Mind and brain/matter interaction is one of the important and controversial issues in Islamic philosophy. In fact, in the resources of Islamic philosophy, one of the basic parts of philosophical discussions is related to mind’s nature and its interaction with the brain. Especially, in Avicenna’s philosophy, there are many articles and books which have addressed the topic of mind and brain and the relation between them. Avicenna was a profound philosopher, an expert physicist and a proficient physician of his time. Because of his experimental proficiency in medicine and surgery and his deep philosophical analysis, his discussion about mind and brain is very interesting for our time, due to recent advances in neuroscience. In this article, we have explained one of Avicenna’s arguments (in his famous opus “al-Isharat”) about the incorporeity of mind (self), which is very close to modern neuroscience and physics literature. In addition, we explain his model of mind and brain interaction. Avicenna described the mechanism of the causal effect of mind on the brain via a third identity, which works as an interface between them (in his main book “al-Shifa”). We try to illustrate his model by the use of some examples, inspired from modern physics. Also, we explore the philosophical constraints which must be considered in any model of mind-matter interaction, within the Islamic philosophy framework. In fact, we propose a new understanding of Avicenna’s philosophy which is in agreement with modern physics and neuroscience.

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.

Studies in animal models have suggested that the ketogenic diet may be effective in the treatment of cancer. However, human cohort studies on the ketogenic diet have, thus far, failed to show benefits in cancer survival or in any other hard clinical endpoints of the disease. This paper presents a case report of a patient with glioblastoma multiforme. The patient had initially been treated with standard oncotherapy including surgery, radiotherapy and chemotherapy. Despite standard treatment, the patient experienced a recurrence of the glioblastoma seven months later. Subsequently, the patient refused radiotherapy and chemotherapy and opted to use the paleolithic ketogenic diet (PKD) as a stand-alone therapy. Following the adoption of the PKD, progression of the disease has been completely halted. At the time of writing, the patient has remained in remission for 48 months, is without side-effects and experiences an excellent quality of life without the use of any drugs.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

In the field of nasal delivery, one of the most fascinating applications is the delivery of drugs directly to the central nervous system bypassing the blood brain barrier. This approach would provide a series of benefits, such as dose lowering and direct targeting of potent drugs, ultimately reducing their systemic side effects. Recently, clinical trials have explored the nasal administration of insulin for the treatment of Alzheimer’s disease, with promising results. The use of nanomedicines could provide further options for making nose-to-brain delivery reality. In particular, apart from the selection of devices able to deposit the formulation in the upper part of the nose, surface modification of these nanomedicines appears the key strategy to optimize the delivery of drugs from the nasal cavity to the brain. In this review, nanomedicines delivery approaches based on surface electrostatic charges, mucoadhesive polymers, as well as chemical moieties targeting nasal epithelium, will be discussed and critically evaluated for nose-to-brain delivery.

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.

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.

Metabolomic analysis of biological fluids and tissues has become an increasingly routine tool in the biological toolbox. However, challenges remain to be overcome, including developing strategies to maximise coverage of the metabolome without requiring large sample volumes. Here we describe a multimodal strategy that combines data using both LC-MS and GC-MS from a unique vial with a sample of plasma (20µl) or a sample of brain tissue (3mg). Using a split phase extraction the non-aqueous phase was analyzed by reversed phase (RP) LC-MS, whilst the aqueous phase was analyzed using hydrophilic liquid interaction chromatography (HILIC)LC-MS, with both phases also analysed using GC-MS after derivatization of the extract. Analytical performance was assessed in 7 rat cerebellum samples and a pilot study of 40 plasma samples (20 vs. 20: AD vs. healthy controls). The method, which uses four hours of instrument time, measured 20,707 metabolite features in brain samples and 17,266 in plasma samples, from those 44.1% features displayed CV’s below 15% and 75.2% below 30%. The method has potential to resolve subtle biological differences and to correlate metabolite composition directly to clinical outcomes including MMSE, age and ADCS-ADL. This method can acquire in the order of 20K metabolic features when low volumes are available.

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.

Currently there is little doubt left on the symbiogenetic nature of eukaryotes - genomes of archaeon and bacterium participated in shaping a genome of last eukaryotic common ancestor in equal albeit asymmetric manner, while a merger event itself indicated the advent of a new domain of life. The “symbiogenetic” framework of interaction of two partners is proposed, outlining similar steps essential for three major advents: the origin of life, the origin of complex life and the origin of humans. Given the immense importance of proper energy source for the evolution of life it seems plausible that for any principal increase in complexity, a partnership with a novel energy donor is required. Moreover, a “language” elaborated in the course of communication of partners might have been a prerequisite for a subsequent increase in complexity. Transitions, which led to RNA-protein world, eukaryotes and human brain, resulted in advent of complex languages via communication onsets between two entities in close partnership. Accordingly this further facilitated formation of first cells, multicellular organisms and human society.

Brain metastases are highly evolved manifestations of breast cancer arising in a unique microenvironment, giving them exceptional adaptability in the face of new extrinsic pressures. The incidence is rising in line with population ageing, and use of newer therapies that stabilise metastatic disease burden with variable efficacy throughout the body. Historically, there has been a widely held view that brain metastases do not respond to circulating therapeutics because the blood-brain-barrier (BBB) restricts their uptake. However, emerging data are beginning to paint a far more complex picture where the brain acts as a sanctuary for dormant, subclinical proliferations that are initially protected by the BBB, but then exposed to dynamic selection pressures as tumours mature and vascular permeability increases. Here, we review key experimental approaches and landmark studies that have charted the genomic landscape of breast cancer brain metastases. These findings are contextualised with the factors impacting on clonal outgrowth in the brain: intrinsic breast tumour cell capabilities required for brain metastatic fitness, and the neural niche, which is initially hostile to invading cells but then engineered into a tumour-support vehicle by the successful minority. We also discuss how late detection, abnormal vascular perfusion and interstitial fluid dynamics underpin the recalcitrant clinical behaviour of brain metastases, and outline active clinical trials in the context of precision management.

Neuroscience has overwhelmingly and understandably focused on the synaptic modality of signal transmission. There is evidence, however, that from an evolutionary perspective, non-synaptic transmission (NST) preceded synaptic signaling. Moreover, in modern nervous systems, NST coexists and extensively interacts with synaptic transmission modifying neuronal dynamics. In fact, NST remains widespread in complex animals, especially within the interoceptive system where the dearth of insulating barriers such as myelin sheaths and the blood-brain barrier enhances the communication between neural and non-neural tissues mediated by NST. We suggest that this physiological arrangement makes a fundamental contribution to interoception¾the process of sensing visceral states¾which is an essential underpinning of the capacity to feel and the foundation of affective processing.

Non-invasive, electroencephalography (EEG)-based brain-computer interfaces (BCIs) on motor imagery movements translate the subject’s motor intention into control signals through classifying the EEG patterns caused by different imagination tasks, e.g. hand movements. This type of BCI has been widely studied and used as an alternative mode of communication and environmental control for disabled patients, such as those suffering from a brainstem stroke or a spinal cord injury (SCI). Notwithstanding the success of traditional machine learning methods in classifying EEG signals, these methods still rely on hand-crafted features. The extraction of such features is a difficult task due to the high non-stationarity of EEG signals, which is a major cause for the stagnating progress in classification performance. Remarkable advances in deep learning methods allow end-to-end learning without any feature engineering, which could benefit BCI motor imagery applications. We developed three deep learning models: 1) a long short-term memory (LSTM); 2) a proposed spectrogram-based convolutional neural network model (pCNN); and 3) a recurrent convolutional neural network (RCNN), for decoding motor imagery movements directly from raw EEG signals without (manual) feature engineering. Results were evaluated on our own, publicly available, EEG data collected from 20 subjects and on an existing dataset known as 2b EEG dataset from "BCI Competition IV". Overall, better classification performance was achieved with deep learning models compared to state-of-the art machine learning techniques, which could chart a route ahead for developing new robust techniques for EEG signal decoding. We underpin this point by demonstrating the successful real-time control of a robotic arm using our CNN based BCI.

Modularity is arguably one of the most influential theses guiding research on brain and cognitive function since phrenology. This paper considers the following question: is modularity entailed by recent Bayesian models of brain and cognitive function, especially the predictive processing framework? It starts by considering three of the most well-articulated arguments for the view that modularity and predictive processing work well together. It argues that all three kinds of arguments for modularity come up short, albeit for different reasons. The analysis in this paper, although formulated in the context of predictive processing, speaks to broader issues with how to understand the relationship between functional segregation and integration and the reciprocal architecture of the predictive brain. These conclusions have implications for how to study brain and cognitive function. Specifically, when cognitive neuroscience works within an acyclic Markov decision scheme, adopted by most Bayesian models of brain and cognitive function, it may very well be methodologically misguided. This speaks to an increasing tendency within the cognitive neurosciences to emphasise recurrent and reciprocal neuronal processing captured within newly emerging dynamical causal modelling frameworks. The conclusions also suggest that functional integration is an organising principle of brain and cognitive function.

The purpose of the present study was to investigate the effects of psychological pressure on corticospinal excitability, the spinal reflex, lower limb muscular activity, and reaction times during a task involving dominant leg movements. Ten healthy participants performed a simple reaction time task by raising the heel of their dominant foot from a switch. After 20 practice trials, participants performed 20 non-pressure and 20 pressure trials in a counterbalanced order. Stress responses were successfully induced, as indexed by significant increases in state anxiety, mental effort, and heart rates under pressure. Significant increases in motor evoked potential (MEP) amplitude of the tibialis anterior muscle (TA) occurred under pressure. In terms of task-related EMG amplitude, the co-contraction rate between the soleus (SOL) and TA muscles significantly increased along with SOL and TA EMG amplitudes under pressure. Hoffmann reflexes for SOL and reaction times did not change under pressure. These results indicate that corticospinal excitability and leg muscle-related EMG activity increase homogeneously during lower limb movements that are performed under psychological pressure.

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.

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). TNF-a or IL-17 stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express VCAM-1, the receptor responsible for inflammatory cell adhesion, which binds VLA-4 on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-a and IL-17 on the adherence of Th17 cells to bEnd.3 The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This interaction between Th17 cells and the brain endothelium appears to be mediated by VCAM-1 and some chemotactic cytokines. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.

This paper proposes several LabVIEW applications to accomplish the data acquisition, processing, features extraction and real-time classification of the electroencephalographic (EEG) signal detected by the embedded sensor of the NeuroSky Mindwave Mobile headset. The LabVIEW applications are aimed at the implementation of a Brain-Computer Interface system, which is necessary to people with neuromotor disabilities. It is analyzed a novel approach regarding the preparation and automatic generation of the EEG dataset by identifying the most relevant multiple mixtures between selected EEG rhythms (both time and frequency domains of raw signal, delta, theta, alpha, beta, gamma) and extracted statistical features (mean, median, standard deviation, route mean square, Kurtosis coefficient and others). The acquired raw EEG signal is processed and segmented into temporal sequences corresponding to the detection of the multiple voluntary eye-blinks EEG patterns. The main LabVIEW application accomplished the optimal real-time artificial neural networks techniques for the classification of the EEG temporal sequences corresponding to the four states: 0 - No Eye-Blink Detected; 1 - One Eye-Blink Detected; 2 – Two Eye-Blinks Detected and 3 – Three Eye-Blinks Detected. Nevertheless, the application can be used to classify other EEG patterns corresponding to different cognitive tasks, since the whole functionality and working principle could estimate the labels associated with various classes.

Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood–brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, new rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the most innovative approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proved to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review revels an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

Blood-brain-barrier is a major obstacle in treating brain-related disorders as it does not allow to deliver drugs in the brain. In order to facilitate delivery of drugs in brain, we developed a method for predicting blood-brain-barrier penetrating peptides. These blood-brain barriers penetrating peptides (B3PPs) can act as therapeutic as well as drug delivery agents. We trained, tested, and evaluated our models on blood-brain-barrier peptides obtained from the B3Pdb database. First, we compute a wide range of peptide features then we select relevant peptide features. Finally, we developed numerous machine learning-based models for predicting blood-brain-barrier peptides using selected features. Our model based on random forest performed best on the top 80 selected features and achieved a maximum 85.08% accuracy with 0.93 AUROC. We also developed a web server, B3pred that implements our best models. It has three major modules that allow users to; i) predict B3PPs, ii) scanning B3PPs in a protein sequence, and iii) designing B3PPs using analogs. Our web server and standalone software is freely available at https://webs.iiitd.edu.in/raghava/b3pred/.

The prevalence of obesity and eating disorders varies by sex, but the extent to which sex influences eating behaviors, especially in childhood, has received less attention. The purpose of this paper is to review the literature on sex differences in eating behavior in children and present new findings supporting the role of sex in child appetitive traits and neural responses to food cues. In children, the literature shows sex differences in basic taste response, food acceptance, eating self-regulation, and appetitive traits. New analyses demonstrate that sex interacts with child weight status to differentially influence appetitive traits and neural responses to food cues. Further, neuroimaging results suggest that obesity in female children is positively related to brain reactivity to higher-energy-dense food cues in regions involved with learning, memory, and object recognition, while the opposite was found in males. In addition to differences in how the brain processes information about food, other factors that may contribute to sex differences include parental feeding practices, societal emphasis on dieting, and peer influences. Future studies are needed to confirm these findings, as they may have implications for the development of effective intervention programs to improve dietary behaviors and prevent obesity.

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.

Interferon regulatory factor 5 (IRF5) is known to be involved in the innate immune response and pro-inflammatory cytokines. However, the roles of IRF5 in immune responses in Malabar grouper (Epinephelus malabaricus) have not been extensively explored. In this study, IRF5 gene was identified and characterized from M. grouper. The full-length IRF5 cDNA consisted of a 5’ terminal untranslated region (5’-UTR) of 289 bp and a 3’-UTR of 542 bp, an open reading frame (ORF) of 1500 bp encoding a polypeptide of 499 amino acids with a predicted molecular mass of 56.28 kDa and isoelectric point (pI) of 5.2. The putative MgIRF5 protein consists of four important conserved domains: a helix DNA-binding domain (DBD) at the N-terminus, a middle region, an IRF association domain (IAD) and a virus activated domain (VAD) at the C-terminus. Sequence alignment and phylogenetic analysis showed that highest sequence similarity of IRF5 was observed between the IRF5 genes from Oplegnathus fasciatus and Miichthys miiuy. The mRNA transcripts of IRF5 were detected in a wide range of tissues types from healthy M. grouper with highest expression in muscle, liver and skin. After treatment with poly (I: C), it was significantly up-regulated in spleen and liver tissues. When infected with NNV, the expression level of MgIRF5 was up-regulated in spleen and head kidney and their transcriptional responses to IRF5 increased in the grouper kidney cells. This approach suggests that MgIRF5 is important in the underlying mechanism of the innate immune responses against antiviral response.

Corticospinal excitability and particularly the balance between cortical inhibitory and excitatory processes (assessed in a muscle using transcranial magnetic stimulation), are affected by neurodegenerative pathologies or following a stroke. Non-fatiguing conventional locomotor exercise, such as cycling or walking, decreases intracortical inhibition and/or increases intracortical facilitation. These modifications notably seem to be a consequence of neurotrophic factors (e.g., brain-derived neurotrophic factors) resulting from hemodynamic solicitation. Furthermore, it can be inferred from non-invasive brain and peripheral stimulation studies that repeated activation of neural networks can endogenously shape neuroplasticity. Such mechanisms could also occur following eccentric exercises (i.e., active lengthening of the muscle), during which motor-related cortical potential is of greater magnitude and lasts longer (assessed by electroencephalography) than during concentric exercises (i.e., muscle shortening). As single-joint eccentric exercise decreased short- and long-interval intracortical inhibition and increased intracortical facilitation (assessed by paired-pulse transcranial magnetic stimulation immediately after), locomotor eccentric exercise may be even more potent by adding hemodynamic-related neuroplastic processes to endogenous processes. Besides, eccentric exercise is especially useful to develop relatively high force levels at low cardiorespiratory and perceived intensity, which can be a training goal in addition to inducing neuroplastic changes. Further studies are required to understand how neuroplasticity is 1) acutely influenced by locomotor exercise characteristics (e.g., intensity, duration), 2) modulated by an exercise-based rehabilitation program, 3) related to functional cognitive and motor outcomes relevant to pathological population.

Background: Post-traumatic stress disorder (PTSD) is a common debilitating psychiatric condition for which pharmacological therapy is not always solvable. Various treatments have been suggested for these patients. Deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD. 2) Methods: We review the neurocircuitry and up to date clinical concepts that may be of relevance for the implementation of DBS in posttraumatic stress disorder (PTSD). 3) Results: The role of DBS in treatment-refractory PTSD patients has been investigated relying on both preclinical and clinical studies. 4) Conclusions: DBS for PTSD is in its preliminary phases and likely to provide hope to patients with medical refractory PTSD following the results of randomized controlled studies.

Multidisciplinary neurotechnology holds the promise of understanding and non-invasively treating neurodegenerative diseases. In this preclinical trial on Parkinson's disease (PD), we combined neuroscience together with the nascent field of medical virtual reality and generated several important observations. First, we established the Oculus Rift virtual reality system as a potent measurement device for parkinsonian involuntary hand tremors (IHT). Interestingly, we determined changes in rotation were the most sensitive marker of PD IHT. Secondly, we determined parkinsonian tremors can be abolished in VR with algorithms that remove tremors from patients' digital hands. We also found that PD patients were interested in and were readily able to use VR hardware and software. Together these data suggest PD patients can enter VR and be asymptotic of PD IHT. Importantly, VR is an open-medium where patients can perform actions, activities, and functions that positively impact their real lives - for instance, one can sign tax return documents in VR and have them printed on real paper or directly e-sign via internet to government tax agencies. Lastly, we generated a technical framework wherein movements in the real world can be measured side-by-side with those in virtual reality. With this framework, we observed anecdotal evidence of parkinsonian tremors being reduced in real life when our algorithms abolished digital hand tremors in VR.

Without protective and/or therapeutic agents the SARS-CoV-2 infection known as coronavirus disease 2019 (COVID-19) is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS-CoV-2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS-CoV-2 components could use to reach the CNS and PNS, utilizing the within-body crosstalk between organs. The majority of SARS-CoV-2 infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune-mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood-endothelial-barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

Based on the geologic conditions of natural gas hydrate (NGH) accumulations in the Shenhu area, northern slope of the South China Sea, this paper used a method of combining reservoir stimulation technique (RST) with depressurization to investigate the conversion efficiency of marine NGH reservoirs in different intrinsic permeability and initial NGH saturation conditions, and analyze the influence of variably-stimulation effect on marine NGH conversion efficiency in different accumulation conditions, provided a reference scheme for improving the NGH conversion efficiency in the Shenhu area. In this work, we performed calculations for the variations in CH4 production rate and cumulative volume of CH4 in different initial NGH saturation, intrinsic permeability and stimulation effect conditions, variance analysis and range analysis methods were used to analyze the significance of these key factors and their interaction, and investigated the sensitivity of stimulation effect on NGH conversion efficiency, respectively. The simulation results showed that stimulation effect have a significant influence on NGH conversion efficiency, and the influence of interaction between these three factors were not obvious. Possibly most important, we clarified an optimum stimulation effect for higher NGH conversion efficiency under different accumulation conditions, especially in low-permeability and high-saturation, which corresponding stimulation effect were different.

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.

Neural microprobes represent an important component of neural prosthetic systems where implanted microprobes record the electro-potentials generated by specific thoughts in the brain and convey the signals to algorithms trained to interpret these thoughts. Here, we present novel elongated multi-site neural probe that can reach depths greater than 10mm. We hypothesize that reaching such depth allows the recording of cognitive signals required to drive cognitive prosthetics. The impedance of the recording sites on the probes was on the order of 500 kΩ at 1 kHz, which is consistent with probes used for neurophysiological recordings. The probes were made porous using Xenon Difluoride (XeF₂) dry etching to improve the biocompatibility and their adherence to the surrounding neural tissue. Numerical studies were performed to determine the reliability of the porous probes. We implanted the elongated probe in rats and show that the elongated probes are capable of simultaneously recording both spikes and local field potentials (LFPs) from various recording sites.

Social plasticity, defined as the ability to adaptively change the expression of social behavior according to previous experience and to social context, is a key ecological performance trait that should be viewed as crucial for Darwinian fitness. The neural mechanisms for social plasticity are poorly understood, in part due to skewed reliance on rodent models. Fish model organisms are relevant in the field of social plasticity for at least two reasons: first, the diversity of social organization among fish species is staggering, increasing the breadth of evolutionary relevant questions that can be asked. Second, that diversity also suggests translational relevance, since it is more likely that “core” mechanisms of social plasticity are discovered by analyzing a wider variety of social arrangements than relying on a single species. We analyze examples of social plasticity across fish species with different social organizations, concluding that a “core” mechanism is the initiation of behavioral shifts through the modulation of a conserved “social decision-making network”, along with other relevant brain regions, by monoamines, neuropeptides, and steroid hormones. The consolidation of these shifts may be mediated via neurogenomic adjustments and regulation of the expression of plasticity-related molecules (transcription factors, cell cycle regulators, and plasticity products).

In the last years evidence has emerged that neurodegenerative diseases (NDs) are strongly associated with the microbiome composition in the gut. Parkinson’s disease (PD) is the most intensively studied neurodegenerative disease in this context. In this review, we performed a systematic evaluation of published literature comparing changes in colonic microbiome in PD to the ones observed in other NDs including Alzheimer’s Disease (AD), Multiple system atrophy (MSA), Multiple sclerosis (MS), Neuromyelitis optica (NMO) and Amyotrophic lateral sclerosis (ALS). To warrant comparability of different studies, only human case-control studies were included. Several studies showed an increase of Lactobacillus, Bifidobacterium, Verrucomicrobiaceae and Akkermansia in PD. A decrease in PD was observed of Faecalibacterium spp., Coprococcus spp., Blautia spp., Prevotella spp. and Prevotellaceae. On low taxonomic resolution, like phylum level, the changes are not disease specific and inconsistent. However, on higher taxonomic resolution like genus or species level, a minor overlap was observed between PD and MSA, both alpha synucleinopathies. We show that a methodical standardization of sample collection and analysis is necessary for ensuring the reproducibility and comparability of data. We also provide the evidence, that assessing the microbiota composition at high taxonomic resolution, reveals changes in relative abundance, that may be specific or characteristic for one disease, or a disease-group and might evolve discriminative power. The interactions between bacterial species and strains and moreover the co-abundances must be more deeply investigated before assumptions of the effects of specific bacteria on the host can be made with certainty.

This review focuses on the evidence for neurotherapeutics for Attention Deficit Hyperactivity Disorder (ADHD). EEG-Neurofeedback has been tested for about 45 years with latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Three small studies piloted neurofeedback of frontal activations in ADHD using functional magnetic resonance imaging or near-infrared spectroscopy, finding no superior effects over control conditions. Brain stimulation has been applied to ADHD using mostly repetitive transcranial magnetic and direct current stimulation (rTMS/tDCS). rTMS has shown mostly negative findings on improving cognition or symptoms. Meta-analyses of tDCS studies targeting mostly dorsolateral prefrontal cortex show small effects on cognitive improvements with only two out of three studies showing clinical improvements. Trigeminal nerve stimulation has shown to improve ADHD symptoms with medium effect in one RCT. Modern neurotherapeutics are attractive due to their relative safety and potential neuroplastic effects. However, they need to be thoroughly tested for clinical and cognitive efficacy across settings and beyond core symptoms and for their potential for individualised treatment.

Brain development during the prenatal period is rapid and unparalleled by any other time during development. Biological systems undergoing rapid development are at higher risk for disorganizing influences. Therefore, certain prenatal exposures impact brain development, increasing risk for negative neurodevelopmental outcome. While prenatal exposures have been associated with cognitive and behavioral outcomes later in life, the underlying macroscopic brain pathways remain unclear. Here, we review studies investigating the association between prenatal exposures and infant brain development focusing on prenatal exposures via maternal physical health factors, maternal mental health factors, and maternal drug and medication use. Further, we discuss the need for studies to consider multiple prenatal exposures in parallel and suggest future directions for this body of research.

We take what we see, hear, smell and feel for the reality. However, as neuroscientists, we know that this reality, that is, our perceptual world, is in fact made up by the brain from the processing of the nerve impulses coming from receptors. Ancient Greeks used to think that this perceptual world, sometimes called our 3D movie (Chalmers), is emitted and has its own physical nature. Given how real the 3D movie looks to us, it is still difficult today to consider that all we would be dealing with would be patterns of brain activity The present study thus aimed at testing whether the perceptual world could have some physical existence in addition to that of the neural patterns responsible for it. To achieve that goal, we tried to see whether brains could be sensitive to the 3D movie of others. This, admittedly unusual, operational hypothesis was based on two assumptions. First, brains are sensitive to the 3D movie, as our experience includes reactions to our perceptual world. Second, the physicality at stake does not differ across individuals. We recorded the event-related brain potentials (ERPs) evoked by stimuli of the international affective picture system in pairs of closely-related participants. Most importantly, they could neither see the stimuli simultaneously presented to their partners nor their reactions to them. As in Bouten et al. (2015), around 400 ms after the onset of the stimuli, ERPs started being more positive in inconsistent conditions. Namely, when the two subjects of each pair were presented with the same stimulus whereas they were told it would be a different one and vice-versa (i.e., different-stimuli expected to be same). ERPs were less positive when the two subjects of a pair were presented with the same stimuli and were told they were the same and conversely (i.e., different-stimuli expected to be different). The same experiment was then run in pairs of strangers. No significant effect of consistency on ERPs was observed even though participants could, this time, see, in the very periphery of their visual field, the reactions of their partner to the stimuli. We thus use the results of both studies to support a new version of the emission theory of consciousness and to suggest that the sensitivity to the perceptual world of others may depend on their prior familiarity with it.

Drug delivery to the brain represents a challenge especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as other statins, has shown potential anticancer properties that are difficult to exploit in the CNS. In the present work the physico-chemical, mucoadhesive and permeability enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with different molecular weight (MW) chitosans (LNCchit) prepared by a novel one-pot technique were characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release and permeability across two nasal mucosa models. Results show that all formulations present adequate particle size (below 220 nm), positive surface charge, narrow droplet size distribution (PDI<0.2) and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties dependent on the MW of the coating chitosan. The results of permeation across RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT permeated after 4h for nanocapsules coated with low MW chitosan, high MW chitosan and control SVT was 13.91 ± 0.78 µg, 9.15 ± 1.23 µg and 1.42 ± 0.21 µg respectively. These results were confirmed by the SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.

Controversial hypotheses to explain consciousness exist in many fields of science, psychology and philosophy. Recent experimental findings in quantum cognition and magnetic resonance imaging have added new controversies to the field, suggesting that the mind may be based on quantum computing. Quantum computers process information in quantum bits (qubits) using quantum gates. At a first glance, it seems unrealistic or impossible that the brain can meet the challenges to provide either of these. Nevertheless, we show here why the brain has the incredible ability to perform quantum computing and how that may be realized.

Recent research has revealed surprisingly important connections between animals’ microbiome and social behaviour. Social interactions can affect the composition and function of the microbiome; conversely, the microbiome affects social communication by influencing the hosts’ central nervous system and peripheral chemical communication. These discoveries set the stage for novel research venues focusing on the evolution and physiology of animal social behaviour in relation to microbial transmission strategies. Here, we discuss the emerging roles of teleost fish model candidates and their key potential for advancing research fields linked to sociality and microbial regulation. We argue that fish models, such as the zebrafish, sticklebacks, guppies and cleaner-client dyads, will provide valuable insights into the roles of microbiome in shaping social behaviour and vice versa, while also being of direct relevance to the food and ornamental fish trades.

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.

In the last three decades, the robust scientific data emerged, demonstrating that the immune-inflammatory response is a fundamental component of the pathophysiology of major depressive disorder (MDD). Psychological stress and various inflammatory comorbidities contribute to such immune activation. Still, this is not uncommon that patients with depression do not have defined inflammatory comorbidities, and alternative mechanisms of immune activation need to take place. The gastrointestinal (GI) tract, along with gut-associated lymphoid tissue (GALT), constitutes the largest lymphatic organ in the human body and forms the biggest surface of contact with the external environment. It is also the most significant source of bacterial and food-derived antigenic material. There is a broad range of reciprocal interactions between the GI tract, intestinal microbiota, increased intestinal permeability, activation of immune-inflammatory response, and the CNS that has crucial implications in brain function and mental health. This intercommunication takes place within the microbiota-gut-immune-glia (MGIG) axis, and glial cells are the main orchestrator of this communication. A broad range of factors, including psychological stress, inflammation, dysbiosis and other, may compromise the permeability of this barrier. This leads to excessive bacterial translocation and the excessive influx of food-derived antigenic material that contributes to activation of the immune-inflammatory response and depressive psychopathology. This chapter summarizes the role of increased intestinal permeability in MDD and mechanisms of how the "leaky gut" may contribute to immune-inflammatory response in this disorder.

Psychiatric disorders share the same pattern of longitudinal evolution and have courses that tend to be chronic and recurrent. These aspects of chronicity and longitudinal evolution of psychiatric disorders are currently studied under the neuroprogression framework. Interestingly, considering the plasticity of the brain, it is necessary to emphasize the bidirectional nature of neuroprogression. We review evidence highlighting alterations of the brain associated with the longitudinal evolution of psychiatric disorders from the framework of neuroplastic adaptation to pathology. This new framework highlights that substantial plasticity and remodelling may occur beyond the classic neuroprogressive framework, which is characterized only by loss of grey matter volume, decreased brain connectivity, and chronic inflammation. We also integrate the brain economy concept in the neuroplastic adaptation to pathology framework, emphasizing that to preserve its economy, i.e., function, the brain learns how to cope with the disease by adapting its architecture. This approach can disentangle both the specific pathophysiology of psychiatric symptoms and the adaptation to pathology, thus offering a new framework for both diagnosis and treatment.

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.

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.

Tspo is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of TSPO makes it a good diagnostic biomarker and TSPO could serve as a target for anticancer drug development.

Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory disease of the central nervous system (CNS), characterized by demyelination, axonal degeneration, and cognitive impairment. It also has an important impact on the quality of life of patients and their family members. An estimated 2,500,000 people in the world have multiple sclerosis. Neurophysiological parameters, like sensitivity to demyelination and the strength of excitatory and inhibitory synaptic interactions in the cerebral cortex, can be identified through transcranial magnetic stimulation (TMS) in patients affected by multiple sclerosis (MS). These parameters can be valid and objective parameters that can be correlated with the progression of MS, and can provide reliable indices for the severity of illness and the efficacy of drugs used to treat it. The discovery of specific and detailed neurophysiological parameters as surrogate end points for disease activity could represent an important step in clinical trials. Changes in cortical connectivity have already been demonstrated in MS, but in clinical practice, other measures are usually used to evaluate disease activity. We speculate that TMS may be more effective in identifying disease progression that leads to long-term disability, compared to standard surrogate markers, due to the fact that it represents a direct measure of synaptic transmission(s) in MS.

Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces the activation of the caspase-3 enzyme, which triggers cell apoptosis in an in vivo model of fluid percussion injury (FPI). We analyzed caspase-3 mediated apoptosis by TUNEL staining and PARP and annexin V western blotting. We correlated the neurodegeneration with sensorimotor deficits by conducting the animal behavioral tests including grid walk, balance beam, inverted screen test, and climb test. Our study demonstrated that the excess cell death or neurodegeneration correlated with the neuronal dysfunction and sensorimotor impairments associated with TBI.

The tumor microenvironment is known to have increased levels of cytokines and metabolites, such as glutamate, due to their release from the surrounding cells. A normal cell around the tumor that responds to the inflammatory environment is likely to be subsequently altered. We will discuss how these abnormalities will support tumor survival via the actions of gap junctions (GJs) and hemichannels (HCs) which are composed of hexamer of connexin 43 (Cx43) protein. In particular, we will discuss how GJ intercellular communication (GJIC) in glioma cells, the primary brain tumor, is a regulatory factor and its attenuation leads to tumor invasion. In contrast, the astrocytes, which are normal cells around the glioma, are "hijacked" by tumor cells, either by receiving the transmission of malignant substances from the cancer cells via GJIC, or perhaps via astrocytic HC activity through the paracrine signaling which enable the delivery of these substances to the distal astrocytes. This astrocytic signaling would promote tumor expansion in the brain. In addition, brain metastasis from peripheral tissues has also been known to be facilitated by GJs formed between cerebral vascular endothelial cells and cancer cells. Astrocytes and microglia are generally thought to eliminate cancer cells at the blood brain barrier. In contrast, some reports suggest they facilitate tumor progression as tumor cells take advantage of the normal functions of astrocytes that support the survival of the neurons by exchanging nutrients and metabolites. In summary, GJIC is essential for the normal physiological function of growth and allowing the diffusion of physiological substances. Therefore, whether GJIC is cancer promoting or suppressing may be dependent by what permeates through GJs, when it is active, and to which cells. The nature of GJs, which has been ambiguous in brain tumor progression, will need to be re-visited and understood together with new findings on Cx proteins and HC activities.

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.

A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions. This study presents a comprehensive literature review on the convergence of affective computing, interactive installation art, multi-dimensional sensory stimulation, and artificial intelligence (AI) in measuring emotional responses. It addresses the problem of understanding emotional response and measurement in the context of interactive installation art under artificial intelligence (AI). The study aims to fill the existing research gaps by examining three key aspects: sensory stimulation, multi-dimensional interactions, and engagement, which have been identified as significant contributors to profound emotional responses in interactive installation art. The study proposed approach involves conducting a process analysis of emotional responses to interactive installation art, aiming to develop a conceptual framework that explores the variables influencing emotional responses. The study will formulate hypotheses that make specific predictions about the relationships between sensory stimulation, multi-dimensional interactions, engagement, and emotional responses. By employing the ASSURE model combined with experimental design, the research methodology ensures a systematic and comprehensive study implementation. The implications of this project lie in advancing the understanding of emotional experiences in interactive installation art under AI, providing insights into the underlying mechanisms that drive these experiences. The contributions of this research include bridging the identified research gaps, refining theoretical frameworks, and guiding the design of more impactful and emotionally resonant interactive artworks. Ultimately, this research aims to contribute to the broader field of human-computer interaction and enhance the development of immersive and emotionally engaging interactive installations.

The importance of diet and the gut-brain axis for brain health and cognitive function is increasingly acknowledged. Dietary interventions are tested for their potential to prevent and/or treat brain disorders. Intermittent fasting (IF), the abstinence or strong limitation of calories for 12 to 48 hours, alternated with periods of regular food intake, has shown promising results on neurobiological health in animal models. In this review article, we discuss the potential benefits of IF on cognitive function and the possible effects on the prevention and progress of brain-related disorders in animals and humans. We do so by summarizing the effects of IF which - through metabolic, cellular and circadian mechanisms - lead to anatomical and functional changes in the brain. Our review shows that there is no clear evidence of a positive short-term effect of IF on cognition in healthy subjects. Clinical studies show benefits of IF for epilepsy, Alzheimer’s disease and multiple sclerosis on disease symptoms and progress. Findings from animal studies show mechanisms by which Parkinson’s disease, ischaemic stroke, autism spectrum disorder and mood- and anxiety disorders could benefit from IF. Future research should disentangle whether positive effects of IF hold true regardless of age or the presence of obesity. Also, variations in fasting patterns, total caloric intake and intake of specific nutrients may be relevant components of IF success. Longitudinal studies and Randomized Clinical Trials (RCTs) will provide a window into the long-term effects of IF on the development and progress of brain-related diseases.

Defensive behavior is a function of specific survival circuits, the “aversive brain system”, that are thought to be conserved across vertebrates, and involve threat detection and the organization of defensive responses to reduce or eliminate threat. In mammals, these circuits involve amygdalar and hypothalamic subnuclei and midbrain circuits. The increased interest in teleost fishes as model organisms in neuroscience created a demand to understand which brain circuits are involved in defensive behavior. Telencephalic and habenular circuits represent a “forebrain circuit” for threat processing and organization of responses, being important to mounting appropriate coping responses. Specific hypothalamic circuits organize neuroendocrine and neurovegetative outputs, but are the less well-studied in fish. A “midbrain circuit” is represented by projections to interneurons in the optic tectum which mediate fast escape responses via projections to the central gray and/or the brainstem escape network. Threatening stimuli (especially visual stimuli) can bypass the “high road” and directly activate this system, initiating escape responses. Increased attention to these circuits in an evolutionary framework is still needed.

The medial septum (MS), as part of the basal forebrain, supports many physiological functions, from sensorimotor integration to cognition. With often reciprocal connections with a broad set of peers at all major divisions of the brain, the MS orchestrates oscillatory neuronal activities throughout the brain. These oscillations are critical in generating sensory and emotional salience, locomotion, maintaining mood, supporting innate anxiety, and governing learning and memory. Accumulating evidence points out that the physiological oscillations under septal influence are frequently disrupted or altered in pathological conditions. Therefore, the MS may be a potential target for treating neurological and psychiatric disorders with abnormal oscillations (oscillopathies) to restore healthy patterns or erase undesired ones. Recent studies have revealed that the patterned stimulation of the MS alleviates symptoms of epilepsy. We discuss here that stimulus timing is a critical determinant of treatment efficacy on multiple time scales. On-demand stimulation may dramatically reduce side effects by not interfering with normal physiological functions. A precise pattern-matched stimulation through adaptive timing governed by the ongoing oscillations is essential to effectively terminate pathological oscillations. The time-targeted strategy for the MS stimulation may provide an effective way of treating multiple disorders including Alzheimer’s disease, anxiety/fear, schizophrenia, and depression, as well as pain.

Introduction: Dementia is a cognitive decline with patients often exhibit behavioural and psychological symptoms, severely affecting the quality of life and placing a heavy burden on caregivers. Acupressure has reported benefits for dementia. This study aims to critically review the available evidence for its use as a non-pharmacological therapy. Methods: Systematic search of major research databases for human clinical trials using acupressure as an intervention for dementia patients was conducted. Results were synthesised for the effects of acupressure on various outcome measures of interest for dementia.Results: Twelve clinical trials (N=973), including eight randomised control studies, were included in this review. The study sample was predominantly institutionalised residents with moderate to severe dementia. Baihui (GV20), Shenmen (HT7), Fengchi (GB20), Neiguan (PC6), Sanyinjiao (SP6), and Yingtang (EX-HN3) were the most used acupoints for intervention. Acupressure techniques employed in these clinical trials vary greatly with no standardised approach. This review finds inconsistent evidence in the effectiveness of acupressure in reducing agitation and behavioural disturbances. However, the treatment appears to improve their ease of care and reduce physical stress. Affixing acupressure devices on selected acupoints can also potentially improve psychiatric pain, anxiety, and depression. Long-term (6 months) treatment can potentially improve the cognitive function, activities of daily living, and quality of life of patients with mild to moderate dementia. The effect of acupressure on sleep disturbances remains unclear. Conclusion: More high-quality research on acupressure is needed to fill the gaps in knowledge and inform better care for dementia patients in the future.

Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its copy number alteration (CNA) and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2 and 12p13.31 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.

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.

This work promotes new methods in Mathematical Modeling, consisting in the use of the methods of Non-standard Analysis in Topoi, having as its main purpose, the mathematical definitions of the pseudoparticles from the title, with arguments from Biology/Physiology (Mathematical Neuroscience), Physics (String Theory and Emergent Quantum Mechanics), and Cybernetics (Global Brain, including Natural and Artificial Intelligence). The connections between brain and mind will be scketched via the genetic/epigenetic interplay. The topoi model the intuitionistic logic (multi-valued) and have been used in Quantum Physics while Non-Standard Analysis in SET (= the Category of sets) has been applied in Mathematical Economics; topics from Theory of Categories were also used in the study of Consciousness; however, the combination topoi - non-standard analysis was never used until now in Applied Mathematics. Another important objective is to produce progress in this aria of Pure Mathematics also - the build of non-standard analysis in classes of topoi, already used in Physics. We propose the logic of non-standard extensions in topoi as a model of the human thinking (based on infons/receptons), these theories representing new top and very difficult results in Abstract Mathematics either.

Enzyme replacement therapy (ERT) improves the somatic manifestations in mucopolysaccharidoses (MPS))．However, because intravenously administered enzymes cannot cross the blood brain barrier (BBB), ERT is ineffective against the progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed in patients with neuronopathic MPS. Attempts to surmount this problem have been made with intrathecal and intracerebroventricular ERT intend to achieve CNS effects, but the burdens on patients are inimical to long-term multiple administrations. However, after pabinafusp alfa, a human iduronate-2-sulfatase fused with a BBB-crossing anti-transferrin receptor antibody, showed both central and peripheral efficacy in mice model, subsequent clinical trials in a total of 62 patients with MPS-II (Hunter syndrome) in Japan and Brazil substantiated this dual efficacy and provided an acceptable safety profile. To date, pabinafusp alfa is the only approved intravenous ERT effective against both the somatic and CNS symptoms of patients with MPS-II. This article summarizes the hitherto obtained preclinical and clinical evidence associated with this drug, and discusses the preclinical, translational and clinical challenges of evaluating, ameliorating and preventing the neurodegeneration in patients with MPS-II.

In this paper, we propose methods for brain tumor detection in MRI images based on ensemble learning. We build upon prior research on ensemble methods by testing the concatenation of pre-trained models: features extracted via transfer learning are merged and segmented by classification algorithms or a stacked ensemble of those algorithms. The proposed approach achieved accuracy scores of 0.98 , outperforming a benchmark VGG-16 model. Considerations to granular computing are given in the paper as well.

Over past decades, a frequent co-morbidity of cerebrovascular pathology and Alzheimer's disease pathology has been observed. Numerous published studies indicate that preservation of healthy cerebrovascular endothelium can be an important therapeutic target. By incorporating appropriate drug(s) into biomimetic (lipid cubic-phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type 1 (i.e., SR-BI), and crosses the blood-brain barrier. This targeting allows for various Alzheimer’s-related cell types to be simultaneously searched out for localized drug treatment in vivo.

Astrocytes are essential for normal brain development and functioning. They respond to brain injury and disease through a process referred to as reactive astrogliosis, where the reactivity is highly heterogenous and context dependent. Reactive astrocytes are active contributors to brain pathology and can exert beneficial, detrimental, or mixed effects following brain insults. Transforming growth factor-β (TGF-β) has been identified as one of the key factors regulating astrocyte reactivity. Genetic and pharmacological manipulation of TGF-β signaling pathway in animal models of CNS injury and disease alters pathological and functional outcomes. This review aims to provide recent understanding regarding astrocyte reactivity and TGF-β signaling in brain injury, aging, and neurodegeneration. Further, it explores how TGF-β signaling modulates astrocyte reactivity and function.

In Kenya, millions of children have limited access to nurturing care. With the COVID-19 pandemic, it is anticipated that vulnerable children will bear the biggest brunt of the direct and indirect impacts of the pandemic. This review aimed to deepen understanding of the effects of COVID-19 on nurturing care from conception to four years of age, a period where the care of children is often delivered through caregivers or other informal platforms. The review has drawn upon the empirical evidence from previous pandemics and epidemics, and anecdotal and emerging evidence from the ongoing COVID-19 crisis. Multifactorial impacts fall into five key domains: direct health; health and nutrition systems, economic, social and child protection, and child development and early learning. The review proposes program and policy strategies to guide the re-orientation of nurturing care, prevent the detrimental effects associated with deteriorating nurturing care environments, and support the optimal development of the youngest and most vulnerable children. These include the provision of cash transfers and essential supplies for vulnerable households, and strengthening of community-based platforms for nurturing care. Further research on COVID-19 and the ability of children’s ecology to provide nurturing care is needed, as is further testing of new ideas.

The question of what generates conscious experience has mesmerized thinkers since the dawn of humanity, yet its origins remain a mystery. The topic of consciousness has gained traction in recent years, thanks to the development of large language models that now arguably pass the Turing test, an operational test for intelligence. However, intelligence and consciousness are not related in obvious ways, as anyone who suffers from a bad toothache can attest - pain generates intense feelings and absorbs all our conscious awareness yet nothing particularly intelligent is going on. Still, in the hard sciences, this topic is frequently met with skepticism because to date no protocol to measure the content or intensity of conscious experiences in an observer-independent manner has been agreed upon. Here we present a novel proposal: Conscious experience arises whenever a quantum mechanical superposition forms. Our proposal has several implications: First, it suggests that the structure of the superposition determines the qualia of the experience. Second, quantum entanglement naturally solves the binding problem, ensuring the unity of phenomenal experience. Finally, a moment of agency may coincide with the formation of a superposition state. We outline a research program to experimentally test our conjecture via a sequence of quantum biology experiments. Applying these ideas opens up the possibility of expanding human experience through brain-quantum computer interfaces.

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.

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.

How can neuroscience help everyone to live and care for our confined brains? Understanding and studying human behaviour allows us to measure the impact of such confinement on each of us and to identify those who need help. The challenges are to understand the psychological repercussions following confinement and to understand how neuroscience and neurotechnology can be very interesting tools for dealing with the health crisis. Neuroscience is changing our traditional philosophical and ethical views by providing information about the biological basis of our moral behaviour. The exception of the brain is at the heart of neuroethical thinking and discourse. Neuroethics is an interdisciplinary discipline placed at the intersection between the human sciences and the neurosciences, and aims to help understand how knowledge and research in neurosciences and neurotechnologies will affect the future of society, their impact on humans, relationships, daily life, the labour market ... but also how they can help and provide solutions and answers to the questions of citizens in a health crisis. But it's a double-edged sword, collecting and analyzing brain data in real time seems to be increasingly simple and within everyone's reach, without having the hindsight of the real meaning of these data, allowing one day to read people's thoughts, control them and manipulate them. It is becoming clear that the boundaries between medical and non-medical uses of neuroscience and neurotechnology are becoming very porous, inviting us to reflect on neuroethical issues in order to put safeguards on these uses.

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.

Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cells transplantation, may hold promise as stroke therapy because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery. Recent evidence has implicated mitochondria, organelles with a central role in energy metabolism and stress response, in stroke progression. Recognizing that stem cells offer a source of healthy mitochondria, potentially transferrable into ischemic cells, may provide a new therapeutic tool. To this end, deciphering cellular and molecular processes underlying dysfunctional mitochondria may reveal innovative strategies for stroke therapy. Here, we review recent studies capturing the intimate participation of mitochondrial impairment in stroke pathology, and showcase promising methods of healthy mitochondria transfer into ischemic cells, to critically evaluate the potential of mitochondria-based stem cell therapy for stroke.

Sedation is a ubiquitous practice in ICUs and NCCUs. It has the benefit of reducing cerebral energy demands, but also precludes an accurate neurologic assessment. Because of this, sedation is intermittently stopped for the purposes of a neurologic assessment, which is termed a neurologic wake-up test (NWT). NWTs are considered to be the gold-standard in continued assessment of brain-injured patients under sedation. NWTs also produce an acute stress response that is accompanied by elevations in blood pressure, respiratory rate, heart rate, and ICP. Utilization of cerebral microdialysis and brain tissue oxygen monitoring indicates that this is not mirrored by alterations in overall cerebral metabolism, and seldom affects oxygenation. The hard contraindications for the NWT are preexisting intracranial hypertension, barbiturate treatment, status epilepticus, and hyperthermia. However, hemodynamic instability, sedative use for primary ICP control, and sedative use for severe agitation or respiratory distress are considered significant safety concerns. Despite ubiquitous recommendation, it is not clear if additional clinically relevant information is gleaned through its use, especially with the contemporaneous utilization of multimodality monitoring. Various monitoring modalities provide unique and pertinent information about neurologic function, however, their role in improving patient outcomes and guiding treatment plans has not been fully elucidated. There is a paucity of information pertaining to the optimal frequency of NWTs, and if it differs based on type of injury. Only one concrete recommendation was found in the literature, exemplifying the uncertainty surrounding its utility. The most common sedative used and recommended is propofol because of its rapid onset, short duration, and reduction of cerebral energy requirements. Dexmedetomidine may be employed to facilitate serial NWTs, and should always be used in the non-intubated patient or if propofol infusion syndrome (PRIS) develops. Midazolam is not recommended due to tissue accumulation and residual sedation confounding a reliable NWT. Thus, NWTs are well tolerated in most patients and remain recommended as the gold-standard for continued neuromonitoring. Predicated upon one expert panel, they should be performed at least one time per day. Propofol or dexmedetomidine are the main sedative choices, both enabling a rapid awakening and consistent NWT.

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 specicity. 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 innity 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 signicantly. 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, scientic 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 proles 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.

Purpose: Dysarthria, a neurological injury of the motor component of the speech circuitry, is of common consequences of traumatic brain injury (TBI). Palilalia is a speech disorder characterized by involuntary repetition of words, phrases, or sentences. Based on the evidence supporting the effectiveness of transcranial direct current stimulation (tDCS) in some speech and language disorders, we hypothesized that using tDCS would enhances the effectiveness of speech therapy in a client with chronic dysarthria following TBI. Method: We applied the constructs of the “Be Clear” protocol, a relatively new approach in speech therapy in dysarthria, together with tDCS on a chronic subject who affected by dysarthria and palilalia after TBI. Since there was no research on the use of tDCS in such cases, regions of interest (ROIs) were identified based on deviant brain electrophysiological patterns in speech tasks and resting state compared with normal expected patterns using the Quantitative Electroencephalography (QEEG) analysis. Results: Measures of perceptual assessments of intelligibility, an important index in the assessment of dysarthria, ​​were superior to the primary protocol results immediately and 4 months after intervention. We did not find any factor other than the use of tDCS to justify this superiority. The percentage of repeated words, an index in palilalia assessment, had a remarkable improvement immediately after intervention but fell somewhat after 4 months. We justified this case with subcortical origins of palilalia. Conclusion: Our present case-based findings suggested that applying tDCS together with speech therapy may improve intelligibility in similar case profiles as compared to traditional speech therapy. To reconfirm the effectiveness of the above approach in cases with dysarthria following TBI, more investigation need to be pursued.

The acetylcholinesterase (AChE) inhibitors are the main drugs for symptomatic treatment of neurodegenerative disorders like Alzheimer’s disease. A recently designed, synthesized and tested hybrid compound between the AChE inhibitor galantamine (GAL) and the antioxidant polyphenol curcumin (CU) showed high AChE inhibition in vitro. Here, we describe tests for acute and short-term toxicity in mice as well as antioxidant tests on brain homogenates measured the levels of malondialdehide (MDA) and glutathione (GSH). Haematological and serum biochemical analyses were also performed. In the acute toxicity tests, the novel AChE inhibitor given orally in mice showed LD50 of 49 mg/kg. The short-term administration of 2.5 and 5 mg/kg did not show toxicity. In the ex vivo tests, the GAL-CU hybrid performed better than GAL and CU themselves. In a dose of 5 mg/kg, it demonstrates 25% reduction in AChE activity, 28% and 73% increase in the levels of MDA and GSH, respectively. No significant changes in blood biochemical data were observed. The GAL-CU hybrid is a novel non-toxic AChE inhibitor with high antioxidant activity which makes it a perspective multitarget drug candidate for treatment of Alzheimer’s disease.

Mammalian genomes encode tens of thousands of long-noncoding RNAs (lncRNAs), which are capable of interactions with DNA, RNA and protein molecules, thereby enabling a variety of transcriptional and post-transcriptional regulatory activities. Strikingly, about 40% of lncRNAs are expressed specifically in the brain in precisely regulated temporal and spatial expression patterns. In stark contrast to the highly conserved repertoire of protein-coding genes, thousands of new lncRNAs have appeared during primate nervous system evolution with hundreds of human-specific lncRNAs. Their evolvable nature and the myriad of potential functions make lncRNAs ideal candidates for drivers of human brain evolution. The human brain displays the largest relative volume of any animal species and the most remarkable cognitive abilities. In addition to brain size, structural reorganization and adaptive changes represent crucial hallmarks of human brain evolution. LncRNAs are increasingly reported to be involved in neurodevelopmental processes including proliferation, neurite outgrowth and synaptogenesis, as well as in neuroplasticity, suggested to underlie human brain evolution. Hence, evolutionary human brain adaptations are proposed to be essentially driven by lncRNAs, which will be discussed in this review.

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments associated with metabolic factors and increases the cellular vulnerability to develop the age-related increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

Key features of glycogen metabolism in excitable tissues are not well-explained by current concepts. Glycogen stores in brain and skeletal muscle are generally considered to function as local glucose reserves, to be utilized during transient mismatches between glucose supply and demand; however, quantitative measures show that blood glucose supply is likely never rate-limiting for energy metabolism in either brain or muscle under physiological conditions. These tissues nevertheless do normally utilize glycogen during intervals of increased energy demand, despite the availability of free glucose, and despite the ATP cost of cycling glucose through glycogen polymer. This seemingly wasteful shunt can be explained by considering the effect of glycogenolysis on the amount of energy derived from ATP (ΔG’ATP). ΔG’ATP is diminished by elevations in Pi, such as occur at sites of rapid ATP hydrolysis and net phosphocreatine consumption. Glycogen utilization counters this effect by sequestering Pi in glycolytic metabolites (glycogen_n + Pi → glycogen_n-1 + glucose-1-phosphate → phosphorylated glycolytic intermediates), and thereby maintains the amount of energy obtained from ATP at sites of rapid ATP consumption. This thermodynamic effect may be particularly important in the narrow, spatially constricted astrocyte processes that ensheath neuronal synapses. This effect can also explain the co-localization of glycogen and cytosolic phosphocreatine in brain astrocytes, glycolytic super-compensation in brain when glycogen is not available, and aspects of exercise physiology in muscle glycogen phosphorylase deficiency (McArdle’s disease).

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).

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.

(1) Background: Stimulating oropharyngeal transient receptor potential (TRP) channels inhibits muscle cramping by triggering a supraspinal reflex to reduce α-motor neuron hyperexcitability. This study investigated whether longer stimulation of TRP channels via mouth rinsing with PJ is more effective than drinking PJ at inhibiting an electrically induced muscle cramp (EIMC); (2) Methods: Tibial nerve in 11 cramp-prone adults were percutaneously stimulated to elicit an EIMC of flexor hallucis brevis in three trials 1-week apart. At cramp onset participants received mouth rinsing and expelling PJ (25 mL), ingesting PJ (1 mL∙kg-1 body-mass [BM]), or ingesting water (1 mL∙kg-1 BM). Cramp onset and offset by electromyography and severity of discomfort was recorded using a visual analogue scale (VAS); (3) Results: Median time to cramp cessation as a percentage of water was 82.8% ± 14.634 and 68.6% ± 47.782 for PJ ingestion and mouth rinse respectively. These results had large variability and no statistically significant difference was observed. There were also no differences in perceived cramp discomfort between conditions, despite hazard ratios for time to VAS = 0 higher than water for PJ ingestion (22%) and mouth rinse (35%) (p = 0.66 and 0.51 respectively); (4) Conclusions: Data suggest no difference in cramp duration and perceived discomfort between PJ and water.

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.

Background: Maladaptive neuroplasticity related learned response in substance use disorder (SUD) can be ameliorated using non-invasive brain stimulation (NIBS); however, inter-individual variability needs to be addressed for clinical translation. Objective: Our first objective was to develop a hypothesis for NIBS for learned response in SUD based on competing neurobehavioral decision systems model. Next objective was to conduct computational simulation of NIBS of cortico-cerebello-thalamo-cortical (CCTC) loop in cannabis use disorder (CUD) related dysfunctional “cue-reactivity” – a closely related construct of “craving” that is a core symptom. Our third objective was to test the feasibility of our neuroimaging guided rational NIBS approach in healthy humans. Methods: “Cue-reactivity” can be measured using behavioral paradigms and portable neuroimaging, including functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG), metrics of sensorimotor gating. Therefore, we conducted computational simulation of NIBS, including transcranial direct current stimulation(tDCS) and transcranial alternating current stimulation(tACS) of the cerebellar cortex and deep cerebellar nuclei(DCN), of the CCTC loop for its postulated effects on fNIRS and EEG metrics. We also developed a rational neuroimaging guided NIBS approach for cerebellar lobule (VII) and prefrontal cortex based on healthy human study. Results: Simulation study of cerebellar tDCS induced gamma oscillations in the cerebral cortex while tTIS induced gamma-to-beta frequency shift. Experimental fNIRS study found that 2mA cerebellar tDCS evoked similar oxyhemoglobin(HbO) response in-the-range of 5x10-6M across cerebellum and PFC brain regions (=0.01); however, infra-slow (0.01–0.10 Hz) prefrontal cortex HbO driven(phase-amplitude-coupling, PAC) 4Hz, ±2mA (max.) cerebellar tACS evoked HbO in-the-range of 10-7M that was statistically different (=0.01) across those brain regions. Conclusion: Our healthy human study showed the feasibility of fNIRS of cerebellum and PFC as well as fNIRS-driven ctACS at 4Hz that may facilitate cerebellar cognitive function via the frontoparietal network. Future work needs to combine fNIRS with EEG for multi-modal imaging.

‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain func-tion and behavior. Moreover, gut microbiota composition constantly controls microglia matura-tion as revealed by morphological observations and gene expression analysis. However, it is un-clear whether gut microbiota influences microglia functional properties and crosstalk with neu-rons, known to shape and modulate synaptic development and function. Here, we investigated how antibiotic mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. The effect of dysbiosis on neuronal functions are mediated by microglia-neuron cross-talk through the CX3CL1-CX3CR1 axis, as antibiotics treatment of CX3CR1 deficient mice, mod-ulates microglia density and processes rearrangement leaving unaltered synaptic function. To-gether, our findings show that the antibiotics alteration of gut microbiota impairs synaptic effi-cacy, probably through CX3CL1-CX3CR1 signaling supporting microglia as a major player in in the gut-brain axis, and in particular in the gut microbiota-to-neuron communication pathway.

A frequent co-morbidity of cerebrovascular pathology and Alzheimer's disease pathology has been observed over past decades. Accordingly, much evidence has been reported which indicates that microvascular endothelial dysfunction, due to cerebrovascular risk factors (e.g., atherosclerosis, obesity, diabetes, smoking, hypertension, aging), precedes cognitive decline in Alzheimer's disease and contributes to its pathogenesis. By incorporating appropriate drug(s) into biomimetic (lipid cubic phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type I (i.e., SR-BI), and crosses the blood-brain barrier (BBB). Such targeting allows for various Alzheimer's-related cell types to be simultaneously searched out, in vivo, for localized drug treatment. This in vivo targeting advantage may be particularly important for repurposing an FDA-approved drug, especially one which has shown the added ability to restore some cognitive functions in certain animal models of Alzheimer's disease (e.g., the anticancer drug bexarotene); this (candidate repurposing) drug up to now, by itself (i.e, without nanocarrier), displayed poor CNS penetration in human subjects.

During the exploration of the surrounding environment, the brain links together external inputs, giving rise to perception of a persisting object. During imaginative processes, the same object can be recalled in mind even if it is out of sight. Here, topological theory of shape provides a mathematical foundation for the notion of persistence perception. In particular, we focus on ecological theories of perception, that account for our knowledge of world objects by borrowing a concept of invariance in topology. We show how a series of transformations can be gradually applied to a pattern, in particular to the shape of an object, without affecting its invariant properties, such as boundedness of parts of a visual scene. High-level representations of objects in our environment are mapped to simplified views (our interpretations) of the objects, in order to construct a symbolic representation of the environment. The representations can be projected continuously to an environmental object that we have seen and continue to see, thanks to the mapping from shapes in our memory to shapes in Euclidean space.

Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking, chemo and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood brain barrier, immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to 1) optimize delivery of oncolytic viruses beyond the blood brain barrier; 2) trigger inflammatory immune responses in and around tumors; and 3) use of multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.

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.

Objective: It was aimed to investigate the cerebral vascular territories in stroke patients with NVAF as an etiologic factor. Material and Methods: A total of 104 patients who were referred to our hospital between January 2015 and September 2016, who were over 55 years of age, identified or documented as having a standard ECG or Holter ECG record on their medical history, and diagnosed with stroke were included. Our study was designed as a retrospective analysis of prospective data. Detailed history, physical examination and electrocardiography (ECG) evaluations of the patients were performed. Descriptive statistics were used in the detection of findings, and t-test, Pearson-square test and Fisher's exact test were used for differences analysis. Results: 53.8% (N = 56) of the patients were male and 46.2% (N = 48) were female. The mean age was 73.5. MCA was the most common site of vascular involvement in NVAF-dependent strokes. In MCA vascular territory, ischemic infarcts were detected most frequently in the upper and lower divisions. SCA and PCA followed MCA. Approximately 64% of the NVAF-related strokes were anterior circulation infarction (ASE) and 22% were posterior circulation infarct (PSE). There was a significant difference in age and past stroke history factors in favor of ASE (p<0.05). There was no significant difference between ASE and PSE in HT, cardiac history and DM factors (p>0.05). Conclusion: It was emphasized that the area of the vessel that underwent ischemia in the acutely displayed infarcts and the etiological factor for this vessel area could be predicted

The prolonged lockdown imposed to contain the COVID-19 pandemic prevented many people from direct contact with nature and greenspaces, raising alarms for a possible worsening of mental health. This study investigates the effectiveness of a simple and affordable remedy for improving psychological well-being, based on audio-visual stimuli brought by a short computer video showing forest environments, with an urban video as a control. Randomly selected participants were assigned the forest or urban video, to look at and listen early in the morning, and filled questionnaires. In particular, the State-Trait Anxiety Inventory (STAI) Form Y, collected in baseline condition and at the end of the study, and the Part II of the Sheehan Patient Rated Anxiety Scale (SPRAS), collected every day immediately before and after watching the video. The virtual exposure to forest environments showed effective to reduce perceived anxiety levels in in people forced by lockdown in limited spaces and environmental deprivation. Although significant, the effects were observed only in the short term, highlighting the limitation of the virtual experiences. The reported effects might also represent a benchmark to disentangle the determinants of health effects due to real forest experiences, for example, the inhalation of biogenic volatile organic compounds (BVOC).

Abstract: Tumor-targeting and blood-brain barrier (BBB)-penetrating are highly desirable for the treatment of glioma. In this study, we developed Pep-1&borneol-bifunctionalized carmustin-loaded micelles (Pep-1/Bor/CMS-M) capable of targeting to IL-13 receptor-overexpressed glioma and penetrating the brain microvascular endothelial cells-associated physiologic barriers. Pep-1/Bor/CMS-M were nearly spherical particles with a dimeter of 32.6 ± 1.1 nm and zeta potential of -21.3 ± 3.1 mV. Carmustine (CMS) released from Pep-1/Bor/CMS-M in pH 7.4 was significantly faster than in acidic environments. In human glioma BT325 cellular studies, Pep-1/Bor/CMS-M remarkably increased the cytotoxicity, notably improved the internalization and effectively induced the cell apoptosis. Likewise, in human brain microvascular endothelial cells (HBMEC) cells, Pep-1/Bor/CMS-M obviously promoted the cellular uptake, rapidly decreased the transepithelial electrical resistance (TEER) and thereby of enhancing the ability of penetration. In orthotopic Luc-BT325 glioma tumor-bearing nude mouse models, the stronger fluorescence signal and longer retention were observed in brain tissues compared with other controls, after single administration of DiD-labelled Pep-1/Bor/M (DiD/Pep-1/Bor/M). Importantly, Pep-1/Bor/CMS-M displayed the strongest inhibition of tumor growth, the longest survival period and low systemic toxicity in treating orthotopic glioma tumor-bearing nude mice. Simultaneous functionalization of Pep-1 and borneol offers a novel strategy for designing CMS-based nanomedicine and precisely treating glioma.

Cancer is the second biggest cause of death in children. With the development of chemotherapy, there is a substantial increase in overall survival rate over recent 30 years. However, the overall mortality rate in children with cancer still remains 25%, and many survivors experience a decline in overall quality of life and long-term adverse effects caused by treatments. Although cancer cells share common characteristics, pediatric cancers are different from adult cancers in their prevalence, mutation load, and drug response. Therefore, there is an urgent unmet need to develop therapeutic approaches specifically designed for children with cancer. Nanotechnology can potentially overcome the deficiencies of conventional methods of administering chemotherapy and ultimately improve clinical outcomes. The nanoparticle-based drug delivery systems can decrease the toxicity of therapy, provide a sustained or controlled drug release, improve pharmacokinetic properties of loading contents, and achieve a targeted drug delivery with achievable modifications. Further, therapeutic approaches based on combining nanoformulated drugs with novel immunotherapeutic agents are emerging. In this review, we discuss the recently developed nanotechnology-based strategies for treating blood and solid pediatric cancers.

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.

The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria and toxic proteins significantly contributes to the correspondent recovery processes. However, understanding of the meningeal lymphatics functions is a challenging problem. The exploration of mechanisms of lymphatic communication with brain fluids as well as the role of the lymphatic system in the brain drainage, clearance and recovery are still in its infancy. Here we review novel concepts on the anatomy and physiology of the lymphatics in the brain, which warrant a substantial revision of our knowledge about the role of lymphatics in the rehabilitation of the brain functions after neural pathologies. We discuss a new vision on how to recruit the meningeal lymphatics by the opening of blood-brain barrier as a trigger mechanism of activation of the meningeal lymphatic drainage. This leads to innovative strategies in neurorehabilitation therapy.

Deep learning has shown remarkable results in every field, especially in the biomedical field, due to its ability to exploit large-scale datasets. A convolutional neural network (CNN) is a widely used deep learning approach to solve medical imaging problems. Over the past few years, many studies have focused on CNN-based techniques for brain tumor diagnosis. There are, however, still some critical challenges that CNNs face towards clinic application. This study presents a comprehensive review of current literature that involves CNN architectures for brain tumor classification. We compare the key achievements in the performance evaluation metrics of the applied classification algorithms. In addition, this review assesses the clinical effectiveness of the included studies to elaborate on the limitations and directions of this area for future work. No review focusing on the clinical effectiveness of previous works in this field has been published. We believe that this study has the potential to elevate the application of CNN-based deep learning methods in clinical practice and also can be a quick reference for biomedical researchers who are interested in this field.

Perception and motor interaction with physical surroundings can be analyzed by the changes in probability laws governing two possible outcomes of neuronal activity, namely the presence or absence of spikes (binary states). Perception and motor interaction with physical environment are accounted partly by the reduction in entropy within the probability distributions of binary states of neurons in distributed neural circuits, given the knowledge about the characteristics of stimuli in physical surroundings. This reduction in the total entropy of multiple pairs of circuits in networks, by an amount equal to the increase of mutual information among them, occurs as sensory information is processed successively from lower to higher cortical areas or between different areas at the same hierarchical level but belonging to different networks. The increase in mutual information is partly accounted by temporal coupling as well as synaptic connections as proposed by Bahmer and Gupta [1]. We propose that robust increases in mutual information, measuring the association between the characteristics of sensory inputs and neural circuits connectivity patterns, are partly responsible for perception and successful motor interactions with physical surroundings. It is also argued that perception from a sensory input is the result of networking of many circuits to a common circuit that primarily processes the given sensory input.

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.

Thought runs through the mind like blood runs through our body to keep us alive. Like the mind, the body does not stay inert and is in constant motion. Not a single cell in our body is left inert unless cell is under stress or dying. These scenarios are reflected upon when a person is sick, the person lies in bed with less movement; however, is active when the person is healthy. The topic of mechanical stimulation has emerged due to the increasing understanding of the physical stimulations we face each day. Further understanding of the mechanically-regulated mechanism can help us explore the pathological events in a disease. Here, we reviewed the role of sensory proteins in pathological events that are observed in cardiomyopathy, cancer, respiratory, renal, obesity, genetics, physical injury and bacterial infection. Taken together, sensory proteins are mechanically-activated which assist reception of external physical stimulation and convert into biochemical to trigger intracellular signaling cascade.

Modeling brain dynamics to better understand and control complex behaviors underlying various cognitive brain functions are of interests to engineers, mathematicians, and physicists from the last several decades. With a motivation of developing computationally efficient models of brain dynamics to use in designing control-theoretic neurostimulation strategies, we have developed a novel data-driven approach in a long short-term memory (LSTM) neural network architecture to predict the temporal dynamics of complex systems over an extended long time-horizon in future. In contrast to recent LSTM-based dynamical modeling approaches that make use of multi-layer perceptrons or linear combination layers as output layers, our architecture uses a single fully connected output layer and reversed-order sequence-to-sequence mapping to improve short time-horizon prediction accuracy and to make multi-timestep predictions of dynamical behaviors. We demonstrate the efficacy of our approach in reconstructing the regular spiking to bursting dynamics exhibited by an experimentally-validated 9-dimensional Hodgkin-Huxley model of hippocampal CA1 pyramidal neurons. Through simulations, we show that our LSTM neural network can predict the multi-time scale temporal dynamics underlying various spiking patterns with reasonable accuracy. Moreover, our results show that the predictions improve with increasing predictive time-horizon in the multi-timestep deep LSTM neural network.

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.

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs in glioblastoma multiforme (GB) because it is highly expressed in GB stem cells and in brain-blood barrier (BBB), the peculiar endothelium surrounding brain. Inhibiting Pgp activity in BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp < 50 nM, in primary human BBB cells and in patients-derived GB, from which we isolated differentiated/adherent cells (AC, i.e. Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e. Pgp-positive/doxorubicin-resistant cells). At 1 nM, 3 compounds increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring necrosis, apoptosis and reduction in cell viability induced by doxorubicin. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations, that effectively reduce Pgp activity in BBB and GB, and can improve chemotherapy efficacy in this tumor.

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. In the present study, we aimed to determine whether treatment with resveratrol reduces reactive oxygen species (ROS) generation in the brain, thereby reducing cognitive impairment in rats with angiotensin II (Ang-II)-induced early AD. Male WKY rats with Ang-II-induced AD were treated with losartan or resveratrol for 2 weeks. Our results revealed that treatment with resveratrol (10 mg/kg/day) decreased blood pressure, increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased ROS production in the nucleus tractus solitarius (NTS) in the Ang-II groups. In addition, inhibition of Tau^T231 phosphorylation in the hippocampus using resveratrol significantly abolished Ang-II-induced expression of Ab precursors, active caspase 3, and glycogen synthase kinase 3b (GSK-3b)^Y216 while increasing Akt^S473 phosphorylation. Notably, resveratrol reversed impairments in hippocampal-dependent contextual memory induced by deleting NADPH oxidase and NOX2. Overall, our results suggest that resveratrol exerts neuroprotective effects against memory impairment and hippocampal damage in a rat model of early stage AD by reducing oxidative stress. These novel findings indicate that resveratrol may represent a pharmacological option for patients with hypertension at a risk of AD during old age.