Search results for: the self and the brain

Authors: Igor Faulmann, Arnaud Saj, Roland Maurer

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Spatial cognition consists in a plethora of high level cognitive abilities: among them, the ability to learn and to navigate in large scale environments is probably one of the most complex skills. Navigation is thought to rely on the ability to read a cognitive map, defined as an allocentric representation of ones environment. Those representations are of course intimately related to the two geometrical primitives of the environment: distance and direction. Also, many recent studies point to a predominant hippocampal and para-hippocampal role in spatial cognition, as well as in the more specific cluster of navigational skills. In a previous study in humans, we used a newly validated test assessing cognitive map processing by evaluating the ability to judge relative distances and directions: the CMRT (Cognitive Map Recall Test). This study identified in topographically disorientated patients (1) behavioral differences between the evaluation of distances and of directions, and (2) distinct causality patterns assessed via VLSM (i.e., distinct cerebral lesions cause distinct response patterns depending on the modality (distance vs direction questions). Thus, we hypothesized that: (1) if the CMRT really taps into the same resources as real navigation, there would be hippocampal, parahippocampal, and parietal activation, and (2) there exists underlying neuroanatomical and functional differences between the processing of this two modalities. Aiming toward a better understanding of the neuroanatomical correlates of the CMRT in humans, and more generally toward a better understanding of how the brain processes the cognitive map, we adapted the CMRT as an fMRI procedure. 23 healthy subjects (11 women, 12 men), all living in Geneva for at least 2 years, underwent the CMRT in fMRI. Results show, for distance and direction taken together, than the most active brain regions are the parietal, frontal and cerebellar parts. Additionally, and as expected, patterns of brain activation differ when comparing the two modalities. Furthermore, distance processing seems to rely more on parietal regions (compared to other brain regions in the same modality and also to direction). It is interesting to notice that no significant activity was observed in the hippocampal or parahippocampal areas. Direction processing seems to tap more into frontal and cerebellar brain regions (compared to other brain regions in the same modality and also to distance). Significant hippocampal and parahippocampal activity has been shown only in this modality. This results demonstrated a complex interaction of structures which are compatible with response patterns observed in other navigational tasks, thus showing that the CMRT taps at least partially into the same brain resources as real navigation. Additionally, differences between the processing of distances and directions leads to the conclusion that the human brain processes each modality distinctly. Further research should focus on the dynamics of this processing, allowing a clearer understanding between the two sub-processes.

Keywords: cognitive map, navigation, fMRI, spatial cognition

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Authors: A. V. Sokolov, S. V. Vorobyev, A. Yu. Efimtcev, V. Yu. Lobzin, I. A. Lupanov, O. A. Cherdakov, V. A. Fokin

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Alzheimer’s disease (AD) is the most common form of dementia. Different brain regions are involved to the pathological process of AD. The purpose of this study was to evaluate brain activation by visual memory task in patients with Alzheimer's disease and determine correlation between memory impairment and atrophy of memory specific brain regions of frontal and medial temporal lobes. To investigate the organization of memory and localize cortical areas activated by visual memory task we used functional magnetic resonance imaging and to evaluate brain atrophy of patients with Alzheimer's disease we used voxel-based morphometry. FMRI was performed on 1.5 T MR-scanner Siemens Magnetom Symphony with BOLD (Blood Oxygenation Level Dependent) technique, based on distinctions of magnetic properties of hemoglobin. For test stimuli we used series of 12 not related images for "Baseline" and 12 images with 6 presented before for "Active". Stimuli were presented 3 times with reduction of repeated images to 4 and 2. Patients with Alzheimer's disease showed less activation in hippocampal formation (HF) region and parahippocampal gyrus then healthy persons of control group (p<0.05). The study also showed reduced activation in posterior cingulate cortex (p<0.001). Voxel-based morphometry showed significant atrophy of grey matter in Alzheimer’s disease patients, especially of both temporal lobes (fusiform and parahippocampal gyri); frontal lobes (posterior cingulate and superior frontal gyri). The study showed correlation between memory impairment and atrophy of memory specific brain regions of frontal and medial temporal lobes. Thus, reduced activation in hippocampal formation and parahippocampal gyri, in posterior cingulate gyrus in patients with Alzheimer's disease correlates to significant atrophy of these regions, detected by voxel-based morphometry, and to deterioration of specific cognitive functions.

Keywords: Alzheimer’s disease, functional MRI, voxel-based morphometry

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Authors: Reva Sharan Thakur, Mrinalini Tiwari, Jyoti das

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Cerebral malaria-associated over expression of pro-inflammatory cytokines and chemokines ultimately results in the up-regulation of adhesion molecules in the brain endothelium leading to sequestration of mature parasitized RBCs in the brain. The high-parasitic load subsequently results in increased mortality or development of neurological symptoms within a week of infection. Studies in the human and experimental cerebral malaria have implicated the breakdown of the integrity of blood-brain barrier during the lethal course of infection, cerebral dysfunction, and fatal organ pathologies that result in multi-organ failure. In the present study, using Plasmodium berghei Anka as a mouse model and in vitro conditions, we have investigated the effect of MSCs to attenuate cerebral malaria pathogenesis by diminishing the effect of inflammation altered organ morphology, reduced parasitemia, and increased survival of the mice. MSCs are also validated for their role in preventing BBB dysfunction and reducing malarial toxins. It was observed that administration of MSCs significantly reduced parasitemia and increased survival in Pb A infected mice. It was further demonstrated that MSCs play a significant role in reversing neurological complexities associated with cerebral malaria. Infusion of MSCs in infected mice decreased hemozoin deposition; oedema, and haemorrhagic lesions in vascular organs. MSCs administration also preserved the integrity of the blood-brain barrier and reduced neural inflammation. Taken together, our results demonstrate the potential of MSCs as an emerging anti-malarial candidate.

Keywords: cerebral malaria, mesenchymal stem cells, erythropoesis, cell death

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Authors: Rahele Mesbah, Nic Van Der Wee, Manja Koenders, Erik Giltay, Albert Van Hemert, Max De Leeuw

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Introduction: Patients with bipolar disorder (BD), characterized by depressive and manic episodes, often suffer from cognitive dysfunction. An up-to-date meta-analysis of functional Magnetic Resonance Imaging (fMRI) studies examining cognitive function in BD is lacking. Objective: The aim of the current fMRI meta-analysis is to investigate brain functioning of bipolar patients compared with healthy subjects within three domains of emotion processing, reward processing, and working memory. Method: Differences in brain regions activation were tested within whole-brain analysis using the activation likelihood estimation (ALE) method. Separate analyses were performed for each cognitive domain. Results: A total of 50 fMRI studies were included: 20 studies used an emotion processing (316 BD and 369 HC) task, 9 studies a reward processing task (215 BD and 213 HC), and 21 studies used a working memory task (503 BD and 445 HC). During emotion processing, BD patients hyperactivated parts of the left amygdala and hippocampus as compared to HC’s, but showed hypoactivation in the inferior frontal gyrus (IFG). Regarding reward processing, BD patients showed hyperactivation in part of the orbitofrontal cortex (OFC). During working memory, BD patients showed increased activity in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Conclusions: This meta-analysis revealed evidence for activity disturbances in several brain areas involved in the cognitive functioning of BD patients. Furthermore, most of the found regions are part of the so-called fronto-limbic network which is hypothesized to be affected as a result of BD candidate genes' expression.

Keywords: cognitive functioning, fMRI analysis, bipolar disorder, fronto-limbic network

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Authors: H. Emari, Z. Emari

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The purpose of this paper is to design an applied framework for strategic thinking which can be applied in all managerial levels and all types of organizational environments. No special applied frame has been presented for this thinking. This paper presents a theoretical framework for the thinking type of a manager by making a historical research and studying the scientific documents about thinking of a strategist. In the new theoretical framework it has been tried to suggest the best type of thinking for a strategist after analyzing the environment of his decisions. So, in this framework, the traditional viewpoint about strategic thinking, which has considered it as a special type of right-brain thinking against other types of right-brain thinking and suggested it for a strategist, was put aside and suggests that the strategist should use a suitable type of thinking under different conditions.

Keywords: strategic thinking, systemic thinking, lateral thinking, intuitive thinking, hybrid thinking

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Authors: Natasha Yasmin Felles, Gerard Riley

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Background and Aims: Relationship breakdown is typical when one partner lives with an acquired brain injury caused by issues like a stroke. Research has found that the perception of relationship satisfaction decreases following such an injury among non-injured partners. Non-injured partners also are found to experience caregiver stress/burden as they immediately have to take the role of a caregiver along with being a partner of the injured. Research has also found that the perception of a continuous relationship, i.e. the perception of the relationship to be essentially the same as it was before the injury, also changes among those caregiving partners. However, there is a lack of available intervention strategies that can help those partners with both individual and relationship difficulties. The aim of this case study was to conduct a pilot test of an intervention aimed to explore whether it is possible to support a partner to experience greater continuity within the relationship poststroke, and what benefits such a change might have. Method: A couple, where one partner experienced an acquired brain injury poststroke were provided with Integrated Behavioural Couples Therapy for 3-months. The intervention addressed goals identified as necessary by the couple and by the formulation of their individual and relationship difficulties, alongside the goal of promoting relationship continuity. Before and after measures were taken using a battery of six questionnaires to evaluate changes in perceptions of continuity, stress, and other aspects of the relationship. Results: Both quantitative and qualitative data showed that relationship continuity was improved after the therapy, as were the measures of stress and other aspects of the relationship. The stress felt by the person with the acquired brain injury also showed some evidence of improvement. Conclusion: The study found that perceptions of relationship continuity can be improved by therapy and that improving these might have a beneficial impact on the stress felt by the carer, their satisfaction with the relationship and overall levels of conflict and closeness within the relationship. The study suggested the value of further research on enhancing perceptions of continuity in the relationship after an acquired brain injury. Currently, the findings of the study have been used to develop a pilot feasibility study to collect substantive evidence on the impact of the intervention on the couples and assess its feasibility and acceptability, which will help in further developing a specific generalized relationship continuity intervention, that will be beneficial in preventing relationship breakdown in the future.

Keywords: acquired brain injury, couples therapy, relationship continuity, stroke

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Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

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In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

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Authors: Mahtab Baghaei, Seyed Mahmoud Tabatabaei

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Aim & Background: Electrical stimulation of transcranial direct current is considered one of the treatment methods for mental disorders. The aim of this study was to evaluate the effectiveness of transcranial electrical stimulation on the delta, theta, alpha, beta and systolic and diastolic blood pressure in patients with generalized anxiety disorder. Materials and Methods: The present study was a double-blind intervention with a pre-test and post-test design on people with generalized anxiety disorder in Tabriz in 1400. In this study, 30 patients with generalized anxiety disorder were selected by purposive sampling method based on the criteria specified in DSM-5 and randomly divided into an experimental group (n = 15) and a control group (n = 15). The experimental group received two sessions of 30 minutes of electrical stimulation of transcranial direct current with an intensity of 2 mA in the area of the lateral dorsal prefrontal cortex, and the control group also received artificial stimulation. Results: The results showed that transcranial electrical stimulation reduces delta and theta waves and increases beta and alpha brain waves in the experimental group. On the other hand, this method also showed a significant decrease in systolic and diastolic blood pressure in these patients (p <0.01). Conclusion: The results show that transcranial electrical stimulation has a statistically significant effect on brain waves and blood pressure, and this non-invasive method can be used as one of the treatment methods in people with generalized anxiety disorder.

Keywords: transcranial direct current electrical stimulation, brain waves, systolic blood pressure, diastolic blood pressure

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Authors: Xiao-Yin Liu, Liang-Xue Zhou

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Traumatic brain injury (TBI), as a kind of nerve trauma caused by an external force, affects people all over the world and is a global public health problem. Although there are various clinical treatments for brain injury, including surgery, drug therapy, and rehabilitation therapy, the therapeutic effect is very limited. To improve the therapeutic effect of TBI, scaffolds combined with exosomes are a promising but challenging method for TBI repair. In this study, we examined whether a novel 3D-printed collagen/chitosan scaffold/exosomes derived from neural stem cells (NSCs) pretreated with insulin growth factor-1 (IGF-I) scaffolds (3D-CC-INExos) could be used to improve TBI repair and functional recovery after TBI. Our results showed that composite scaffolds of collagen-, chitosan- and exosomes derived from NSCs pretreated with IGF-I (INExos) could continuously release the exosomes for two weeks. In the rat TBI model, 3D-CC-INExos scaffold transplantation significantly improved motor and cognitive function after TBI, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that the recovery of damaged nerve tissue in the injured area was significantly improved by 3D-CC-INExos implantation. In conclusion, our data suggest that 3D-CC-INExos might provide a potential strategy for the treatment of TBI and lay a solid foundation for clinical translation.

Keywords: traumatic brain injury, exosomes, insulin growth factor-1, neural stem cells, collagen, chitosan, 3D printing, neural regeneration, angiogenesis, functional recovery

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Authors: Chien-Ho Lin, Ho-Ching Yang, Barbara Knowlton, Shin-Leh Huang, Ming-Chang Chiang

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Practicing motor tasks arranged in an interleaved order (interleaved practice, or IP) generally leads to better learning than practicing tasks in a repetitive order (repetitive practice, or RP), an example of how desirable difficulty during practice benefits learning. Greater difficulty during practice, e.g. IP, is associated with greater brain activity measured by higher blood-oxygen-level dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) in the sensorimotor areas of the brain. In this study resting-state fMRI was applied to investigate whether increase in resting-state brain connectivity immediately after practice predicts the benefit of desirable difficulty to motor learning. 26 healthy adults (11M/15F, age = 23.3±1.3 years) practiced two sets of three sequences arranged in a repetitive or an interleaved order over 2 days, followed by a retention test on Day 5 to evaluate learning. On each practice day, fMRI data were acquired in a resting state after practice. The resting-state fMRI data was decomposed using a group-level spatial independent component analysis (ICA), yielding 9 independent components (IC) matched to the precuneus network, primary visual networks (two ICs, denoted by I and II respectively), sensorimotor networks (two ICs, denoted by I and II respectively), the right and the left frontoparietal networks, occipito-temporal network, and the frontal network. A weighted resting-state functional connectivity (wRSFC) was then defined to incorporate information from within- and between-network brain connectivity. The within-network functional connectivity between a voxel and an IC was gauged by a z-score derived from the Fisher transformation of the IC map. The between-network connectivity was derived from the cross-correlation of time courses across all possible pairs of ICs, leading to a symmetric nc x nc matrix of cross-correlation coefficients, denoted by C = (pᵢⱼ). Here pᵢⱼ is the extremum of cross-correlation between ICs i and j; nc = 9 is the number of ICs. This component-wise cross-correlation matrix C was then projected to the voxel space, with the weights for each voxel set to the z-score that represents the above within-network functional connectivity. The wRSFC map incorporates the global characteristics of brain networks measured by the between-network connectivity, and the spatial information contained in the IC maps measured by the within-network connectivity. Pearson correlation analysis revealed that greater IP-minus-RP difference in wRSFC was positively correlated with the RP-minus-IP difference in the response time on Day 5, particularly in brain regions crucial for motor learning, such as the right dorsolateral prefrontal cortex (DLPFC), and the right premotor and supplementary motor cortices. This indicates that enhanced resting brain connectivity during the early phase of memory consolidation is associated with enhanced learning following interleaved practice, and as such wRSFC could be applied as a biomarker that measures the beneficial effects of desirable difficulty on motor sequence learning.

Keywords: desirable difficulty, functional magnetic resonance imaging, independent component analysis, resting-state networks

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Authors: S. B. R. Slagmulder

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Monitoring inspiratory effort and dynamic lung stress in patients on pressure support ventilation in the ICU is important for protecting against self inflicted lung injury (P-SILI) and diaphragm dysfunction. Strategies to address the detrimental effects of respiratory drive and effort can lead to improved patient outcomes. Two non-invasive estimation methods, occlusion pressure (Pocc) and P0.1, have been proposed for achieving lung and diaphragm protective ventilation. However, their relationship and interpretation in neuro ICU patients is not well understood. P0.1 is the airway pressure measured during a 100-millisecond occlusion of the inspiratory port. It reflects the neural drive from the respiratory centers to the diaphragm and respiratory muscles, indicating the patient's respiratory drive during the initiation of each breath. Occlusion pressure, measured during a brief inspiratory pause against a closed airway, provides information about the inspiratory muscles' strength and the system's total resistance and compliance. Research Objective: Understanding the relationship between Pocc and P0.1 in brain-injured patients can provide insights into the interpretation of these values in pressure support ventilation. This knowledge can contribute to determining extubation readiness and optimizing ventilation strategies to improve patient outcomes. The central goal is to asses a study protocol for determining the relationship between Pocc and P0.1 in brain-injured patients on pressure support ventilation and their ability to predict successful extubation. Additionally, comparing these values between brain-damaged and non-brain-damaged patients may provide valuable insights. Key Areas of Inquiry: 1. How do Pocc and P0.1 values correlate within brain injury patients undergoing pressure support ventilation? 2. To what extent can Pocc and P0.1 values serve as predictive indicators for successful extubation in patients with brain injuries? 3. What differentiates the Pocc and P0.1 values between patients with brain injuries and those without? Methodology: P0.1 and occlusion pressures are standard measurements for pressure support ventilation patients, taken by attending doctors as per protocol. We utilize electronic patient records for existing data. Unpaired T-test will be conducted to compare P0.1 and Pocc values between both study groups. Associations between P0.1 and Pocc and other study variables, such as extubation, will be explored with simple regression and correlation analysis. Depending on how the data evolve, subgroup analysis will be performed for patients with and without extubation failure. Results: While it is anticipated that neuro patients may exhibit high respiratory drive, the linkage between such elevation, quantified by P0.1, and successful extubation remains unknown The analysis will focus on determining the ability of these values to predict successful extubation and their potential impact on ventilation strategies. Conclusion: Further research is pending to fully understand the potential of these indices and their impact on mechanical ventilation in different patient populations and clinical scenarios. Understanding these relationships can aid in determining extubation readiness and tailoring ventilation strategies to improve patient outcomes in this specific patient population. Additionally, it is vital to account for the influence of sedatives, neurological scores, and BMI on respiratory drive and occlusion pressures to ensure a comprehensive analysis.

Keywords: brain damage, diaphragm dysfunction, occlusion pressure, p0.1, respiratory drive

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Authors: Arezou Hajhashemi, Karim Asgari, Masoud Etemadifar, Maryam Keyvani, Ali Hekmatnia

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Multiple Sclerosis (MS) is one of the most prevalent demyelinating diseases in CNS. As in other chronic cerebral diseases, impairment in cognitive functioning and in memory is popular. Because of the inflammatory and demyelinating nature of the disease, the localization of plaques in different parts of the Prefrontal and Limbic System, may lead to memorial symptoms. This investigation was intended to study relationship between frequency of plaques and memorial symptoms arising from dysfunction limbic system and prefrontal of patients with MS. The sample was selected randomly from patients with MS with memory problem, who have been referred to Isfahan Multiple Sclerosis Society. Brain System Test and Memory Test was administered to the sample, and their MRI's were analyzed by specialist in order to indentify two different parts of plaques. The data was analyzed by SPSS. The results showed that there were significant relationship between MS plaques and prefrontal's dysfunction and memorial symptom related to prefrontal area; however, there were no significant relationship between MS plaques and limbic system's dysfunction and memorial symptoms related to limbic system area. The results of this study suggest that memorial symptoms due to injury regions of the brain have the most significant relationship to prefrontal. Better judgment about these results needs more studies in future.

Keywords: multiple sclerosis, magnetic image, brain injury, behavior disorder

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Authors: Ranjeet Kumar, Pravin Suryakantrao Deshmukh, Sonal Sharma, Basudev Banerjee

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With the tremendous increase in exposure to radiofrequency microwaves emitted by mobile phones, globally public awareness has grown with regard to the potential health hazards of microwaves on the nervous system in the brain. India alone has more than one billion mobile users out of 4.3 billion globally. Our studies have suggested that radio frequency able to affect neuronal alterations in the brain, and hence, affecting cognitive behaviour. However, adverse effect of low-intensity microwave exposure with endoplasmic reticulum stress and autophagy has not been evaluated yet. In this study, we explore whether low-intensity microwave induces endoplasmic reticulum stress and autophagy with varying frequency and time duration in Wistar rat. Ninety-six male Wistar rat were divided into 12 groups of 8 rats each. We studied at 900 MHz, 1800 MHz, and 2450 MHz frequency with reference to sham-exposed group. At the end of the exposure, the rats were sacrificed to collect brain tissue and expression of CHOP, ATF-4, XBP-1, Bcl-2, Bax, LC3 and Atg-4 gene was analysed by real-time PCR. Significant fold change (p < 0.05) of gene expression was found in all groups of 1800 MHz and 2450 MHz exposure group in comparison to sham exposure group. In conclusion, the microwave exposure able to induce ER stress and modulate autophagy. ER (endoplasmic reticulum) stress and autophagy vary with increasing frequency as well as the duration of exposure. Our results suggested that microwave exposure is harmful to neuronal health as it induces ER stress and hampers autophagy in neuron cells and thereby increasing the neuron degeneration which impairs cognitive behaviour of experimental animals.

Keywords: autophagy, ER stress, microwave, nervous system, rat

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Authors: S. H. Jang

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Posterior reversible encephalopathy syndrome (PRES) is characterized by acute neurologic symptoms (visual loss, headache, altered mentality and seizures) and by typical imaging findings (bilateral subcortical and cortical edema with predominatly posterior distribution). Nephrotic syndrome is a syndrome comprising signs of proteinuria, hypoalbuminemia, and edema. It is well known that hypertension predispose patient with nephrotic syndrome to PRES. A 45-year old male was referred for suddenly developed vertigo, disequilibrium. He had previous history of nephrotic syndrome. His medical history included diabetes controlled with medication. He was hospitalized because of generalized edema a few days ago. His vital signs were stable. On neurologic examination, his mental state was alert. Horizontal nystagmus to right side on return to primary position was observed. He showed good grade motor weakness and ataxia in right upper and lower limbs without other sensory abnormality. Brain MRI showed increased signal intensity in FLAIR image, decreased signal intensity in T1 image and focal enhanced lesion in T1 contrast image at whole midbrain, pons and cerebellar peduncle symmetrically, which was compatible with vasogenic edema. Laboratory findings showed severe proteinuria and hypoalbuminemia. He was given intravenous dexamethasone and diuretics to reduce vasogenic edema and raise the intra-vascular osmotic pressure. Nystagmus, motor weakness and limb ataxia improved gradually over 2 weeks; He recovered without any neurologic symptom and sign. Follow-up MRI showed decreased vasogenic edema fairly. We report a case of brain stem PRES in normotensive, nephrotic syndrome patient.

Keywords: posterior reversible encephalopathy syndrome, MRI, nephrotic syndrome, vasogenic brain edema

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Authors: Hsiao-Wen Tsai

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Motor vehicle accident is the first cause of head injury in the world; severe head injury cases may cause conscious disturbance and death. This is a report about a case of a young adult patient suffering from motor vehicle accident leading to severe head injury who passed through three time surgical procedures, and his mother (who is the informal caregiver). This case was followed from 28th January to 15th February 2011 by using Gordon’s 11 functional health patterns. Patient’s cognitive-perceptual and self-perception-self-concept patterns were altered. Anxiety was also noted on his informal caregiver due to patients’ condition. During the intensive care period, maintaining patient’s vital signs and cerebral perfusion pressure were essential to avoid secondary neuronal injury. Multi-sensory stimulation, caring accompanying, supporting, listening and encouraging patient’s family involved in patient care were very important to reduce informal caregiver anxiety. Finally, the patient consciousness improved from GCS 4 to GCS 11 before discharging from ICU. Patient’s primary informal caregiver, his mother, also showed anxiety improvement. This is was successful case with traumatic brain injury recovered from coma.

Keywords: anxiety, multi-sensory stimulation, reduce intracranial adaptive capacity, traumatic brain injury

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Authors: Zenah Gheblawi, Susan Armijo-Olivo, Elisa B. Pelai, Vaishali Sharma, Musa Tashfeen, Angela Fung, Francisca Claveria

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Due to physiological differences between men and women, pain is experienced differently between the two sexes. Chronic pain disorders, notably temporomandibular disorders (TMDs), disproportionately affect women in diagnosis, and pain severity in opposition of their male counterparts. TMDs are a type of musculoskeletal disorder that target the masticatory muscles, temporalis muscle, and temporomandibular joints, causing considerable orofacial pain which can usually be referred to the neck and back. Therapeutic methods are scarce, and are not TMD-centered, with the latest research suggesting that subjects with chronic musculoskeletal pain disorders have abnormal alterations in the grey matter of their brains which can be remedied with exercise, and thus, decreasing the pain experienced. The aim of the study is to investigate the effects of exercise therapy in TMD female patients experiencing chronic jaw pain and to assess the consequential effects on brain activity. In a randomized controlled trial, the effectiveness of an exercise program to improve brain alterations and clinical outcomes in women with TMD pain will be tested. Women with chronic TMD pain will be randomized to either an intervention arm or a placebo control group. Women in the intervention arm will receive 8 weeks of progressive exercise of motor control training using visual feedback (MCTF) of the cervical muscles, twice per week. Women in the placebo arm will receive innocuous transcutaneous electrical nerve stimulation during 8 weeks as well. The primary outcomes will be changes in 1) pain, measured with the Visual Analogue Scale, 2) brain structure and networks, measured by fractional anisotropy (brain structure) and the blood-oxygen level dependent signal (brain networks). Outcomes will be measured at baseline, after 8 weeks of treatment, and 4 months after treatment ends and will determine effectiveness of MCTF in managing TMD, through improved clinical outcomes. Results will directly inform and guide clinicians in prescribing more effective interventions for women with TMD. This study is underway, and no results are available at this point. The results of this study will have substantial implications on the advancement in understanding the scope of plasticity the brain has in regards with pain, and how it can be used to improve the treatment and pain of women with TMD, and more generally, other musculoskeletal disorders.

Keywords: exercise therapy, musculoskeletal disorders, physical therapy, rehabilitation, tempomandibular disorders

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Authors: M. E. Kolpakova, A. A. Jakovleva, L. S. Poliakova, H. El Amghari, S. Soliman, D. R. Faizullina, V. V. Sharoyko

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Brain neuroplasticity is associated with blood-brain barrier vascular endothelial proteoglycans and post-stroke microglial activation. The study of the mechanisms of reperfusion injury limitation by remote ischemic postconditioning (RC) is of interest due to the effects on functional recovery after cerebral ischemia. The goal of the study is the assessment of the role of syndecan-1 (SDC-1) in restriction of ischemic-reperfusion injury on middle cerebral artery model in rats using RC protocol. Randomized controlled trials were conducted. Ischemia was performed by middle cerebral artery occlusion by Belayev L. (1996) on the Wistar rat-males (n= 87) weighting 250 ± 50 g. under general anesthesia (Zoletil 100 и Xylazine 2%). Syndecan-1 (SDC-1) concentration difference in plasma samples of false operated animals and animals with brain ischemia was 30% (30 min. МСАо: 41.4 * ± 1.3 ng/ml). SDC-1 concentration in animal plasma samples with ischemia + RC protocol was 112% (30 min МСАо+ RC): 67.8**± 5.8 ng/ml). Calculation of infarction volume in the ischemia group revealed brain injury in 31.97 ± 2.5%; the volume of infarction was 13.6 ± 1.3% in 30 min. МCАо + RC group. Swelling of tissue in the group 30 min. МCАо + RC was 16 ± 2.1%; it was 47 ± 3.3%. in 30 min. МCАо group. Correlation analysis showed a high direct correlation relationship between infarct area and muscle strength in the right forelimb (КК=0.72) in the 30 min. МCАо + RC group. Correlation analysis showed very high inverse correlation between infarct area and capillary blood flow in the 30 min. МCАо + RC group (p <0.01; r = -0.98). We believe the SDC-1 molecule in blood plasma may play role of potential messenger of ischemic-reperfusion injury restriction mechanisms. This leads to infarct-limiting effect of remote ischemic postconditioning and early functioning recovery.

Keywords: ischemia, МСАо, remote ischemic postconditioning, syndecan-1

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Authors: Caroline Kim

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Scholars have long disputed the relationship between the origins of language and human behavior. Historically, behaviorist psychologist B. F. Skinner argued that language is one instance of the general stimulus-response phenomenon that characterizes the essence of human behavior. Another, more recent approach argues, by contrast, that language is an innate cognitive faculty and does not arise from behavior, which might develop and reinforce linguistic facility but is not its source. Pinker, among others, proposes that linguistic defects arise from damage to the brain, both congenital and acquired in life. Much of his argument is based on case studies in which damage to the Broca’s and Wernicke’s areas of the brain results in loss of the ability to produce coherent grammatical expressions when speaking or writing; though affected speakers often utter quite fluent streams of sentences, the words articulated lack discernible semantic content. Pinker concludes on this basis that language is an innate component of specific, classically language-correlated regions of the human brain. Taking a notorious 1970s case of linguistic maladaptation, this paper queries the dominant materialist paradigm of language-correlated regions. Susan “Genie” Wiley was physically isolated from language interaction in her home and beaten by her father when she attempted to make any sort of sound. Though without any measurable resulting damage to the brain, Wiley was never able to develop the level of linguistic facility normally achieved in adulthood. Having received a negative reinforcement of language acquisition from her father and lacking the usual language acquisition period, in adulthood Wiley was able to develop language only at a quite limited level in later life. From a contemporary behaviorist perspective, this case confirms the possibility of language deficiency without brain pathology. Wiley’s potential language-determining areas in the brain were intact, and she was exposed to language later in her life, but she was unable to achieve the normal level of communication skills, deterring socialization. This phenomenon and others like it in the case limited literature on linguistic maladaptation pose serious clinical, scientific, and indeed philosophical difficulties for both of the major competing theories of language acquisition, innateness, and linguistic stimulus-response. The implications of such cases for future research in language acquisition are explored, with a particular emphasis on the interaction of innate capacity and stimulus-based development in early childhood.

Keywords: behaviorism, innateness hypothesis, language, Susan "Genie" Wiley

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Authors: Elif Unveren, Ozlem Bozkurt

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Emotion processing happens when someone has a negative, stressful experience and gets over it in time, and it is a different experience for every person. As to look into emotion processing can be categorised by intensity, awareness, coordination, speed, accuracy and response. It may vary depending on people’s age, sex and conditions. Each emotion processing shows different activation patterns in different brain regions. Activation is significantly higher in the right frontal areas. The highest activation happens in extended frontotemporal areas during the processing of happiness, sadness and disgust. Those emotions also show widely disturbed differences and get produced earlier than anger and fear. For different occasions, listed variables may have less or more importance. A borderline personality disorder is a condition that creates an unstable personality, sudden mood swings and unpredictability of actions. According to a study that was made with healthy people and people who had BPD, there were significant differences in some categories of emotion processing, such as intensity, awareness and accuracy. According to another study that was made to show the emotional processing differences between puberty and was made for only females who were between the ages of 11 and 17, it was perceived that for different ages and hormone levels, different parts of the brain are used to understand the given task. Also, in the different study that was made for kids that were between the age of 4 and 15, it was observed that the older kids were processing emotion more intensely and expressing it to a greater extent. There was a significant increase in fear and disgust in those matters. To sum up, we can say that the activity of undertaking negative experiences is a unique thing for everybody for many different reasons.

Keywords: age, sex, conditions, brain regions, emotion processing

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Authors: Hashem Al Argha

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Cerebral Aneurysms are the ballooning and defect that occurs in the arteries of the brain. This ballooning might enlarge in size due to mechanical forces and could lead to rupture and death. Computational Fluid Dynamics has been used in the recent years in creating a link between engineering sciences and medical sciences. In this paper, the effects of mechanical forces on cerebral aneurysms will be studied. Results of this study show that mechanical forces could lead to rupture of the aneurysm and could lead to death. High mechanical forces including stresses up to 1.7 MPa could pop aneurysms and lead to a brain hemorrhage.

Keywords: computational fluid dynamics, numerical, aneurysm, mechanical forces

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Authors: B. Shukir, L. Szivos, D. Kis, P. Barzo

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Glioblastoma is the most malignant brain tumor. In general, the survival rate varies between (14-18) months. Glioblastoma consists a solid and infiltrative part. The standard therapeutic management of glioblastoma is maximum safe resection followed by chemo-radiotherapy. It’s hypothesized that the pretumoral hyperintense region in fluid attenuated inversion recovery (FLAIR) images includes both vasogenic edema and infiltrated tumor cells. In our study, we aimed to define the sensitivity and specificity of hyperintense FLAIR images preoperatively to examine how well it can define the true extent of glioblastoma. (16) glioblastoma patients included in this study. Hyperintense FLAIR region were delineated preoperatively as tumor mask. The infiltrative part of glioblastoma considered the regions where the tumor recurred on the follow up MRI. The recurrence on the CE-T1 images was marked as the recurrence masks. According to (AAL3) and (JHU white matter labels) atlas, the brain divided into cortical and subcortical regions respectively. For calculating specificity and sensitivity, the FLAIR and the recurrence masks overlapped counting how many regions affected by both . The average sensitivity and specificity was 83% and 85% respectively. Individually, the sensitivity and specificity varied between (31-100)%, and (100-58)% respectively. These results suggest that despite FLAIR being as an effective radiologic imaging tool its prognostic value remains controversial and probabilistic tractography remain more reliable available method for identifying the true extent of glioblastoma.

Keywords: brain tumors, glioblastoma, MRI, FLAIR

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Authors: Salma A. El-Marasy, Reham M. Abd-Elsalam, Omar A. Ahmed-Farid

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Dementia is characterized by impairments in memory and other cognitive abilities. This study aims to elucidate the possible ameliorative effect of silymarin on scopolamine-induced dementia using the object recognition test (ORT). The study was extended to demonstrate the role of cholinergic activity, oxidative stress, neuroinflammation, brain neurotransmitters and histopathological changes in the anti-amnestic effect of silymarin in demented rats. Wistar rats were pretreated with silymarin (200, 400, 800 mg/kg) or donepezil (10 mg/kg) orally for 14 consecutive days. Dementia was induced after the last drug administration by a single intraperitoneal dose of scopolamine (16 mg/kg). Then behavioral, biochemical, histopathological, and immunohistochemical analyses were then performed. Rats pretreated with silymarin counteracted scopolamine-induced non-spatial working memory impairment in the ORT and decreased acetylcholinesterase (AChE) activity, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), restored gamma-aminobutyric acid (GABA) and dopamine (DA) contents in the cortical and hippocampal brain homogenates. Silymarin dose-dependently reversed scopolamine-induced histopathological changes. Immunohistochemical analysis showed that silymarin dose-dependently mitigated protein expression of a glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NF-κB) in the brain cortex and hippocampus. All these effects of silymarin were similar to that of the standard anti-amnestic drug, donepezil. This study reveals that the ameliorative effect of silymarin on scopolamine-induced dementia in rats using the ORT maybe in part mediated by, enhancement of cholinergic activity, anti-oxidant and anti-inflammatory activities as well as mitigation in brain neurotransmitters and histopathological changes.

Keywords: dementia, donepezil, object recognition test, rats, silymarin, scopolamine

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Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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Authors: Panda Krouse

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This work is a marriage of the science of Applied Behavioral Analysis and an educator’s look at Neuroscience. The focus is integrating what we know about the anatomy of the brain in autism and evidence-based practices in education. It is a bold attempt to present links between neurological research and the application of evidence-based practices in education. In researching for this work, no discovery of articles making these connections was made. Consideration of the areas of structural differences in the brain are aligned with evidence-based strategies. A brief literary review identifies how identified areas affect overt behavior, which is what, as educators, is what we can see and measure. Giving further justification and validation of our practices in education from a second scientific field is significant for continued improvement in intervention for students on the autism spectrum.

Keywords: autism, evidence based practices, neurological differences, education intervention

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Authors: Bayar Shahab

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The fast development of technology that has advanced neuroscience and human interaction with computers has enabled solutions to various problems, and issues of this new era have been found and are being found like no other time in history. Brain-computer interface so-called BCI has opened the door to several new research areas and have been able to provide solutions to critical and important issues such as supporting a paralyzed patient to interact with the outside world, controlling a robot arm, playing games in VR with the brain, driving a wheelchair or even a car and neurotechnology enabled the rehabilitation of the lost memory, etc. This review work presents state-of-the-art methods and improvements of canonical correlation analyses (CCA), which is an SSVEP-based BCI method. These are the methods used to extract EEG signal features or, to be said in a different way, the features of interest that we are looking for in the EEG analyses. Each of the methods from oldest to newest has been discussed while comparing their advantages and disadvantages. This would create a great context and help researchers to understand the most state-of-the-art methods available in this field with their pros and cons, along with their mathematical representations and usage. This work makes a vital contribution to the existing field of study. It differs from other similar recently published works by providing the following: (1) stating most of the prominent methods used in this field in a hierarchical way (2) explaining pros and cons of each method and their performance (3) presenting the gaps that exist at the end of each method that can open the understanding and doors to new research and/or improvements.

Keywords: BCI, CCA, SSVEP, EEG

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Authors: Luc de Brabandere

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Searchers in various disciplines have long tried to understand how a human being thinks. Most of them seem to agree that the brain works in two very different modes. For us, the first phase of thought imagines, diverges, and unlocks the field of possibilities. The second phase, judges converge and choose. But if we were to stop there, that would give the impression that thought is essentially an individual effort that seldom depends on context. This is, however, not the case. Whether we be a champion in creativity, so primarily in induction, or a master in logic where we are confronted with reality, the ideas we layout are indeed destined to be presented to third parties. They should therefore be exposed, defended, communicated, negotiated, or even sold. Regardless of the quality of the concepts we craft (creative thinking) and the interferences we build (logical thinking) we will take one day, or another, be confronted by people whose beliefs, opinions and ideas differ from ours (critical thinking). Logic and critique: The shared characteristics of logical and critical thoughts include a three-level structure of reasoning invented by the Greeks. For the first time in history, Aristotle tried to model thought deployable in three stages: the concept, the statement, and the reasoning. The three levels can be assessed according to different criteria. A concept is more or less useful, a statement is true or false, and reasoning is right or wrong. This three-level structure allows us to differentiate logic and critique, where the intention and words used are not the same. Logic only deals with the structure of reasoning and exhausts the problem. It regards premises as acquired and excludes the debate. Logic is in all certainty and pursues the truth. Critique is most probably searching for the plausible. Logic and creativity: Many known models present the brain as a two-stroke engine (divergence vs convergence, fast vs. slow, left-brain vs right-brain, Yin vs Yang, etc.). But that’s not the only thing. “Why didn’t we think of that before?” How often have we heard that sentence? A creative idea is the outcome of logic, but you can only understand it afterward! Through the use of exercises, we will witness how logic and creativity work together. A third theme is hidden behind the two main themes of the conference: logical thought, which the author can shed some light on.

Keywords: creativity, logic, critique, digital

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Authors: Janneth Gonzalez, Marco Avila, George Barreto

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GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and unfolded protein response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and heat shock proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and molecular dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.

Keywords: computational biology, protein interactions, Grp78, bioinformatics, molecular dynamics

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Authors: Mohamed Mounir Tellache, Hiroyuki Kambara, Yasuharu Koike, Makoto Miyakoshi, Natsue Yoshimura

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This study explores the practicality of using electroencephalographic (EEG) independent components to predict eight-direction finger movements in pseudo-real-time. Six healthy participants with individual-head MRI images performed finger movements in eight directions with two different arm configurations. The analysis was performed in two stages. The first stage consisted of using independent component analysis (ICA) to separate the signals representing brain activity from non-brain activity signals and to obtain the unmixing matrix. The resulting independent components (ICs) were checked, and those reflecting brain-activity were selected. Finally, the time series of the selected ICs were used to predict eight finger-movement directions using Sparse Logistic Regression (SLR). The second stage consisted of using the previously obtained unmixing matrix, the selected ICs, and the model obtained by applying SLR to classify a different EEG dataset. This method was applied to two different settings, namely the single-participant level and the group-level. For the single-participant level, the EEG dataset used in the first stage and the EEG dataset used in the second stage originated from the same participant. For the group-level, the EEG datasets used in the first stage were constructed by temporally concatenating each combination without repetition of the EEG datasets of five participants out of six, whereas the EEG dataset used in the second stage originated from the remaining participants. The average test classification results across datasets (mean ± S.D.) were 38.62 ± 8.36% for the single-participant, which was significantly higher than the chance level (12.50 ± 0.01%), and 27.26 ± 4.39% for the group-level which was also significantly higher than the chance level (12.49% ± 0.01%). The classification accuracy within [–45°, 45°] of the true direction is 70.03 ± 8.14% for single-participant and 62.63 ± 6.07% for group-level which may be promising for some real-life applications. Clustering and contribution analyses further revealed the brain regions involved in finger movement and the temporal aspect of their contribution to the classification. These results showed the possibility of using the ICA-based method in combination with other methods to build a real-time system to control prostheses.

Keywords: brain-computer interface, electroencephalography, finger motion decoding, independent component analysis, pseudo real-time motion decoding

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Authors: Winncy Du, Jeremy Nguyen, Harpinder Dhillon, Reinardus Justin Halim, Clayton Haske, Trent Hughes, Marissa Ortiz, Rozy Saini

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Stroke often causes death or cerebro-vascular (CV) brain damage. Most patients with CV brain damage lost their motor control on their limbs. This paper focuses on developing a reliable, safe, and non-invasive EEG-based robot-assistant stroke rehabilitation system to help stroke survivors to rapidly restore their motor control functions for their limbs. An electroencephalogram (EEG) recording device (EPOC Headset) and was used to detect a patient’s brain activities. The EEG signals were then processed, classified, and interpreted to the motion intentions, and then converted to a series of robot motion commands. A six-axis articulated robot (AdeptSix 300) was employed to provide the intended motions based on these commends. To ensure the EEG device, the computer, and the robot can communicate to each other, an Arduino microcontroller is used to physically execute the programming codes to a series output pins’ status (HIGH or LOW). Then these “hardware” commends were sent to a 24 V relay to trigger the robot’s motion. A lookup table for various motion intensions and the associated EEG signal patterns were created (through training) and installed in the microcontroller. Thus, the motion intention can be direct determined by comparing the EEG patterns obtaibed from the patient with the look-up table’s EEG patterns; and the corresponding motion commends are sent to the robot to provide the intended motion without going through feature extraction and interpretation each time (a time-consuming process). For safety sake, an extender was designed and attached to the robot’s end effector to ensure the patient is beyond the robot’s workspace. The gripper is also designed to hold the patient’s limb. The test results of this rehabilitation system show that it can accurately interpret the patient’s motion intension and move the patient’s arm to the intended position.

Keywords: brain waves, EEG sensor, motion control, robot-assistant stroke rehabilitation

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Authors: Azza A. Ali, Asmaa Abdelaty, Mona G. Khalil, Mona M. Kamal, Karema Abu-Elfotuh

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Background: Aluminium (Al) is known as a neurotoxin environmental pollutant that can cause certain diseases as Dementia, Alzheimer's disease, and Parkinsonism. It is widely used in antacid drugs as well as in food additives and toothpaste. Stresses have been linked to cognitive impairment; Social isolation (SI) may exacerbate memory deficits while protein malnutrition (PM) increases oxidative damage in cortex, hippocampus and cerebellum. The risk of cognitive decline may be lower by maintaining social connections. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and has antioxidant, anti-inflammatory and anti-atherogenic effects as well as health-promoting effects in CNS. Objective: To study the influence of different stressful conditions as social isolation, electric shock (EC) and inadequate Nutritional condition as PM on neurotoxicity induced by Al in rats as well as to investigate the possible protective effect of EGCG in these stressful and PM conditions. Methods: Rats were divided into two major groups; protected group which was daily treated during three weeks of the experiment by EGCG (10 mg/kg, IP) or non-treated. Protected and non-protected groups included five subgroups as following: One normal control received saline and four Al toxicity groups injected daily for three weeks by ALCl3 (70 mg/kg, IP). One of them served as Al toxicity model, two groups subjected to different stresses either by isolation as mild stressful condition (SI-associated Al toxicity model) or by electric shock as high stressful condition (EC- associated Al toxicity model). The last was maintained on 10% casein diet (PM -associated Al toxicity model). Isolated rats were housed individually in cages covered with black plastic. Biochemical changes in the brain as acetyl cholinesterase (ACHE), Aβ, brain derived neurotrophic factor (BDNF), inflammatory mediators (TNF-α, IL-1β), oxidative parameters (MDA, SOD, TAC) were estimated for all groups. Histopathological changes in different brain regions were also evaluated. Results: Rats exposed to Al for three weeks showed brain neurotoxicity and neuronal degenerations. Both mild (SI) and high (EC) stressful conditions as well as inadequate nutrition (PM) enhanced Al-induced neurotoxicity and brain neuronal degenerations; the enhancement induced by stresses especially in its higher conditions (ES) was more pronounced than that of inadequate nutritional conditions (PM) as indicated by the significant increase in Aβ, ACHE, MDA, TNF-α, IL-1β together with the significant decrease in SOD, TAC, BDNF. On the other hand, EGCG showed more pronounced protection against hazards of Al in both stressful conditions (SI and EC) rather than in PM .The protective effects of EGCG were indicated by the significant decrease in Aβ, ACHE, MDA, TNF-α, IL-1β together with the increase in SOD, TAC, BDNF and confirmed by brain histopathological examinations. Conclusion: Neurotoxicity and brain neuronal degenerations induced by Al were more severe with stresses than with PM. EGCG can protect against Al-induced brain neuronal degenerations in all conditions. Consequently, administration of EGCG together with socialization as well as adequate protein nutrition is advised especially on excessive Al-exposure to avoid the severity of its neuronal toxicity.

Keywords: environmental pollution, aluminum, social isolation, protein malnutrition, neuronal degeneration, epigallocatechin-3-gallate, rats

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