurocognition; MRI; Intelligence; Brain
Online: 3 March 2023 (02:44:38 CET)
Brain magnetic resonance imaging (MRI) offers a unique lens to study neuroanatomic support of human neurocognition and intelligence. A core mystery is the MRI explanation of individual differences in neurocognition and intelligence. The past four decades have seen great advancement in studying this century-long mystery, but the sample size and population-level studies limit the explanation at the individual level. The recent rise of big data and artificial intelligence offers novel opportunities. Yet, data sources, harmonization, study design, and interpretation need to be carefully considered. This review aims to summarize past work, discuss rising opportunities and challenges, and facilitate further investigations on machine intelligence inferring human intelligence.
ARTICLE | doi:10.20944/preprints202302.0195.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Traumatic brain injury; hippocampus
Online: 13 February 2023 (02:24:00 CET)
Background: Traumatic brain injury (TBI) remains a significant risk factor for post-traumatic epilepsy (PTE). The pathophysiological mechanisms underlying the injury-induced epileptogenesis are under under investigation. The dentate gyrus, a structure highly susceptible to injury, and has been implicated in the evolution of seizure development. Methods: Utilizing the murine unilateral focal control cortical impact (CCI) injury, we evaluated seizure onset using 24/7 EEG video analysis at 2-4 months post-injury. Cellular changes in the dentate gyrus and hilus of the hippocampus were quantified by non-biased stereology and Imaris image analysis to evaluate Prox1-positive cell migration, astrocyte branching and morphology, as well as neuronal loss at four months post-injury. Isolation of region-specific astrocytes and RNA-seq was performed to determine differential gene expression in PTE+ vs. PTE- that may comport with the epileptogenic process. Results: CCI injury resulted in 37% PTE+-incidence, which increased with injury severity and hippocampal damage. Histological assessments uncovered a significant loss of hilar interneurons that coincided with aberrant migration of Prox1-positive granule cells and reduced astroglial branching in PTE+ compared to PTE- mice. We uniquely identified Cst3 as a PTE+-specific gene signature in astrocytes across all brain regions. Conclusions: These findings suggest that epileptogenesis may emerge following TBI due to distinct aberrant cellular remodeling events and key molecular changes in the dentate gyrus of the hippocampus.
ARTICLE | doi:10.20944/preprints201811.0588.v1
Subject: Physical Sciences, Astronomy And Astrophysics Keywords: Artificial Intelligence, Brain Simulation
Online: 26 November 2018 (11:34:04 CET)
We introduce a mission design for an interstellar expedition to nearby earth-like exoplanets, which our analysis determined to be Tau Ceti and Gliese 667C, at the time of analysis in 2013. We review the research problems in propulsion and AGI that must be addressed to launch an AI guided interstellar probe within 100 years. We propose a new semi-autonomous agent approach for intelligent control of the spacecraft. We introduce the concept of a semi-autonomous agent as having built-in safety guarantees that constrain operation. An autonomous agent case study is presented formulating the objective, constraints, AGI implementation of the agent based on Solomono's Alpha architecture, and adding specicity. We discuss the training required to reach human-level and trans-sapient levels of intelligence which corresponds to an entire crew of AI experts specialized in elds such as astrophysics, astromechanics, astrobiology, quantum physics, computer science, molecular biology, and so forth. We project the feasibility of the human-level AI technology based on empirical ndings in neuroscience, and nd that it should be feasible by 2030. We analyze Solomono's innity point hypothesis in light of Koomey's law about energy eciency of computing and nd that the trends in 2013 indicated an early singularity by 2035, which implies that we might encounter physical bottlenecks which will decelerate computing technology improvements signicantly. We recommend thus year 2040 for launching the probe by which date other required technologies will have been developed. We discuss the scenario of a virtual crew made of brain simulations, which is a bio-information based AI approach. We detail the subsystems of command and control, communication, scientic instrumentation, power, propulsion, navigation, and shielding. We propose a variation of ICAN-II/AIMStar propulsion which uses a positron source instead of anti-protons to initiate micro-fusion reactions. We combine the positron initiated fusion pulse propulsion scheme with a miniaturized version of the Daedelus fusion thruster obtaining high performance. We derive two mission proles one for fusion pulse propulsion, and the yet hypothetical Q-Thruster. Fusion thruster requires 132.2 years for Tau Ceti, and 233.2 years for Gliese 667C, while Q-Thruster takes only 42.3 years for Tau Ceti, and 62.5 years for Gliese 667C. We also discuss extended roles for intelligent interstellar probes such as self-reproduction via nanotechnology, refueling, construction, robotic bodies, and transmission of brain simulations.
ARTICLE | doi:10.20944/preprints201811.0284.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: brain; spaceflight; microgravity; proteomics
Online: 12 November 2018 (10:51:57 CET)
There is evidence that spaceflight poses acute and late risks on the central nervous system. To explore possible mechanisms, the proteomic changes following spaceflight in mouse brain were characterized. Space Shuttle Atlantis (STS-135) was launched at the Kennedy Space Center on a 13-day mission. Within 3–5 hours after landing, brain tissue was collected to evaluate protein expression profiles using quantitative proteomic analysis. Our results showed that there were 26 proteins that were significantly altered after spaceflight in the grey and/or white matter. While there was no overlap between the white and grey matter in terms of individual proteins, there was overlap in terms of function, synaptic plasticity, vesical activity, protein/organelle transport, and metabolism. Our data demonstrate that exposure to the spaceflight environment induces significant changes in protein expression related to neuronal structure and metabolic function. This might lead to a significant impact on brain structural and functional integrity that could affect the outcome of space missions.
REVIEW | doi:10.20944/preprints202310.0557.v1
Subject: Biology And Life Sciences, Other Keywords: nerve regeneration; non-coding RNAs; exosome; traumatic brain injury; blood-brain barrier
Online: 10 October 2023 (03:25:35 CEST)
Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.
REVIEW | doi:10.20944/preprints202306.1636.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: clinical decision support system; brain tumour; brain neoplasms; diagnosis; prognosis; systematic review
Online: 22 June 2023 (14:59:46 CEST)
The abnormal accumulation of cells in the human brain, if left untreated, may cause brain damage. Management and treatment of these tumours require an early and accurate diagnosis, while their prognostic characterisation can also be beneficial in the choice of care planning for the patient. CDSSs are being continuously developed and integrated into routine clinical practice as they assist clinicians and radiologists to deal with an enormous amount of medical data, reduce clinical errors, and improve diagnostic capabilities. They assist detection, classification, and grading of brain tumours as well as alerting physicians of requirement of change in treatment plans. The aim of this systematic review is to identify various CDSSs used in brain tumour diagnosis and prognosis, that rely on data captured by any imaging modality. Based on the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, the literature search was conducted in PubMed and Engineering Village Compendex databases. This review examines various CDSS tool types, system features, techniques used, accuracy, and outcome, to provide the latest evidence available in the field of neuro-oncology. An overview of different types of CDSSs used to support clinical decision-making in the management and treatment of brain tumours, along with highlighting their benefits, challenges, and future perspectives has been provided.
ARTICLE | doi:10.20944/preprints202305.1994.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: brain; metastasis; breast cancer; interferon-; blood-brain barrier; immune response; T lymphocytes
Online: 29 May 2023 (08:24:41 CEST)
The appearance of brain metastasis is the most serious complication of breast cancer with mostly fatal outcomes. To reach the brain, tumor cells need to pass the blood-brain barrier (BBB). The molecular mechanisms underlying penetration of the BBB are largely unknown. Previously we found that tumor-infiltrating T lymphocytes enhance the development of brain metastasis of estrogen receptor-negative (ER-) breast cancer. In the current study, we investigate the contribution of T lymphocytes and the IFN- pathway in enabling breast cancer cells to pass the in vitro BBB. CD8+ cells display the strongest stimulatory effect on breast cancer cell passage. We show that inhibition of the IFN- receptor in MDA-MB-231 breast cancer cells, or neutralization of soluble IFN-, impairs the in vitro trespassing of breast cancer cells. Importantly, we validated our findings using gene expression data of breast cancer patients. CXCL-9,-10,-11/CXCR3 axis, dependent on IFN- signaling activity, was overexpressed in primary breast cancer samples of patients who developed brain metastasis. The data support a role for T-lymphocytes and the IFN- pathway in the formation of brain metastasis of ER- breast cancer, and offer targets to design future therapies for preventing breast cancer cells to cross the BBB.
REVIEW | doi:10.20944/preprints202212.0207.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Blood-Brain Barrier; Brain Drug Delivery; Carbon Nanomaterials; Cerebral Gliomas; Glioblastoma; Nanoparticles.
Online: 12 December 2022 (14:56:45 CET)
Malignant gliomas are the most common primary brain tumors in adults up to an extent of 78% of all primary malignant brain tumors. However, total surgical resection is almost unachievable due to considerable infiltrative ability of glial cells. The efficacy of current multimodal therapeutic strategies is, furthermore, limited by the lack of specific therapies against malignant cells, and, therefore, the prognosis these in patients is still very unfavorable. The limitation of conventional therapies, which may result from inefficient delivery of the therapeutic or contrast agent to brain tumors are major reasons for this unsolved clinical problem. The major problem in brain drug delivery is the presence of the blood brain barrier which limits the delivery of many chemotherapeutic agents. Nanoparticles, thanks to their chemical configuration, are able to go through the blood-brain barrier carrying drugs or genes targeted against gliomas. Carbon nanomaterials show distinct properties including electronic properties, penetrating capability on the cell membrane, high drug-loading and pH-dependent therapeutic unloading capacities, thermal properties, large surface area and easy modification with molecules, which render them as a suitable candidate to deliver drugs. In this review we will focus on the potential effectiveness of the use of carbon nanomaterials in the treatment of malignant gliomas discussing the current progress of in vitro and in vivo researches of carbon nanomaterials-based drug delivery to brain.
REVIEW | doi:10.20944/preprints202103.0770.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: CDP-choline; citicoline; pharmacological neuroprotection; brain ischemia; traumatic brain injury; head injury
Online: 31 March 2021 (14:42:27 CEST)
Head injury is among the most devastating types of injury, specifically called Traumatic Brain Injury (TBI). There is need to diminish the morbidity related with TBI and to improve the outcome of patients suffering TBI. Among the improvements on the treatment of TBI, neuroprotection is one of the upcoming improvements. Citicoline has been used in the management of brain ischemia related disorders, such as TBI. Citicoline has biochemical, pharmacological, and pharmacokinetic characteristics that make it a potentially useful neuroprotective drug for the management of TBI. A short review of these characteristics is included in this paper. Also, a narrative review of almost all the published or communicated studies performed with this drug in the management of patients with head injury is included. Based on the results obtained in these clinical studies, it is possible to conclude that citicoline was able to accelerate recovery of consciousness and to improve the outcome of this kind of patients, with an excellent safety profile. Thus, citicoline could have a potential role in the management of TBI.
REVIEW | doi:10.20944/preprints202103.0401.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: insulin; insulin receptor; brain insulin resistance; mitochondria; brain; neuron; H2O2; glutamate excitotoxicity.
Online: 15 March 2021 (17:38:24 CET)
Current hypotheses implicate insulin resistance of the brain as a pathogenic factor in the development of Alzheimer’s disease and other dementias, Parkinson’s disease, type 2 diabetes, obesity, major depression, and traumatic brain injury. A variety of genetic, developmental, and metabolic abnormalities that lead to disturbances in the insulin receptor signal transduction may underlie insulin resistance. Insulin receptor substrate proteins are generally considered to be the node in the insulin signaling system that is critically involved in the development of insulin insensitivity during metabolic stress, hyperinsulinemia, and inflammation. Emerging evidence suggests that lower activation of the insulin receptor (IR) is another common, while less discussed, mechanism of insulin resistance in the brain. This review aims to discuss causes behind the diminished activation of IR in neurons, with a focus on the functional relationship between mitochondria and IR during early insulin signaling and the related roles of oxidative stress, mitochondrial hypometabolism, and glutamate excitotoxicity in the development of IR insensitivity to insulin.
REVIEW | doi:10.20944/preprints202103.0372.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: insulin; insulin receptor; brain insulin resistance; mitochondria; brain; neuron; H2O2; glutamate excitotoxicity.
Online: 15 March 2021 (11:46:08 CET)
Current hypotheses implicate insulin resistance of the brain as a pathogenic factor in the development of Alzheimer’s disease and other dementias, Parkinson’s disease, type 2 diabetes, obesity, major depression, and traumatic brain injury. A variety of genetic, developmental, and metabolic abnormalities that lead to disturbances in the insulin receptor signal transduction may underlie insulin resistance. Insulin receptor substrate proteins are generally considered to be the node in the insulin signaling system that is critically involved in the development of insulin insensitivity during metabolic stress, hyperinsulinemia, and inflammation. Emerging evidence suggests that lower activation of the insulin receptor (IR) is another common, while less discussed, mechanism of insulin resistance in the brain. This review aims to discuss causes behind the diminished activation of IR in neurons, with a focus on the functional relationship between mitochondria and IR during early insulin signaling and the related roles of oxidative stress, mitochondrial hypometabolism, and glutamate excitotoxicity in the development of IR insensitivity to insulin.
REVIEW | doi:10.20944/preprints201807.0455.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: stereotactic radiosurgery (SRS); stereotactic radiotherapy (SRT); brain metastasis; immunotherapy; whole brain radiotherapy (WBRT)
Online: 24 July 2018 (11:47:15 CEST)
Stereotactic radiosurgery (SRS) has become increasingly important in the management of brain metastases due to improving systemic disease control and rising incidence. Initial trials demonstrated SRS with whole brain radiotherapy (WBRT) improved local control rates versus WBRT alone. Concerns with WBRT associated neurocognitive toxicity have contributed to greater use of SRS alone, including for patients with multiple metastases and following surgical resection. Molecular information, targeted agents and immunotherapy have also altered the landscape for the management of brain metastases. This review summarises current and emerging data on the role of SRS in the management of brain metastases.
COMMUNICATION | doi:10.20944/preprints202309.1053.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Oligodendroglioma; iron; pediatric; brain tumors
Online: 15 September 2023 (09:40:22 CEST)
Oligodendroglioma (OG) is a brain tumor that contributes to < 1% of brain tumor diagnoses in the pediatric population. Unfortunately, pediatric OG remains without definitive molecular characteristics to aid in diagnosis, and little is known about the tumor microenvironment. Tumor cells' metabolism and proliferation rate are generally higher than healthy cells, so their iron demand is also significantly increased. This consideration underlines the great importance of iron for tumor development and progression. In this context, this study aims to evaluate the effect of iron in a cellular in vitro model of human oligodendroglioma brain tumor. Cell morphology, the effect of siderotic medium on cell growth, iron uptake, and the expression of iron metabolism-related genes were evaluated by optic microscopy, ICP-MS, confocal microscopy, and RealTime PCR, respectively. This study underlines the great importance of iron for tumor development and progression, but also the possibility of reducing the available iron concentration to determine an antiproliferative effect on OGs. Therefore, every attempt can be promising to defeat the OGs for which there are currently no long-term curative therapies.
ARTICLE | doi:10.20944/preprints202305.1406.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Brain capillary endothelial cell(s)
Online: 19 May 2023 (08:15:17 CEST)
Brain capillary endothelial cell(s) (BECs) have numerous functions including their semipermeable interface-barrier (transfer and diffusion of solutes), trophic (metabolic homeostasis), tonic (vascular hemodynamics), and trafficking (vascular permeability, coagulation, and leukocyte extravasation) functions to provide brain homeostasis. BECs also serve as the brain’s sentinel cell of the innate immune system and are capable of antigen presentation. In metabolic syndrome (MetS) there are two regions resulting in proinflammatory signaling of BECs. Namely, visceral adipose tissue depots supplying excessive peripheral cytokines/chemokines (pCC) and gut microbiota dysbiotic regions supplying excessive soluble lipopolysaccharide (sLPS), small LPS-enriched extracellular vesicle exosomes (lpsEVexos), and pCC. This dual signaling of BECs at their receptor sites results in BEC activation and dysfunction (BECact/dys) and neuroinflammation. sLPS and lpsEVexos signal BECs toll-like receptor four, which then signals translocated nuclear factor kappa B (NFkB). Translocated NFkB promotes the synthesis and secretion of BEC proinflammatory cytokines and chemokines. Specifically, the chemokine CCL5 (RANTES) is capable of attracting microglia cells to BECs. BEC neuroinflammation activates perivascular space(s) (PVS) resident macrophages. Excessive phagocytosis by reactive resident PVS macrophages results in a stagnation-like obstruction, which along with increased capillary permeability due to BECact/dys could expand the fluid volume within the PVS to result in enlarged PVS (EPVS). Importantly, this remodeling may result in pre- and post-capillary EPVS that would contribute to their identification on T2-weighted MRI, which are considered to be biomarkers for cerebral small vessel disease.
REVIEW | doi:10.20944/preprints202203.0301.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Heart Failure; Gravity; Ischemia; Brain
Online: 22 March 2022 (12:38:29 CET)
During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.
REVIEW | doi:10.20944/preprints202111.0531.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: brain tumors; glioblastoma; angiogenesis; metformin
Online: 29 November 2021 (12:30:08 CET)
Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including GBM. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of the inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss the potential metformin’s antitumoral effects on GBM, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of GBM patients.
CONCEPT PAPER | doi:10.20944/preprints202104.0185.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: vasculature; connectomics; pathoconnectomics; connectivity; brain
Online: 6 April 2021 (18:32:55 CEST)
In recent years, pathoconnectomics emerged as an interesting framework for the investigation and better comprehension of disorders affecting the brain. Research in this field has used so far structural, functional, metabolic and genetic data, but limited attention was addressed to the possible role of vascularization. In the present work the following aspects making it a valuable candidate to pathoconnectomics investigation are discussed: i) The vascular system is by its nature a network, endowed with directionality information on the basis of circulation; ii) The current imaging techniques allow in vivo detection of the vascular system to a good level of detail; iii) The information extracted from this kind of data could interact in a meaningful way with the functional profile of the brain, being the BOLD effect in turn based on blood flow; iv) Further evidence could be found in support of the trophic failure hypothesis; v) Data about vascularization could allow to bring in the pathoconnectomics framework cardiovascular and metabolic disorders. We suggest, therefore, that the evaluation of vascular connectivity (which we propose to name “vesselomics”) could enhance the pathoconnectomics paradigm, and provide new elements towards the understanding of brain pathology.
ARTICLE | doi:10.20944/preprints201812.0365.v1
Online: 31 December 2018 (10:17:25 CET)
Since matter, energy and information are the three major components of the world, is there an interaction between information and matter? In the present work, the coevolution of human language and brain is taken as a case of interaction between information and brain. Some evidence that may show interactions between human language and brain revealed by previous researches is summarized in this paper, such as the language areas in the cerebral cortex of the modern human brain, the evolution of human language and brain in human history, and the genetic basis for the evolution of language. Based on the evidence, a dynamic model is developed to investigate the possible mechanism of coevolution of human language and brain. In the model, human language development and brain development reinforce each other: the developmental level of language can be promoted by advances in brain function due to language-related gene mutations, in turn, whether such mutations are selected positively can be influenced by the current developmental level of language. The coevolution of human language and brain can be taken as a case of interaction between information and matter.
ARTICLE | doi:10.20944/preprints201812.0017.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: primary brain tumor; HER2; immunohistochemistry
Online: 3 December 2018 (09:24:06 CET)
Background and objectives: Primary brain tumors include any tumors arising in the brain whose prognosis is poor due to their histologic characteristics. The aim of this research was to evaluate the frequency of HER2 tumor marker in primary malignant brain tumors. Materials and Methods: This descriptive study was conducted on the samples admitted to the pathology laboratory with diagnosis of primary brain tumor during 2008–2015. Results: From among 107 patients (61.7% males and the rest females) with mean age of 40.4 years, the highest frequency of tumor location was in supratentorial region of the brain (including lobes and ventricles) (63.85% cases). High-grade astrocytoma had the highest prevalence at diagnosis (43.9%), followed by low-grade astrocytoma (37.4%). As for HER2 score, 42.1% of patients were HER2-positive (scores 2 & 3). On the other hand, 5.6% of patients were HER2-negative (-), 40.2% were positive (+), and 54.2% were positive (++). The patients with high-grade astrocytoma had older age (P < 0.001), higher HER2 positivity (P = 0.024) and percentage (P < 0.001) compared to the patients with low-grade astrocytoma. Conclusions: HER2 expression is dependent on the type of brain tumors. High expression of HER2 in high-grade astrocytoma may be useful for therapeutic purposes. The future research is needed to confirm these results with a large number of patients in different areas.
REVIEW | doi:10.20944/preprints202307.1501.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: glial cells; astrocytes; oligodendrocytes; NG2 glia; microglia; human brain; ischemic brain injury; transcription factors
Online: 21 July 2023 (10:28:46 CEST)
There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis both under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their known proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, proliferation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation of the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving post-stroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.
ARTICLE | doi:10.20944/preprints202301.0377.v4
Subject: Physical Sciences, Condensed Matter Physics Keywords: quantum-classical dynamics; quantum brain; open quantum systems; neuroscience; electromagnetic brain stimulation; clinical psychology
Online: 31 March 2023 (04:29:56 CEST)
The study of the human psyche has elucidated a bipartite structure of logic reflecting the quantum--classical nature of the world. Accordingly, we posited an approach toward studying the brain by means of the quantum--classical dynamics of a mixed Weyl symbol. The mixed Weyl symbol can be used to describe brain processes at the microscopic level and, when averaged over an appropriate ensemble, can provide a link to the results of measurements made at the meso and macro scale. Within this approach, quantum variables (such as, for example, nuclear and electron spins, dipole momenta of particles or molecules, tunneling degrees of freedom, and so on) can be represented by spinors, whereas the electromagnetic fields and phonon modes can be treated either classically or semi-classically in phase space by also considering quantum zero-point fluctuations. Quantum zero-point effects can be incorporated into numerical simulations by controlling the temperature of each field mode via coupling to a dedicated Nos\'e-Hoover chain thermostat. The temperature of each thermostat was chosen in order to reproduce quantum statistics in the canonical ensemble. In this first paper, we introduce a general quantum--classical Hamiltonian model that can be tailored to study physical processes at the interface between the quantum and the classical world in the brain. While the approach is discussed in detail, numerical calculations are not reported in the present paper, but they are planned for future work. Our theory of brain dynamics subsumes some compatible aspects of three well-known quantum approaches to brain dynamics, namely the electromagnetic field theory approach, the orchestrated objective reduction theory, and the dissipative quantum model of the brain. All three models are reviewed.
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: brain injuries; traumatic brain injury; children; diversity; student-led; participant-focused; recruitment; sample; methods
Online: 7 July 2020 (04:42:39 CEST)
The advancement of the pediatric traumatic brain injury (TBI) knowledge base requires biospecimens and data from large samples. This study seeks to describe a novel clinical research modality to establish best practices for enrolling a diverse pediatric TBI population and quantifying key information on enrollment into biobanks. Screening form responses were standardized and cleaned through Google Sheets. Data was used to analyze total individuals at each enrollment stage. R was utilized for final analysis, including chi-square goodness of fit and proportion statistical tests, to determine further significance and relationships. Issues throughout data cleaning shed light on limitations of the consent modality. Results suggest that through a diverse research team, the recruited sample exceeds traditional measures of representation (e.g. sex, race, ethnicity). Sex demographics of the study are representative of the local population. Screening for candidates is critical to the success of the consent modality. The consent modality may be modified to increase diversity of study population and accept bilingual candidates. Researchers must implement best practices, including increasing inclusivity of bilingual populations, utilizing technology, and improving participant follow-up, to improve health disparities for understudied clinical populations.
Subject: Social Sciences, Behavior Sciences Keywords: emotion recognition; EEG signal decoding; brain anticipatory activity; machine learning; emotion related brain activity
Online: 31 December 2019 (10:05:27 CET)
Machine Learning (ML) approaches have been fruitfully applied to several classification problems of neurophysiological activity. Considering the relevance of emotion in human cognition and behaviour, ML found an important application field in emotion identification based on neurophysiological activity. Nonetheless, the literature results present a high variability depending on the neuronal activity measurement, the signal features and the classifier type. The present work aims to provide new methodological insight on ML applied to emotion identification based on electrophysiological brain activity. For this reason, we recorded EEG activity while emotional stimuli, high and low arousal (auditory and visual) were provided to a group of healthy participants. Our target signal to classify was the pre-stimulus onset brain activity. Classification performance of three different classifiers (LDA, SVM and kNN) was compared using both spectral and temporal features. Furthermore, we also contrasted the classifiers performance with static and dynamic (time evolving) features. The results show a clear increased in classification accuracy with temporal dynamic features. In particular, the SVM classifiers with temporal features showed the best accuracy (63.8 %) in classifying high vs. low arousal auditory stimuli.
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: basal ganglia; dopamine; subthalamic nucleus; Parkinson's disease; brain learning; cholinergic interneurons; deep brain stimulation
Online: 31 May 2019 (11:24:42 CEST)
The basal ganglia (BG) are a central component of the brain, crucial to the initiation, execution and learning of adaptive actions. The BG are the major site of the action of dopamine. An important aspect of the BG architecture is the existence of two paths, direct and indirect, having different projection targets and dopamine receptor expression. To understand the BG, dopamine, and related disorders, it is imperative to understand the two paths. The standard account used in neuroscience research for decades posits that the role of the direct path is to support movements, while that of the indirect path is to suppress unselected or completed movements. This account is contradicted by converging evidence. Here, we explain why the arguments supporting the standard account are flawed, and present a new account, in which the role of the indirect path is completely opposite: to support automated execution. During acute events, the direct path allows coarse responses. These are refined by competition, and the resulting focused response is executed and learned by the indirect path, assisted by cholinergic interneurons and the subthalamic nucleus (STN). The new account allows a novel understanding of the symptoms of Parkinson's disease, in particular tremor and rigidity, and of its treatment by STN deep brain stimulation.
ARTICLE | doi:10.20944/preprints201609.0126.v2
Subject: Computer Science And Mathematics, Computer Science Keywords: Brain-computer interface (BCI); visual motion perception; neurotechnology application; EEG; realtime brain signal decoding
Online: 4 October 2016 (14:43:48 CEST)
The paper presents a study of two novel visual motion onset stimulus-based brain–computer interfaces (vmoBCI). Two settings are compared with afferent and efferent to a computer screen center motion patterns. Online vmoBCI experiments are conducted in an oddball event–related potential (ERP) paradigm allowing for “aha–responses” decoding in EEG brainwaves. A subsequent stepwise linear discriminant analysis classification (swLDA) classification accuracy comparison is discussed based on two inter–stimulus–interval (ISI) settings of 700 and 150 ms in two online vmoBCI applications with six and eight command settings. A research hypothesis of classification accuracy non–significant differences with various ISIs is confirmed based on the two settings of 700 ms and 150 ms, as well as with various numbers of ERP response averaging scenarios.The efferent in respect to display center visual motion patterns allowed for a faster interfacing and thus they are recommended as more suitable for the no–eye–movements requiring visual BCIs.
ARTICLE | doi:10.20944/preprints202209.0137.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Chronic geriatric inflammation; machine learning C4.5 classification; brain ventricular volumes; recent fall; subconcussive brain trauma
Online: 9 September 2022 (13:05:28 CEST)
A chronic activated pro-inflammatory cytokine network (“inflamm-aging”) may amplify the neurodegenerative effects of a fall induced brain trauma in geriatric subjects. Our research aimed to evaluate how a trained machine learning algorithm may predict recent antecedent falls based only on specific serologic cytokines network analysis and how the consequences of these falls can be substantiated on standard head MRIs. All 279 subjects included in our study were selected from the ADNI1 dataset and all had a mild cognitive impairment diagnostic at the ADNI1 study baseline. A “train group” was built and included 14 subjects with a history of a recent, simple, standing-level fall. These were carefully matched with 14 similar subjects without any antecedent trauma. The “test group” included 251 subjects, all without any history of recent fall. The machine learning algorithm (classic C4.5 decision tree) was trained to detect a pattern of variation in 23 clinically relevant cytokines in relation with an antecedent fall. Changes in five cytokines (matrix metalloproteinase-7, eotaxin-1, interleukin-3, interleukin-8 and matrix metalloproteinase-9) were used for fall prediction in the “test” group. Once trained, the algorithm predicted a recent fall in 119 cases from the test group. The mean brain ventricular volume that was significantly different between fall/non-fall subgroups (41645.5±10337.2 vs 27127.3±6749.4 mm3, p=0.005) remained significant in the test group, after prediction between (41544.24±17343.4 vs 34553.5±10543.2 mm3, p=0.042). The hippocampus mean volume was also significantly different between in the test group (6297.3±1080.1 vs 6745.9±1123.7, p=0.0015). A significant brain ventricular difference was observed in the “65<y.o.” subgroup (p=0.04). If confirmed by larger prospective studies, our findings may increase the precision of the neuro-cognitive assessments in geriatric subjects.
ARTICLE | doi:10.20944/preprints201812.0082.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Brain injury, coma, consciousness, cognitive motor dissociation, disorders of consciousness, ethics, neurorehabilitation, traumatic brain injury
Online: 6 December 2018 (10:05:52 CET)
Background: The vegetative state (VS)/unresponsive wakefulness syndrome (UWS) denotes brain-injured, awake patients who are seemingly without awareness. Still, up to 15% of these patients show signs of covert consciousness when examined by functional magnetic resonance imaging (fMRI) or EEG, which is known as cognitive motor dissociation (CMD). Most experts prefer the term unresponsive wakefulness syndrome to avoid the negative connotations associated with vegetative state and to highlight the possibility for CMD. However, the perception of VS/UWS by the public has never been studied systematically. Methods: Using an online crowdsourcing platform, we recruited 1297 participants from 32 countries. We investigated if vegetative state and unresponsive wakefulness syndrome might have a different influence on attitudes towards VS/UWS and CMD. Results: Participants randomized to be inquired about the vegetative state believed that CMD was less common (mean estimated frequency in unresponsive patients 38.07% ± SD 25.15) than participants randomized to unresponsive wakefulness syndrome (42.29% ± SD 26.63; p=0.016). Attitudes towards treatment withdrawal were similar. Most participants preferred unresponsive wakefulness syndrome (60.05%), although a sizeable minority favored vegetative state (24.21%; difference 35.84%, 95% CI 29.36 to 41.87; p<0.0001). Searches on PubMed and Google Trends revealed that unresponsive wakefulness syndrome is increasingly used by academics but not lay people.Discussion: Simply replacing vegetative state with unresponsive wakefulness syndrome may not be fully appropriate given that 1 of 4 prefer the first term. We suggest that physicians take advantage of the controversy around the terminology to explain relatives the concept of CMD and its ethical implications.
ARTICLE | doi:10.20944/preprints202309.2114.v1
Subject: Biology And Life Sciences, Aging Keywords: Human; lifespan; aging; consciousness; brain; integration
Online: 30 September 2023 (17:55:59 CEST)
Human longevity is an important but difficult goal due to the extreme complication of human body. If people could repeatedly transfer their consciousness from old bodies to new ones, their lifespan might be prolonged extremely. However, there are several difficulties which prevent the achievement of such a technique. In this paper, we propose an approach that can transfer human consciousness indirectly, and avoid or significantly relieve those difficulties. The strategy of our approach is to integrate the consciousnesses of two bodies (old and new) into a unique consciousness. By doing so, the consciousness is extended to the new body. After that, the consciousness shrinks and remains in the new body when the old body dies. This may also apply to integrating more than two bodies of human, or animal, or even across different species. After investigating thousands of literatures, we find quite strong evidence (related discoveries and technologies) that can support the proposed approach and its advantages. Beside prolonging human lifespan, the approach could also have other meaningful applications.
REVIEW | doi:10.20944/preprints202309.0005.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: ADHD, childhood, diagnosis, brain, functional connectivity
Online: 1 September 2023 (13:03:41 CEST)
Attention Deficit Hyperactivity Disorder (ADHD) it is known as a neuropsychiatric disorder. Anatomicaly components with implications in this previously mentioned disorder, are the anterior cingulate gyrus and dorsolateral prefrontal cortex (DLFPC) that are are found having a role in appearing this disease. ADHD is associated with cognitive and functional deficits that relate to diffuse abnormalities in the brain. ADHD is a specific pathology in children but may persisit to youth and also not so hard to find to adults.Till now, hard to find the curative treatment knowing ADHD as a neuropsychiatric disorder with enlarge unknown scientific points. Genetic and environmental component play an important role in diagnosis. Patients life style, a relevant history of individual geneticsand environmental factors are important in diagnosisThe management of ADHD, is also an important part togeter with future trends.
ARTICLE | doi:10.20944/preprints202308.1731.v1
Subject: Biology And Life Sciences, Biophysics Keywords: Quantum entanglement, brain, Immediate information transfer
Online: 24 August 2023 (09:57:34 CEST)
A human brain can communicate with another one’s brain using quantum entanglement. Similar particles can entangle without interaction. Sensory communication between two individuals from far distances is still not known. Former studies primarily have been performed regarding brain neurons' quantum behavior. The test was performed on two individuals far from each other. These individuals were put under the same music on the basis of brain neuroplasticity property. By activating the brain reward system, aligned thinking was time scheduled in these individuals’ brains. On the basis of entanglement, compressed information was sent and received between these two individuals.
ARTICLE | doi:10.20944/preprints202304.0027.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: brain tumour; oncolytic virus; receptor; therapy
Online: 3 April 2023 (13:31:42 CEST)
Glioblastoma (GBM) is the most common and aggressive adult brain cancer with an average survival rate of around 15 months in patients receiving standard treatment. Oncolytic adenovirus expressing therapeutic transgenes represent a promising alternative treatment for GBM. Of the many human adenoviral serotypes described to date, adenovirus 5 (Ad5) has been most utilized clinically and experimentally. However, the use of Ad5 as an anti-cancer agent may be hampered by naturally high seroprevalence rates to Ad5 coupled with infection of healthy cells via native receptors. To explore whether alternative natural adenoviral tropisms are better suited to GBM therapeutics, we pseudotyped an Ad5 based platform with the fiber knob protein from alternative serotypes. We demonstrate that the adenoviral entry receptors coxsackie and adenovirus receptor (CAR) and CD46 are highly expressed by both GBM and healthy brain tissue, whereas Desmoglein 2 (DSG2) is expressed at low level in GBM. We demonstrate that adenoviral pseudotypes, engaging CAR, CD46 and DSG2, effectively transduce GBM cells. However, the presence of these receptors on non-transformed cells presents the possibility of off-target effects and therapeutic transgene expression in healthy cells. To enhance specificity of transgene expression to GBM, we assessed the potential for tumour specific promoters hTERT and survivin to drive reporter gene expression selectively in GBM cell lines. We demonstrate tightly GBM specific transgene expression using these constructs, indicating that the combination of pseudotyping and tumour specific promoters approaches may enable the development of efficacious therapies better suited to GBM.
ARTICLE | doi:10.20944/preprints202212.0183.v1
Subject: Medicine And Pharmacology, Orthopedics And Sports Medicine Keywords: hypothermia; sportstr; brain injury; rehabilitation; hyperthermia
Online: 9 December 2022 (14:50:39 CET)
Sports traumatic brain injury (TBI) accounts for up to 20% of all sports injuries, and the number of cases is growing year by year due to an increase in the number of people involved in sports, the growing popularity of extreme and contact sports, as well as a high level of motivation to achieve record results. Mild TBI dominates, which can provoke the development of a very wide range of complications and negative consequences. In the programs for the prevention of complications and the rehabilitation of athletes after TBI, TBI features are not sufficiently considered, which significantly differ from household, road or criminal injuries. There are no instrumental methods for diagnosing the severity of the injury. Sports TBI is characterized by repeated frequent TBI, elevated body and brain temperature, peripheral redistribution of blood flow and hypocapnia, which significantly affect cerebral blood flow. Brain injury is an independent cause of the development of cerebral hyperthermia, which significantly worsens the consequences of TBI. To diagnose sports TBI, the method of microwave radiometry of the brain (MWR) can be used. For the prevention of complications, the technology of craniocerebral hypothermia (CCH), which allows for to reduce of physical general and cerebral hyperthermia, and increases the resistance of cerebral cortex neurons to hypoxia and trauma could be used However, these approaches in sports medicine are used sporadically, which, is due to the lack of awareness of coaches and doctors of sports teams. The purpose of the review is to present MWR and CCH in sports TBI.
ARTICLE | doi:10.20944/preprints202209.0307.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: emotional intelligence; brain injury; cognitive impairment
Online: 20 September 2022 (13:14:54 CEST)
Background: Cognitive-behavioral alterations can occur after an acquired brain injury. It is a stressful situa-tion for patient and relatives. Objectives: To develop and evaluate a synchronous online training program on emotional intelligence (EI) for caregivers of adult patients with cognitive-behavioral impairment due to acquired brain injury. Methods: A quasi-experimental study was designed, a target population of ten caregivers attended to a one-month virtual synchronous course about EI. The emotional status of caregivers was registered one-month-previous and one-month-post program using comparative measures: The Trait Meta-Mood Scale (TMMS-24) and the Positive and Negative Affect Schedule (PANAS). Results: Median age of the ten caregivers was 48 years, 80% of women with a median care-time of 6 years. 50% of them were spouses of the patients. 60% of the patients were affected by stroke (hemorrhagic or ischemic cause). The main cognitive impairment of the patients reported by relatives was memory deficit. After re-ceiving training, favorable changes were found regarding emotional affect measured with the PANAS, both positive (increase) and negative (decrease), as well as with the TMMS-24-mood-repair area (p < 0.05). Conclusions: Training in EI helps caregivers to make their mood more positive and improve aspects of their emotional intelligence such as emotional regulation.
ARTICLE | doi:10.20944/preprints202208.0480.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: psychiatric disease; brain injury; chloride transporter
Online: 29 August 2022 (09:36:50 CEST)
Background. Traumatic brain injury (TBI) is the main cause of disabilities over the industrialized countries. Cognitive decline appears in the chronic phase of the pathology consecutively to cellular and molecular processes. Here we described the use of KCC2, a neuronal-specific potassium-chloride transporters as potent biomarker to predict cognitive dysfunctions after TBI. Methods. Using neuronal and total exosomes collection from blood serum in control and TBI subjects we were able to anticipate the decline of cognitive performance. Results. After TBI, we observed a significative and persistant loss of KCC2 expression in the blood exosomes that is correlated to changes in network activity and cellular processes such as secondary neurogenesis. Also we correlated this KCC2 loss in expression to the appearance of the cognitive decline observed in mice and more particularly we correlate the KCC2 loss of expression to the appearance of the depressive-like behavior. Conclusion. According to our protocol, we were able to confirm our previous findings in agreement with the potential therapeutic effect of bumetanide in the prevention of the post traumatic depression after TBI, by restoring the KCC2 expression thus preventing the massive neuronal death of interneurons and the secondary neurogenesis effect observed in such model.
ARTICLE | doi:10.20944/preprints202206.0002.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Human brain evolution; complex systems theory
Online: 1 June 2022 (03:37:03 CEST)
Scientific theories on the functioning and dysfunction of the human brain require a good understanding of both its development — before and after birth, and through maturation to adulthood — and its evolution from the ancestral primate brain. Adopting a complex-systems approach, here we propose that the apparent uniqueness of humans’ cognitive capacities might best be understood as emerging from multiple nested “virtuous cycles.” In particular, we propose that the intimate link that exists between oxygen metabolic loops, cortical expansion, and ultimately cognitive and social demands is a key driver of genetic developmental programs for the human brain. Overall, our proposed evolutionary model makes explicit mechanistic links between metabolism, molecular and cellular brain heterogeneity, and behaviour that may in time provide a clearer understanding of brain developmental trajectories and their disorders.
ARTICLE | doi:10.20944/preprints202205.0006.v1
Subject: Biology And Life Sciences, Biophysics Keywords: structured illumination; fluorescence; brain; multi-camera
Online: 4 May 2022 (12:24:22 CEST)
Fluorescence microscopy provides an unparalleled tool for imaging biological samples. However, producing high-quality volumetric images quickly and without excessive complexity remains a challenge. Here, we demonstrate a simple multi-camera structured illumination microscope (SIM) capable of simultaneously imaging multiple focal planes, allowing for the capture of 3D fluorescent images without any axial movement of the sample. This simple setup allows for the acquisition of many different 3D imaging modes, including 3D time lapses, high-axial-resolution 3D images, and large 3D mosaics.
COMMUNICATION | doi:10.20944/preprints202203.0152.v1
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: SPME; CBS-MS; brain tumors; lipidomics
Online: 10 March 2022 (14:16:39 CET)
Brain tumors are neoplasms with one of the highest mortality rates. Therefore, the availability of methods that allow the quick and effective diagnosis of brain tumors and selection of appropriate treatments is of critical importance for patient outcomes. In this study, coated blade spray-mass spectrometry (CBS-MS), which combines the features of microextraction and fast ionization methods, is applied for the analysis of brain tumors. In this approach, a sword-shaped probe is coated with a sorptive material to enable the extraction of analytes from biological samples. The analytes are then desorbed using only a few microliters of solvent, followed by the insertion of the CBS device into the interface on the mass spectrometer source. The results of this proof-of-concept experiment confirmed that CBS coupled to high-resolution mass spectrometry (HRMS) enables the rapid differentiation of two histologically different lesions: meningiomas and gliomas. Moreover, quantitative CBS-HRMS/MS analysis of carnitine, the endogenous compound, previously identified as discriminating metabolite showed good reproducibility with the variation below 10% when using a standard addition calibration strategy and deuterated internal standards for correction. The resultant data show that the proposed CBS-MS technique can be useful for on-site qualitative and quantitative assessments of brain tumor metabolite profiles.
COMMUNICATION | doi:10.20944/preprints202104.0011.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: laterality; brain; hemisphere; asymmetry; activity; biofeedback
Online: 1 April 2021 (10:52:07 CEST)
In the current pilot study, we attempt to find out how double neurofeedback influences functional hemispheric asymmetry and activity. We examined 30 healthy participants (8 males; 22 females, mean age = 29; SD= 8). To measure functional hemispheric asymmetry and activity, we used computer laterometry in the ‘two-source’ lead-lag dichotic paradigm. Double biofeedback included 8 minutes of EEG oscillation recording with five minutes of basic mode. During the basic mode, the current amplitude of the EEG oscillator gets transformed into feedback sounds while the current amplitude of alpha EEG oscillator is used to modulate the intensity of light signals. Double neurofeedback did not directly influence the asymmetry itself but accelerated individual sound perception characteristics during dichotic listening in the preceding effect paradigm. Further research is needed to investigate the effect of double neurofeedback training on functional brain activity and asymmetry taking into account participants’ age, gender, and motivation.
REVIEW | doi:10.20944/preprints202010.0311.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Parenting; brain; development; fmri; child development
Online: 14 October 2020 (15:22:41 CEST)
Parenting has been robustly associated with offspring psychosocial development, and these effects are likely reflected in brain development. However, the claim that parenting influences offspring brain development in humans, as measured by structural and functional Magnetic Resonance Imaging (MRI), is subject to numerous methodological limitations. To interpret the state of the parenting and brain development literature, we review these limitations. Four limitations are common. First, most literature has been cross-sectional. Where longitudinal, studies rarely included multiple assessments of brain structure or function, precluding measurement of actual brain development. Second, parenting has largely been measured via selfor parent-report, as opposed to observational assessment. Third, there has been a focus on extreme forms of developmental adversity which do not necessarily lie on a continuum with normative parenting. Fourth, although not a limitation per se, studies have generally focused on negative as opposed to positive parenting behaviours. While not all studies are subject to all these limitations, the study of parenting in relation to offspring brain development is in its infancy.
ARTICLE | doi:10.20944/preprints201810.0299.v1
Subject: Biology And Life Sciences, Biophysics Keywords: lines; brain; topology; curvature; Dickinsonia; fMRI
Online: 15 October 2018 (10:36:18 CEST)
Geometry deals both with analogical thinking and physical/biological observables. Naïve, common-sense descriptions of objects’ shapes and systems’ trajectories in geometric phase spaces may help experimental investigation. For example, very different biological dynamics, as the developmental growth patterns of the oldest known animal (the extinct Dickinsonia) and the human brain electric oscillations, display a striking analogy: when encompassed in abstract geometric spaces, their paths describe the same changes in curvature: from convex, to flat, to concave and vice versa. This dynamical behavior, anticipated by Nicholas de Cusa in his analogical account of “coincidentia oppositorum” (1440), helps to describe widespread biological paths in the manageable terms of concave, flat and convex curves on donut-like structures. Every trajectory taking place on such toroidal manifolds can be located, through a topological technique called Hopf fibration, into a four-dimensional space. We discuss how the correlation between Hopf fibration and Navier-Stokes equations allows us to treat the above-mentioned biological and neuroscientific curved paths in terms of flows taking place into a viscous fluid medium that can be experimentally assessed and quantified.
ARTICLE | doi:10.20944/preprints201809.0403.v1
Subject: Arts And Humanities, Philosophy Keywords: philosophy; epistemology; empirio-criticism; neuroscience; brain
Online: 20 September 2018 (08:04:55 CEST)
The French-Swiss Professor in inductive philosophy Richard Avenarius (1843-1896), the father of empirio-criticism together with Ernst Mach, is one of the most underrated and misunderstood philosophers ever. It mostly depends upon his terminology, which displays an insurmountable difficulty. However, influenced by the most innovative proposals of his times of transition between the idealistic/rationalist legacies and the new Materialism/scientific interpretation of reality – i.e, by cultural evolutionism, linguistics, biomechanics, entropy/energy and, above all, by the newborn experimental psychology-, he produced a complete system of philosophy and innovative methods of investigation of the laws of knowledge. Hints (chunk, scrap, fragments) of his original ideas can be found not only in philosophers of mind after him - such as Gestalt, phenomenalism, behaviourism, functionalism and cybernetics, autopoiesis, dynamical systems theory, embedded/embodied mind, free-energy principle of the brain – but also in recent neuroscientific theories – nervous transduction, electric spikes, cracking of neural code, multisensory integration -. Our aim is to provide the first chronological English summary of his masterpiece, the “Kritik”, to give the possibility to the (almost) totally unaware English speakers to appreciate such a neglected and innovative thinker.
REVIEW | doi:10.20944/preprints201808.0223.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: brain blood barrier; endothelial dysfunction; neurodegeneration
Online: 13 August 2018 (08:59:21 CEST)
The main neurovascular unit of the Blood Brain Barrier (BBB) consists of a cellular component, which includes endothelial cells, astrocytes, pericytes, microglia, neurons and oligodendrocytes, as well as a non-cellular component resulting from the extracellular matrix. The endothelial cells are the major vital component of the BBB able to preserve the brain homeostasis; these cells are situated along the demarcation line between the bloodstream and the brain. Therefore, an alteration or the progressive disruption of the endothelial layer may clearly impair the brain homeostasis. The proper functioning of the brain endothelial cells is generally ensured by two elements: 1) the presence of junction proteins; 2) the preservation of a specific polarity involving an apical-luminal and a basolateral-abluminal membrane. In view of the above, this review intends to identify the molecular mechanisms underlying BBB function and their changes occurring in early stages of neurodegenerative processes in order to develop novel therapeutic strategies aimed to counteract neurodegenerative disorders.
REVIEW | doi:10.20944/preprints201808.0027.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Hedgehog; Ischemia; Heart; Brain; Skeletal muscle
Online: 1 August 2018 (16:31:01 CEST)
Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.
ARTICLE | doi:10.20944/preprints201710.0073.v1
Subject: Computer Science And Mathematics, Data Structures, Algorithms And Complexity Keywords: graph alignment; brain network; human connectome
Online: 12 October 2017 (04:07:33 CEST)
A growing area in neurosciences is focused on the modeling and analysis the complex system of connections in neural systems, i.e. the connectome. Here we focus on the representation of connectomes by using graph theory formalisms. The human brain connectomes are usually derived from neuroimages; the analyzed brains are co-registered in the image domain and brought to a common anatomical space. An atlas is then applied in order to define anatomically meaningful regions that will serve as the nodes of the network - this process is referred to as parcellation. Recently, it has been proposed to perform atlas-free random brain parcellation into nodes and align brains in the network space instead of the anatomical image space to define network nodes of individual brain networks. In the network domain, the question of comparison of the structure of networks arises. Such question is tackled by modeling the comparison of brain network as a network alignment (NA) problem. In this paper, we first defined the NA problem formally, then we applied three existing state of the art of multiple alignment algorithms (MNA) on diffusion MRI-derived brain networks and we compared the performances. The results confirm that MNA algorithms may be applied in cases of atlas-free parcellation for a fully network-driven comparison of connectomes.
REVIEW | doi:10.20944/preprints202310.1786.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Intracranial compliance; Viscous component; Time-dependent disorders; Brain disorder; Strain rate; Cerebrospinal fluid; Brain biomechanics; Clinical application.
Online: 27 October 2023 (10:33:52 CEST)
Intracranial compliance (ICC) plays a pivotal role in understanding the underlying mechanisms of various brain disorders and is of great clinical importance. Therefore, addressing the challenges in practical application of ICC is crucial for neurosurgeons. This study explored the significance of ICC assessment considering the time-dependency of specific brain disorders through two distinct approaches: short and large time elapsed (TE) in measuring volume or intracranial pressure (ICP) changes in the ICC equation (∆Volume/∆ICP). Variations in ICC values were observed across various ICC assessment methods and different TE values. Notably, the compensatory response of the brain exhibited non-monotonic and variable changes in a large TE for certain brain disorders, diverging from patterns observed in short TE assessments. Furthermore, the recovery behavior of the brain changed under different brain disorders when exposed to short and long TE conditions. These findings emphasized the dynamic nature of ICC and provided valuable insights into the correct practical assessment of ICC by selecting the appropriate TE, as well as considering the differences in strain rates and loading durations on the brain in different brain disorders. These insights also shed light on the reasons why, despite its clinical significance, ICC monitoring has not yet become a standard component of clinical care, unlike ICP monitoring.
REVIEW | doi:10.20944/preprints202309.0428.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: NK1 receptor; Substance P; Neuroinflammation; Blood-brain barrier; Traumatic brain injury; Stroke; CNS infection; NK1 receptor antagonist
Online: 7 September 2023 (03:59:49 CEST)
Neuroinflammation is considered to be a significant component in a range of neuropathologies. Unfortunately, whilst its role is well recognized, the options for therapeutic intervention are limited. As such, there is a need to identify novel targets in order to increase treatment options. Given its role as both a neurotransmitter and an immune modulator, substance P and its NK1 receptor have been widely studied as a potential therapeutic target. There is evidence that NK1 receptor antagonists may exert beneficial effects in a range of conditions, including traumatic brain injury and stroke. Blocking the NK1 receptor has been shown to reduce blood-brain barrier dysfunction, reduce cerebral oedema, and reduce the levels of pro-inflammatory cytokines. These actions are associated with improved survival and functional outcomes. The NK1 receptor has also been shown to be involved in the inflammatory reaction to CNS infection, and hence antagonist may have some benefit in reducing infection-driven inflammation. However, the NK1 receptor may also play a role in the host immune response to infection, and so here, the potential beneficial and detrimental effects need to be carefully balanced. As such, the purpose of this review is to provide a summary of the involvement of substance P in acute inflammation, particularly in the context of traumatic brain injury and stroke.
REVIEW | doi:10.20944/preprints202108.0237.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Alzheimer’s disease; cytokines; chemokines; neuroinflammation; neurotrophic factors; pathophysiology; Blood brain barrier; mild cognitive impairment; brain health; therapeutics
Online: 10 August 2021 (15:49:12 CEST)
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized mainly by the gradual decay in neuronal function as a consequence of diverse degenerating events primarily including mitochondria dysfunction and cascades of neuro-immune reactions. Besides the acquired harmful reactive oxygen species (ROS), neurotoxins, and amyloid-beta (Aβ) and TAU pathologies in neurons, accumulating evidence with time underlined the roles of cytokines and growth factors in the AD pathogenesis. It may help us in evaluating the propensities and specific mechanism(s) of cytokines and factors impacting neuron upon apoptotic decline. Proinflammatory cytokines often induce inflammation in AD and AD-like pathogenesis in response to the apoptotic scenarios where some growth factors are involved in cytokinetic reactions to activate microglia and causing inflammation in AD. In this report, we comprehensively reviewed role of cytokines and chemokines in immune response to AD and neuropsychiatry. We provided insights into the neuroinflammation and the role of diverse factors including the pro-/anti-inflammatory cytokines, APP, TAU phosphorylation, glycation end products, complement system, and the role of glial cells. Also, we discussed the pathogenic and protective role of macrophage migration inhibitory factors, choroid plexus-, neurotrophic- and hematopoietic -related growth factors in AD. We further shed light on the availability and accessibility of the cytokines across the blood-brain barrier in AD pathophysiology. Taken together, the emerging role of these factors in AD pathology emphasized the importance of building novel strategies for an effective therapeutic/neuropsychiatric management of AD in clinics.
REVIEW | doi:10.20944/preprints202012.0314.v1
Subject: Social Sciences, Psychology Keywords: Very mild Traumatic Brain Injury; Animal models (rodents); Post-concussion syndrome; neuro-behavioral changes; “inflammaging”; brain apoptosis
Online: 14 December 2020 (09:33:51 CET)
Post-concussion syndrome, recently recognized as a complication of mild traumatic brain injury, is considered a consequence of the summative effect of multiple concussions received over lifetime. In elderlies, the main mild brain trauma mechanism is fall (low impact force). Many falls are often not reported or noticed but may generate serious medical and medico-legal consequences. Our research question was to find if a single, very mild brain trauma can induce neuro-behavioral consequences in elderlies. One database was queried (PubMed – MeSH terminology) looking for histopathological, neuro-cognitive and behavioral changes that can be generated by sub-concussional trauma in senescent rodents, in comparison with young animals. 41 published research articles were selected. 17 of them used very mild brain trauma in young and senescent animals, in the same experiment (6 rats and 11 mice). 24 articles evaluated the effect of sub-threshold brain trauma in adult animals (no control group). Five trauma models were used (blast models were excluded). Neuro-inflammatory changes were detected immediate after very mild primary impact. In young animals, observed pathology disappeared fast (after 3 to 7 days). Increased apoptosis, mild axonal injury in white matter tracts plus maladaptive astrogliosis and microglial activation was stronger in aged animals, persisted over time (8 months) and significantly altered animals’ cognition and behavior. Associated preexisting pathology (hypertension, tau protein deposits, microbleeds, reactive inflammation) was often responsible for amplification of the primary impact results. As translation of observation is the weak spot of pathology and behavior animal research, further investigation is needed before to conclude that even a single, very mild brain trauma may have medical consequences on human senescent brain.
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Brain death; posterior fossa; brainstem death; ancillary tests; EEG; evoked potentials
Online: 3 August 2020 (01:22:49 CEST)
Background: New controversies have raised on brain death (BD) diagnosis when lesions are localized in the posterior fossa. Objective: To discuss the particularities of diagnosis BD in patients with posterior fossa lesions. Material and Methods. The author made a systematic review of literature on this topic. Results and Conclusions: A supratentorial brain lesion usually produces a rostrocaudal transtentorial brain herniation, resulting in forebrain and brainstem loss of function. In secondary brain lesions [i.e., cerebral hypoxia], the brainstem is also affected like the forebrain. Nevertheless, some cases complaining posterior fossa lesions [i.e., basilar artery thrombotic infarcts, or hemorrhages of the brainstem and/or cerebellum] may retain intracranial blood flow and EEG activity. In this article I discuss that if a posterior fossa lesion does not produce an enormous increment of intracranial pressure, a complete intracranial circulatory arrest does not occur, explaining the preservation of EEG activity, evoked potentials, and autonomic function. I also address Jahi McMath, who was declared braindead, but ancillary tests, performed 9 months after initial brain insult, showed conservation of intracranial structures, EEG activity, and autonomic reactivity to “Mother Talks” stimulus, rejecting the diagnosis of BD. Jahi McMath’s MRI study demonstrated a huge lesion in the pons. Some authors have argued that in patients with primary brainstem lesions it might be possible to find a in some cases partial recover of consciousness, even fulfilling clinical BD criteria. This was the case in Jahi McMath.
REVIEW | doi:10.20944/preprints202311.1530.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Epigenetics; DNA; Histones; Brain; Neurons; Development; Neurodegeneration
Online: 23 November 2023 (12:55:24 CET)
Epigenetic changes are changes in gene expression that do not involve alterations to the basic DNA sequence. These changes lead to establishing a so-called epigenetic code that dictates which and when genes are activated, thus orchestrating gene regulation and playing a central role in development, health, and disease. The brain, being for the most formed by cells that do not undergo a renewal process through life, is highly prone to the risk of alterations leading to neuronal death and neurodegenerative disorders, mainly at late age. Here we review the main epigenetic modifications that have been described in the brain, with particular attention to those related to the onset of developmental anomalies or neurodegenerative conditions and/or occurring in old age. DNA methylation and several types of histone modifications (acetylation, methylation, phosphorylation, ubiquitination, sumoylation, lactylation, and crotonylation) are major players in these processes. They are directly or indirectly involved in the onset of neurodegeneration in Alzheimer’s or Parkinson’s disease. Therefore, this review briefly describes the role of these epigenetic changes in the mechanisms of brain development, maturation, and aging and some of the most important factors dynamically regulating or contributing to these changes such as oxidative stress, inflammation, and mitochondrial dysfunction.
ARTICLE | doi:10.20944/preprints202311.1127.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: machine learning; application; classification; brain diseases; detection
Online: 17 November 2023 (15:32:16 CET)
During a multi-detector computed tomography (MDCT) examination, it is crucial to efficiently organize, store, and transmit medical images in DICOM standard, which requires significant hardware resources and memory. Our project processed large amounts of DICOM images by classifying them based on cross-section views that may carry important information about a possible diagnosis. We ensured that images were retained and saved in PNG format to optimize hardware resources while preserving patient confidentiality. Furthermore, we have developed a graphical, user-friendly interface that allows physicians to visualize specific regions of interest in a patient's brain where changes may indicate disease. Our proposed method enables quick classification of medical images into predefined classes of confirmed diseases of brain parenchyma, contributing to swift decision-making for further diagnosis for more precisely evaluating and characterizing brain changes, and it can lead to the rapid application of adequate therapy, which may result in better outcomes.
CASE REPORT | doi:10.20944/preprints202311.0568.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Brain Diseases; Inflammation; Steroids; Immunosuppressive Agents; MRI;
Online: 8 November 2023 (15:42:44 CET)
CLIPPERS which stand for Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, is a chronic inflammatory disorder of the central nervous system. The aetiology of CLIPPERS remains unclear, although its pathogenesis shows immune-mediated processes. The diagnosis of CLIPPERS is challenging without a specific biomarker hence, it is important to consider if both the clinical and radiological features are consistent with the diagnosis, or rather any other disease that mimics CLIPPERS. The Authors present a case of a 40-year-old Female patient diagnosed with CLIPPERS syndrome in India. Differential diagnosis, clinical and MRI characteristics of CLIPPERS syndrome, and treatment approaches are discussed.
REVIEW | doi:10.20944/preprints202311.0375.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: lipid; apolipoprotein; circadian clock; brain; neuron; hormone
Online: 6 November 2023 (17:42:18 CET)
The circadian clock is a 24-hour cycle within the body that regulates various factors, including sleep, body temperature, and hormone secretion. It allows the body to adjust to the light and dark cycle. Disruptions to the circadian rhythm are important risk factors for many diseases, including neurodegenerative illnesses. The central clock is controlled by the clock genes in the suprachiasmatic nucleus (SCN) of the brain, and one of the main functions of the circadian clock is to regulate lipid metabolism. There has been a lack of investigation on the circadian regulation of lipid metabolism-related apolipoprotein genes in the brain; thus, this study sought to summarize the rhythmic expression of clock genes and lipid metabolism-related apolipoprotein genes within the SCN of Mus musculus. Out of the 20 apolipoprotein genes that were studied by the published database, all 9 genes were highly expressed in the SCN. Most of the 6 genes showed rhythmic expression in the brain of mice, suggesting that the master clock might regulate them. The results, therefore, reveal a potential target for preventing and treating circadian disorders. We summarized most studies of lipid-related apolipoprotein genes within limited locations of the SCN and brain to further understand how disordered cerebral lipid metabolism causes multiple brain diseases and disorders. We reviewed recent studies, determined the unexplored questions, and identified a potential direction for further research.
ARTICLE | doi:10.20944/preprints202309.0370.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: memory model; brain model; ontology; statistical clustering
Online: 6 September 2023 (04:13:53 CEST)
This paper describes a memory model with 3 levels of information. The lower-level stores source data, is Markov-like and unweighted. Then a middle-level ontology is created from a further 3 phases of aggregating source information, by transposing from an ensemble to a hierarchy at each level. The ontology is useful for search processes and the aggregating process transposes the information from horizontal set-based sequences to more vertical typed-based clusters. The base memory is essentially neutral, where any weighted constraints or preferences should be sent by the calling module. This therefore allows different weight sets to be imposed on the same linking structure. The success of the ontology typing is open to interpretation, but the author would suggest that when clustering text, the result was types based more on use and context, for example, 'linking' with 'structure' or 'provide' with 'web,' for a document describing distributed service-based networks. This allows the system to economise over symbol use, where links to related symbols will be clustered together. The author then conjectures that a third memory substrate would be more neural in nature and would include functions or operations to be performed on the data, along with related memory information.
ARTICLE | doi:10.20944/preprints202308.0695.v1
Subject: Computer Science And Mathematics, Signal Processing Keywords: Brain network; Magnetoencephalogram; Granger causality; Kernel function
Online: 9 August 2023 (05:11:40 CEST)
Depression is one of the psychiatric disorders characterized by anxiety, pessimism, and suicidal tendencies, which seriously affect the quality of life of patients and their families. In this paper, we used polynomial-based kernel Granger causality values as network node connectivity indicators to construct brain networks for 5 depressed patients and 11 healthy individuals’ magnetoencephalogram(MEG) under positive, neutral, and negative emotional stimuli, respectively, and found that depressed patients had closer information exchange between frontal and occipital regions compared to healthy individuals and other brain regions, and fewer causal connections in parietal and central regions. Further analysis of the topological properties of the network revealed that depressed patients had higher mean degrees under negative stimuli (p=0.008)and lower mean clustering coefficients than healthy individuals(p=0.034). Comparing the mean degree and mean clustering coefficient of the same sample under different emotional stimuli, we found that depressed patients had the greater mean degree and mean clustering coefficient under negative stimuli than neutral and positive stimuli. We also found that patients’ feature path lengths under negative and neutral stimuli significantly deviated from small-world attributes. The results suggest that analysis of nuclear Granger causality-based brain networks can effectively characterize depression pathology.
ARTICLE | doi:10.20944/preprints202307.2052.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Artificial Intelligence; Gestational Age; Fetal Brain; MRI
Online: 31 July 2023 (03:07:23 CEST)
Abstract: Accurately predicting a fetus's gestational age (GA) is of utmost importance in prenatal care. This study aimed to develop an artificial intelligence (AI) model that can automatically predict GA using biometric measurements derived from fetal brain mag-netic resonance imaging (MRI). Additionally, we aimed to assess the significance of con-sidering different references when interpreting GA predictions. To achieve this, we obtained measurements such as Biparietal Diameter (BPD), Fron-to-occipital Diameter (FOD), and Head Circumference (HC) from a dataset comprising 52 normal fetal MRI cases with T2 Haste sequences from Rush University. Both manual and AI-based methods were utilized to acquire these measurements. We also employed three reference papers (Garel, Freq, and Bio) for comparison purposes. The results demonstrated a strong correlation between manual and AI measure-ments, indicating consistency between the two methods. The AI-based measurement of HC exhibited a higher correlation with actual values compared to BPD, FOD, and correct-ed BPD (BPDC). When comparing these measurements with GA in the Picture Archiving and Communication System (PACS), the differences varied depending on the reference used. Specifically, the differences ranged from 0.47 to 2.17 weeks for BPD, 0.46 to 2.26 weeks for FOD, and 0.75 to 1.74 weeks for HC. Furthermore, the Pearson correlation coeffi-cient analysis revealed that all correlation coefficients between PACS records and GA pre-dictions using different references were greater than 0.97. In conclusion, the AI model based on fetal brain MRI accurately predicts GA by uti-lizing BPD, FOD, and HC measurements. The AI approach, which involves combining line segments to calculate fetal head circumference, offers improved accuracy and con-venience compared to manual estimation. This study underscores the potential of AI models in accurately estimating gestational age and highlights their utility in prenatal care. By integrating AI as a valuable tool in prenatal care, we can enhance the accuracy, ef-ficiency, and decision-making involved in assessing fetal development and monitoring pregnancies using MRI measurements.
ARTICLE | doi:10.20944/preprints202307.1421.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Hydrocephalus; Brain Hemorrhage; Arteriovenous Malformation; Ventriculoperitoneal Shunt
Online: 21 July 2023 (02:27:00 CEST)
Hemorrhagic complications arising from ventricular drainage procedures are typically asymptomatic and of low volume. A particular subset of these complications known as Delayed Intracranial Hemorrhage (DICH) is however recognized for its particularly poor prognosis. We primarily aimed to identify epidemiological characteristics associated with DICH, to shed light on its occurrence and potential risk factors. To do so, we performed a retrospective analysis of a series of ten patients who presented with DICH in the context of a ruptured brain Arteriovenous Malformation (bAVM), and a systematic literature review of all DICH cases reported in the literature. Our ten patients showed delayed neurological deterioration after Ventriculoperitoneal Shunt (VPS) procedure, with a computed tomography (CT) scan revealing a DICH surrounding the ventricular catheter, distinct and away from the nidus of their previously ruptured bAVM. Four patients (40%) rapidly declined and passed away, three (30%) required surgical management and the remaining three (30%) demonstrated gradual clinical improvement with conservative management. In the literature, most patients presenting with DICH had hydrocephalus associated with neurovascular disorders (47% of cases), such as bAVM rupture in our present series. These constatations point out the significance of underlying pathologies potentially predisposing to these unusual complications.
TECHNICAL NOTE | doi:10.20944/preprints202306.0825.v1
Subject: Public Health And Healthcare, Physical Therapy, Sports Therapy And Rehabilitation Keywords: Cough Reflex; Acquired Brain Injury; capsaicin; dysphagia
Online: 12 June 2023 (10:42:59 CEST)
The cough assessment is fundamental in the weaning process as it gives information on the possibility to expel food and secretion from the airways. The majority of persons suffering from severe acquired brain injury (ABI) are not able to cough voluntarily due to severe motor deficits. In the present study, we evaluated the cough reflex in ABI patients using a new method based on a capsaicin spray stimulation test. 100 Healthy controls demographically matched with 50 ABI patients were included in this study. Clinical observations demonstrated robust cough response in both healthy controls and ABI patients, as well as the safety and tolerability of capsaicin spray stimulation. ABI patients with dysphagia were characterized by slower and delayed cough responses. Further studies are needed to validate this feasible, less-invasive, and simple-to-comprehend technique in inducing cough reflex. According to this preliminary evidence, we believe that this test might be translated into a simple and effective treatment to improve cough strength training reflexive cough modulation in ABI patients.
ARTICLE | doi:10.20944/preprints202306.0788.v1
Subject: Medicine And Pharmacology, Surgery Keywords: Craniofacial trauma; Traumatic Brain Injury; Concurrent diagnosis
Online: 12 June 2023 (07:31:13 CEST)
Background: Craniofacial injuries are thought to be commonly associated with traumatic brain injury (TBI), but there is conflicting evidence in the literature. The objective of this retrospective cohort study is to evaluate the incidence of TBI in patients with craniofacial trauma. Methods: The study included 2982 consecutive patients with either solitary or concurrent diagnoses of TBI and facial fractures, seen and evaluated at a single level II trauma center between January 1, 2010 and December 31, 2020. Continuous variables were compared against whether the patient had one or both diagnoses.Results: Of the target population, 55.8% had a solitary diagnosis of TBI, 30.28% had a solitary diagnosis of facial fractures, and 13.92% had concurrent diagnoses of both TBI and facial fractures. Patients with concurrent diagnoses had a significantly longer mean length of stay (LOS) compared to those with solitary diagnoses (9.92 ± 16.33 days vs. 6.21 ± 10.96 days, p<0.01), but age (p=0.68) and ICU LOS (p=0.09) did not differ significantly between the two groups. Conclusions: Trauma to the face should be given special attention due to the close relationship between facial bones and the brain. Patients with concurrent diagnoses of TBI and facial fractures had worse hospital outcomes than those with solitary diagnoses of either TBI or facial trauma.
CASE REPORT | doi:10.20944/preprints202306.0325.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Streptococcus intermedius; brain abscess; lung abscess; endocarditis
Online: 5 June 2023 (13:24:39 CEST)
Streptococcus intermedius is frequently associated with brain and liver abscesses, while pleuropulmonary infections are considered rarer. Even less frequent is the association of lung and brain abscess due to this agent with left heart endocarditis. We describe the case of a 40-year-old man with a brain abscess due to S. intermedius and concomitant lung abscess and aortic native valve endocarditis. He was treated with surgical drainage of the brain abscess and a 4-week course of intravenous ceftriaxone, followed by oral amoxicillin/clavulanate, obtaining healing of the lesions without relapse of the infection.
REVIEW | doi:10.20944/preprints202305.0429.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Ozone; Oxidative stress; Bowel; Brain; Degenerative disease
Online: 8 May 2023 (03:21:21 CEST)
Repeated exposure to environmental ozone causes a chronic state of oxidative stress. This state is present in chronic degenerative diseases and induces a loss of control of the inflammatory response. The dysfunction of redox system and failures in control the inflammatory responses are involved in a vicious circle that maintains and increases the degenerative process. Intestine also responds to secondary reactive species formed by exposure to ozone doses, generating noxious stimuli that increase degenerative damage. This review aims to elucidate how environmental pollution, mainly by ozone, induces a state of chronic oxidative stress with the loss of regulation of the inflammatory response, both in the intestine and in the brain, where the functionality of both structures is altered and plays a determining role in some neurodegenerative and chronic degenerative diseases. For this purpose, we searched for information on sites like the Cochrane Library Database, PubMed, Scopus, and Medscape. Reviewing the data published, we can conclude that environmental pollutants are a severe health problem. Ozone pollution has different pathways of action, both molecular and systemic, and participates in neurodegenerative diseases such as Parkinson's and Alzheimer's disease as well in bowel diseases as Inflammatory Bowel Disease, Crohn's Disease and Irritable Bowel Syndrome.
ARTICLE | doi:10.20944/preprints202302.0044.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Brain death diagnosis; Intracranial Pressure; Intracranial compliance
Online: 2 February 2023 (11:30:01 CET)
Background: Due to the importance of brain death (BD) diagnostic do not mistake, reliable confirmatory exams should be performed to enhance its security. This study aims to evaluate the intracranial pressure (ICP) pulse morphology behavior in brain-dead patients through a noninvasive monitoring system. Methods: A pilot case-control study was conducted in adults that met the BD national protocol criteria. Quantitative data from the ICP waveforms were extracted and analyzed comparing BD patients and health subjects. Results: Fifteen patients were included. ICP waveforms presented substantial differences amidst BD patients when compared to the control group. Moreover, pulse amplitude and time to peak variables values in the case group were also statistically significant. Conclusions: In this exploratory study, noninvasive ICP waveforms have shown potential as a screening method in patients with suspected brain death. Future studies should be carried out in a larger population.
CASE REPORT | doi:10.20944/preprints202302.0016.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: enfortumab vedotin; brain metastases; antibody-drug conjugate
Online: 1 February 2023 (16:46:24 CET)
Abstract: Enfortumab vedotin (EV), an antibody-drug conjugate directed against Nectin-4, signif-icantly prolonged survival when compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-based chemo-therapy and a PD-1 or PD-L1 inhibitor. The confirmed overall response rate in the phase 3 EV301 trial leading to approval was 40.6%. However, no data have been published about the activity in brain metastases. Here, we present three patients from different centers with brain metastases receiving EV. A 58-year-old male Caucasian patient, who was heavily pretreated for urothelial carcinoma with visceral metastases and a solitary clinically active brain metastasis, started on EV 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle. The first evaluation after three cycles of EV showed a partial remission by RECIST v1.1 with a near complete response in the brain metastasis and disappear-ance of the neurological complaints. The patient is currently still receiving EV. A second, 74-year-old male patient started on the same regimen, after previous progression on platinum-based chemotherapy and maintenance avelumab. The patient achieved complete response and remained on therapy for five months. However, therapy was discontinued at the patient’s re-quest. Shortly after, he developed new leptomeningeal metastases. Upon rechallenge with EV, there was a significant reduction in the diffuse meningeal infiltration. A third, 50-year-old male Caucasian patient also received EV, after previous progression on cisplatin-gemcitabine and ate-zolizumab maintenance followed by palliative whole brain radiotherapy and two cycles of vin-flunine. The first evaluation after three cycles of EV showed a significant reduction of the brain metastases. The patient is currently still receiving EV. These are the first reports on efficacy of EV in patients with urothelial carcinoma and active brain metastases.
REVIEW | doi:10.20944/preprints202211.0258.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: tardive dyskinesia; schizophrenia; antipsychotics; deep brain stimulation
Online: 14 November 2022 (11:12:39 CET)
Tardive dyskinesia (TD) is a phenomenon predominantly observed as a result of the long-term use of dopamine receptor blockers (antipsychotics). TD is a group of involuntary, irregular hyperkinetic movements, mainly in the muscles of the face, eyelid muscles, lips, tongue, and cheeks, and less frequently in the limbs, neck, pelvis, and trunk. In some patients, TD takes on an extremely severe form, massively disrupting functioning, moreover, causing stigmatization and suffering. Deep brain stimulation (DBS), a method used, among others, in Parkinson's disease, is also an effective treatment for TD and often becomes a method of last resort, especially in severe, drug-resistant forms. The procedure is relatively new in TD, so the available reliable clinical studies are few and consist mainly of case reports. Unilateral and bilateral stimulation of two sites has proven efficacy in TD treatment. Most authors describe stimulation of the globus pallidus internus (GPi); less frequent descriptions involve the hypothalamic nucleus (STN). In the present paper, we provide up-to-date information on the stimulation of both mentioned brain areas. We also compare the efficacy of the two methods by comparing the two available studies, which included the largest groups of patients. Although GPi stimulation is more frequently used clinically, our initial analysis indicates comparable results (reduction of involuntary movements) with STN DBS.
ARTICLE | doi:10.20944/preprints202210.0186.v3
Subject: Biology And Life Sciences, Biophysics Keywords: neural; brain; structural intelligence; cell expression; evolution
Online: 4 November 2022 (09:43:59 CET)
This concept paper gives a narrative about intelligence from insects to the human brain, showing where evolution may have been influenced by the structures in these simpler organisms. The ideas also come from the author's own cognitive model, where a number of algorithms have been developed over time and the precursor structures should be codable to some level. Through developing and trying to implement the design, ideas like separating the data from the function have become architecturally appropriate and there have been several opportunities to make the system more orthogonal. Similarly for the human brain, neural structures may work in-sync with the neural functions, or may be slightly separate from them. Each section discusses one of the neural assemblies with a potential functional result, that cover ideas such as timing or scheduling, structural intelligence and neural binding. Another aspect of self-representation or expression is interesting and may help the brain to realise higher-level functionality based on these lower-level processes.
ARTICLE | doi:10.20944/preprints202207.0229.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: Neurosciences; Artificial intelligence; brain modeling; Deep Learning
Online: 15 July 2022 (07:39:15 CEST)
If the development of machine learning and artificial intelligence plays a role in many fields of research and technology today, it has a special relationship with neurosciences. Indeed, historically inspired by our knowledge of the brain, deep learning shares some vocabularies with neurosciences and can sometimes be considered a brain’s model. Taking the particular example of epileptic seizure, which can develop in any biological neural tissue, we raise the question if and how the models used for deep learning can capture or model these pathological events. This particular example is a starting point to discuss the nature, limits, and functions of these models, and what we expect from a model of the brain. Finally, we argue that a pluralistic approach leading to the integrated coexistence of different models is necessary to study the brain in all its complexity.
REVIEW | doi:10.20944/preprints202207.0225.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: blood brain barrier; physiological; pathological; glioblastoma; intervention
Online: 14 July 2022 (15:02:52 CEST)
The blood brain barrier (BBB) is an essential component in regulating and maintaining the homeostatic microenvironment of the central nervous system (CNS). During the occurrence and development of glioblastoma (GBM), BBB is pathologically disrupted with markedly increased permeability. Due to the obstruction imposed by the BBB, strategies currently employed for GBM therapeutics still obtain a very low success rate and lead to systemic toxicity. Moreover, chemotherapy could promote pathological BBB functional restoration, accompanied with a prominent decrease of intracerebral therapeutics transportion during GBM multiple administration, resulting in chemotherapy failure for GBM treatment. The effective delivery of therapeutics into the brain still faces with severe challenges. Regulation of pathological BBB for enhanced transporting of therapeutics across the barrier may provide new opportunities for effective and safe treatment of GBM. This article reviews the structure and function of BBB in physiological state, the mechanisms underlying BBB pathological fenestration during the development of GBM, and the therapeutic strategies of GBM based on BBB intervention and therapeutic drugs transporting across the BBB.
BRIEF REPORT | doi:10.20944/preprints202202.0045.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: fNIRS; diabetes; brain imaging; point of care
Online: 3 February 2022 (10:10:08 CET)
Abstract—Low-frequency Fahræus–Lindqvist-driven (not blood pressure-driven) oscillations in the small vessels are crucial because oscillations in small vessels support nutrient supply. Understanding of this is critical in type 2 diabetes mellitus (T2DM) to develop therapeutic measures to prevent Alzheimer's Disease Related Dementias: vascular factors contribute to cerebrovascular disease as well as mild cognitive impairment and dementia, which are predicted to affect 152 million people by 2050 (Alzheimer's Disease International London, UK, 2019). In this clinical study, we performed functional near-infrared spectroscopy (fNIRS) of the forehead to investigate the effect of the Mini-Cog with three-item recall test on the prefrontal cortex (PFC) activation and the relative oscillatory power in the 0.01–0.02-Hz (Fahræus–Lindqvist effect) and 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency bands in elderly (60 years and older) T2DM and age-matched controls. We found a significant (p<0.01) difference in the PFC activation between elderly subjects with T2DM and age-matched elderly controls. Moreover, power spectral density (PSD) analysis revealed a significantly lower relative power in 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency band in elderly subjects with T2DM during the Mini-Cog three-item recall test. Furthermore, a drop in the oscillatory power in the 0.01–0.02-Hz frequency band during Mini-Cog three-item recall test was found more pronounced in the elderly subjects with T2DM. Therefore, our study highlighted portable brain imaging to capture cerebrovascular reactivity to cognitive load that may provide a biomarker of cerebrovascular dysfunction in T2DM.Clinical Relevance— Our study establishes forehead portable brain imaging for monitoring cerebrovascular function in T2DM under cognitive load.
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: G9a; EHMT2; glioblastoma; medulloblastoma; epigenetics; brain tumor
Online: 8 October 2021 (10:57:22 CEST)
Epigenetic mechanisms, including post-translational modifications of DNA and histones that influence chromatin structure, regulate gene expression during normal development, and are also involved in carcinogenesis and cancer progression. The histone methyltransferase G9a (euchromatic histone lysine methyltransferase 2, EHMT2), which mostly mediates mono- and dimethylation by histone H3 lysine 9 (H3K9), influences gene expression involved in embryonic development and tissue differentiation. Overexpression of G9a has been observed in several cancer types, and different classes of G9a inhibitors have been developed as potential anticancer agents. Here, we review the emerging evidence suggesting the involvement of changes in G9a activity in brain tumors, namely glioblastoma (GBM), the main type of primary malignant brain cancer in adults, and medulloblastoma (MB), the most common type of malignant brain cancer in children. We also discuss the role of G9a in neuroblastoma (NB) and the drug development of G9a inhibitors.
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Aged; Alanine Transaminase; Brain infarction; Frailty; Mortality
Online: 19 March 2021 (08:09:52 CET)
(1) Background: Extremely low alanine aminotransferase (ALT) levels are be-ing recognized as a risk factor of increasing mortality in the elderly in relation to frailty. In the elderly, both frailty and ischemic stroke are not only common, but also associated with mortality. This study aimed to investigate whether extremely low ALT levels increase the all-cause mortality rate in the elderly after ischemic stroke. (2) Methods: A retrospective review was performed on 901 patients with ischemic stroke admitted to a university-affiliated hospital between February 2014 and April 2019. The multivariate Cox proportional hazard analysis was performed to determine whether extremely low ALT lev-els are an independent risk factor of mortality in elderly patients after ischem-ic stroke. (3) Results: This study enrolled 323 older adults (age ≥65 years) who were first diagnosed with ischemic stroke. The mean age of the participants was 76.5 ± 6.6 years, mean survival time was 37.1 ± 20.4 months, and the num-ber of deaths was 96 (29.7%). The multivariate Cox proportional hazard analy-sis revealed that the risk factors for all-cause mortality in the elderly after is-chemic stroke were age, initial National Institutes of Health Stroke Scale score, serum creatinine, and extremely low ALT level (<10 U/L) at the time of diag-nosis (adjusted hazard ratio: 3.243, 95% confidence interval: 1.945–5.408; P < 0.001) (4) Conclusions: Extremely low ALT level at the time of diagnosis (<10 U/L) is an independent risk factor that increases the mortality rate in the el-derly after ischemic stroke.
ARTICLE | doi:10.20944/preprints202103.0136.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Sleep apnea; hypoxemia; cognitive; brain health; MRI
Online: 3 March 2021 (14:14:41 CET)
We aim to determine the sleep correlates of age-related brain loss in a sample of middle-aged to older males with obstructive sleep apnea. We evaluated consecutive treatment naïve male patients with OSA (AHI≥15 events/hr) without dementia, stroke or heart disease, from January to November of 2019. We collected demographic variables, vascular risk factors, and sleep questionnaires. We also obtained computerized neurocognitive testing with the Go-No-Go Response Inhibition Test, Stroop Interference Test, Catch Game Test, Staged Information Processing Speed Test, Verbal Memory Test and Non-Verbal Memory Test. We derived age and education adjusted domain-specific Z-scores for global cognition, memory, attention, processing speed and executive function. We used brain MRI T1-weighted images to derive total hippocampal and gray matter volumes. Partial correlations evaluated associations between the ISI, AHI, and oxygen level during sleep, with cognitive domains and brain volumes. Sixteen participants, age 40-76 years, 73% Hispanic/Latino, with mean AHI=48.9±25.5 and mean oxygen saturation of 91.4±6.9% during sleep. Hypertension was seen in 66% and diabetes in 27%. We observed that ISI and oxygen level during sleep had strong correlations with brain volumes and cognition. These preliminary findings may aid in developing future strategies to improve age-related brain loss in OSA.
REVIEW | doi:10.20944/preprints202009.0539.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: brain aging; energy metabolism; neurodegeneration; neurodegenerative disorders
Online: 23 September 2020 (04:55:21 CEST)
A growing body of evidence indicates that aging of the brain is strictly related to the decline of energy metabolism. In particular, in older adults, the neuronal metabolism of glucose declines steadily resulting in a growing deficit of ATP production. The decline is evoked by deficient NAD recovery in the salvage pathway and subsequent impairment of the Krebs cycle. NAD deficit impairs also the activity of NAD-dependent enzymes. All these open vicious circles of neurodegeneration and neuronal death. Some brain structures are particularly prone to aging and neurodegeneration. These are pathological foci of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. This review article summarizes the impacts and mutual relationships between metabolic processes both on neuronal and brain levels. It also provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.
REVIEW | doi:10.20944/preprints202008.0658.v1
Subject: Biology And Life Sciences, Virology Keywords: glioma; oncolytic virus; glioblastoma; virotherapy; brain tumor
Online: 30 August 2020 (11:17:24 CEST)
Glioma tumors are one of the most devastating cancer types. Of the different glioma tumors, glioblastoma is the most advanced stage with the worst prognosis. Current therapies are still unable to provide an effective cure. Recent advantages in oncolytic immunotherapy have generated great expectations in the cancer therapy field. The use of oncolytic viruses (OV) in cancer treatment is one of those immune-therapeutic alternatives. OV have a double oncolytic action by both, directly destroying the cancer cells, sparing the patient’s life, and stimulating a tumor specific immune response to revert the ability of tumors to escape the control of the immune system. OV are one promising alternative to conventional therapies in glioma tumor treatment. Several clinical trials have proven the feasibility to use some viruses to specifically infect tumors eluding undesired toxic effects in the patient. Here we have revisited the literature in order to describe the main OV proposed so far as therapeutic alternatives to destroy glioma cells in vitro and trigger tumor destruction in vivo. Some clinical trials are exploring the use of this therapy as an alternative were other approaches provide limited hope.
SHORT NOTE | doi:10.20944/preprints202003.0014.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: brain death; determination of death; neurological criteria
Online: 1 March 2020 (13:28:26 CET)
Lewis et al. published an important and timely necessary article about the determination of death by neurological criteria, revising the Uniform Determination of Death.The acceptance of brain death (BD) has been progressively accepted beginning at the late 1950s. Nonetheless, contentious brain-death cases have recently raised new controversies about the diagnosis of BD, such as the Jahi McMath case, extensively covered by the US and international press. Jahi McMath meant a terrible tragedy for her and her family. But further than this gloomy story, the case has also raised confusion and challenging qualms about a fundamental query: how we confirm whether a person is dead or alive? Since 1981, the Uniform Determination of Death Act (UDDA) has served as the legal foundation for the medical practice of determining death. But, although death by neurologic criteria is considered legal death throughout the United States, several recent lawsuits have quizzed the rightfulness the authority of the UDDA to declare death by neurological criteria. This issue explains the importance of Lewis’s et al. paper. In this article I want to present the historical procedure for issuing a law in Cuba for the determination and certification of death. Of course, it is impossible to compare our country with USA. Cuba is a small and developing country, in which a law encompasses a national scenery, in contrast with USA, a multistate nation.
Subject: Biology And Life Sciences, Biophysics Keywords: brain; nervous system; Einstein; relativity; spacetime; mind
Online: 22 November 2019 (06:46:57 CET)
Visual imagery, i.e., the mental experience of an object occurring in the absence of external visual stimulus, might encompass diverse content according to different observers. Further, subjectively experienced time is encoded in the later entorhinal cortex. Starting from these two observations, and considering Einstein’s account of spacetime, we show how, in terms of special relativity, the content of visual imagery is not stationary and fixed, rather depends on the standpoint of the observer. We elucidate how the subjective definition of time (perceived by our mind as static) might give rise to modifications in the length of the imagined object which are experimentally assessable and quantifiable. In particular, based on recent neuroscientific literature, we show how changes in our mental time windows are able to squeeze the visual content of mental imagery.
REVIEW | doi:10.20944/preprints201810.0554.v1
Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: gut brain axis; microbiota; functional gastrointestinal disorders
Online: 24 October 2018 (07:41:58 CEST)
The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine and immunological mechanisms. The scientific data are mounting that gut microbiota is a source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in control of emotions, physical activity and cognition. Most of GI maladies are associated with altered transmission within the GBA and influenced both by genetic and environmental factors. Current treatment protocols widely advocated for the treatment of GI disorders may positively or adversely affect the composition of intestinal microbiota with diverse impact on therapeutic outcome. The alterations of gut microbiota have been associated with mood and depressive disorders. and mental health is frequently altered in the course of many GI and non-GI ailments. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Psychobiotics are new class of beneficial bacteria, with documented efficacy in the treatment of gut-brain axis disorders.
ARTICLE | doi:10.20944/preprints201612.0060.v1
Subject: Computer Science And Mathematics, Software Keywords: neonatal MRI; brain structure segmentation; volume extraction
Online: 10 December 2016 (08:44:55 CET)
1) Introduction: Brain parcellation is an important processing step in the analysis of structural brain MRI. Existing software implementations are optimized for fully developed adult brains, and provide inadequate results when applied to neonatal brain imaging. 2) Methods: We developed a semi-automated pipeline, NeBSS, for extracting 50 discrete brain structures from neonatal brain MRI, using an atlas registration method that leverages the existing ALBERT neonatal atlas 3) Results: We demonstrate a simple linear workflow for neonatal brain parcellation. NeBSS is robust to variation in imaging acquisition protocol and magnet field strength. 4) Conclusion: NeBSS is a robust pipeline capable of parcellating neonatal brain MRIs using a simple processing workflow. NeBSS fills a need in clinical translational research in neonatal imaging, where existing automated or semi-automated implementations are too rigid to be successfully applied to multi-center neuroprotection studies and clinically heterogeneous cohorts. The software is open source and freely available.
ARTICLE | doi:10.20944/preprints202307.0938.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: major depressive disorder; bipolar disorder; infectious diseases; upper respiratory infections; lower respiratory infections; lung-brain axis; gut-brain axis
Online: 13 July 2023 (12:23:28 CEST)
Mood disorders are among the commonest mental disorders worldwide. Epidemiological and clinical evidence suggests that there are close links between infectious diseases and mood disorders, but the strength and direction of these association remain largely unknown. Theoretical models have attempted to explain this link based on evolutionary or immune-related factors, but these have not been empirically verified. The current study examined cross-sectional and longitudinal associations between the incidence of infectious diseases and mood disorders, while correcting for climate and economic factors, based on data from the Global Burden of Disease Studies, 1990-2019. It was found that major depressive disorder was positively associated with lower respiratory infections, while bipolar disorder was positively associated with upper respiratory infections and negatively associated with enteric and tropical infections, both cross-sectionally and over a period of thirty years. These results suggest that a complex, bidirectional relationship exists between these disorders. This relationship may be mediated through the immune system as well as through the gut-brain and lung-brain axes. Understanding the mechanisms that link these groups of disorders could lead to advances in the prevention and treatment of both.
REVIEW | doi:10.20944/preprints202311.1857.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: vision; hearing; tasting; smelling; head; face; brain stem
Online: 29 November 2023 (06:18:33 CET)
The twelve cranial nerves play a crucial role in nervous system, orchestrating a myriad of functions vital for our everyday life. These nerves are each specialized for particular tasks. Cranial Nerve I, known as the olfactory nerve, is responsible for our sense of smell, allowing us to perceive and distinguish various scents. Cranial Nerve II, or the optic nerve, is dedicated to vision, transmitting visual information from the eyes to the brain. Eye movements are governed by Cranial Nerves III, IV, and VI, ensuring our ability to track objects and focus. Cranial Nerve V controls facial sensation and jaw movement, while Cranial Nerve VII, the facial nerve, facilitates facial expressions and taste perception. Cranial Nerve VIII, or the vestibulocochlear nerve, plays a critical role in hearing and balance. Cranial Nerve IX, the glossopharyngeal nerve, affects throat sensation and taste perception. Cranial Nerve X, the vagus nerve, is a far-reaching nerve, influencing numerous internal organs such as the heart, lungs, and digestive system. Cranial Nerve XI, the accessory nerve, is responsible for neck muscle control, contributing to head movement. Finally, Cranial Nerve XII, the hypoglossal nerve, manages tongue movement, essential for speaking, swallowing, and breathing. Understanding these cranial nerves is fundamental in comprehending the intricate workings of our nervous system and the functions that sustain our daily lives.
ARTICLE | doi:10.20944/preprints202311.1273.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: Resonance; Brain; Consciousness; Criticality; Biofield; Continuum Theory; Entrainment
Online: 21 November 2023 (05:58:39 CET)
Abstract: Aim: Biofields combine many physiological levels both spatially and temporally. These biofields reflect naturally resonant forms of synaptic energy reflected in growing and spreading waves of brain activity. The study desires to theoretically understand better how resonant continuum waves may be reflective of consciousness, memory, and thought. Background: The metabolic processes that maintain animal cellular and physiological function are enhanced by physiological coherence. Internal biological system coordination and sensitivity to particular stimuli and signal frequencies are two aspects of coherent physiology. There exists significant support for the notion that exogenous biologically and non-biologically generated energy entrains human physiological systems. All living things have resonant frequencies that are either comparable or coherent, therefore eventually all species will have a shared resonance. An organism's biofield activity and resonance are what support its life and allow it to react to stimuli. Methods: As the naturally resonant forms of synaptic energy are growing and spreading waves of brain activity, The temporal and spatial frequency of waves are effectively regulated by a time delay (T) in inter-layer signals in a layered structure that mimics the structure of the mammalian cortex. From ubiquitous noise, two different types of waves can arise as a function of T. One is coherent, and as T rises, so does its resonant spatial frequency. Results: Continued growth eventually causes both the wavelength and the temporal frequency to abruptly increase. Two waves expand simultaneously and randomly interfere in an area of T values as a result. Conclusion: We suggest that because of this extraordinary dualism, which has its roots in the phase relationships of amplified waves, coherent waves are essential for memory retrieval whereas random waves represent original cognition.
ARTICLE | doi:10.20944/preprints202310.0378.v2
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Tubulin; microtubules; immune system; brain; consciousness; Orch OR
Online: 16 November 2023 (10:01:39 CET)
This study describes the design and development of novel compounds aimed at optimizing the function of microtubules and tubulin in the immune system and the brain as they relate to the Orch OR theory of consciousness. These compounds are defined by the following molecular formulas:C65H100CoN15O22P(C6H12O5);C65H100CoN15O22P(C5H10NO4);(C65H100CoN15O22P)(C6H12N2O)n;(C65H100CoN15O22P)(C6H12O5)(C6H12N2O)n;(C6H12N2O)n(C6H12O5)m;Zn(C6H12O5)2;These molecules, formulated under the form of drugs, health functional foods, or food supplements, have the potential to positively affect a number of areas ranging from prevention and therapy of neurological diseases to supporting the immune system.
ARTICLE | doi:10.20944/preprints202309.1626.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: alcohol; brain networks; adolescents; resting-state connectivity; fMRI
Online: 25 September 2023 (05:20:04 CEST)
Approximately 6 million youth aged 12 to 20 consume alcohol monthly in the United States. The effect of alcohol consumption in adolescence on behavior and cognition is heavily researched, however, little is known about how alcohol consumption in adolescence may alter brain function, leading to long-term developmental detriments. In order to investigate differences in brain connectivity associated with alcohol use in adolescents, brain networks were constructed using resting state functional magnetic resonance imaging data collected by the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) from 698 youth (12-21 years, 117 hazardous drinkers and 581 no/low drinkers). Analyses assessed differences in brain network topology based on alcohol consumption in eight pre-defined brain networks, as well as in whole-brain connectivity. Within the central executive network (CEN), basal ganglia network (BGN), and sensorimotor network (SMN), no/low drinkers demonstrated stronger and more frequent connections between highly globally efficient nodes, with fewer and weaker connections between highly clustered nodes. Inverse results were observed within the dorsal attention network (DAN), visual network (VN), and frontotemporal network (FTN), with no/low drinkers demonstrating weaker connections between nodes with high efficiency and increased frequency of clustered nodes compared to hazardous drinkers. Results from this study show clear organizational differences between adolescents with no/low or hazardous alcohol use, suggesting that aberrant connectivity in these brain networks is associated with risky drinking behaviors.