Neuronal Activity In Brain Research Articles

Estimating hemodynamic stimulus and blood vessel compliance from cerebral blood flow data

Several key brain imaging modalities that are intended for retrieving information about neuronal activity in brain, the BOLD fMRI as a foremost example, rely on the assumption that elevated neuronal activity elicits spatiotemporally well localized increase of the oxygenated blood volume, which in turn can be monitored non-invasively. The details of the signaling in the neurovascular unit during hyperemia are still not completely understood, and remain a topic of active research, requiring good mathematical models that are able to couple the different aspects of the signaling event. In this work, the question of estimating the hemodynamic stimulus function from cerebral blood flow data is addressed. In the present model, the hemodynamic stimulus is a non-specific signal from the electrophysiological and metabolic complex that controls the compliance of the blood vessels, leading to a vasodilation and thereby to an increase of blood flow. The underlying model is based on earlier literature, and it is further developed in this article for the needs of the inverse problem, which is solved using hierarchical Bayesian methodology, addressing also the poorly known model parameters.

Molecular Mechanisms of the Effects of Metformin on the Functional Activity of Brain Neurons

Metformin (MF) is the most widely used drug for the treatment of type 2 diabetes mellitus and metabolic syndrome (MS). In the peripheral tissues, MF inhibits mitochondrial respiratory chain complex I and increases the activity of AMP-activated protein kinase (AMPK), leading to suppression of gluconeogenesis in the liver, increased insulin sensitivity, increased glucose utilization, and normalization of lipid metabolism. Recent years have seen the appearance of experimental and clinical evidence showing that the CNS is also a major target of MF, such that the action of MF on the functional state of neurons can be mediated both via AMPK-dependent and via AMPK-independent signal cascades. In contrast to the periphery, MF does not activate but suppresses AMPK activity in hypothalamic neurons, this influencing the ratio of anorexigenic (melanocortin peptides) and orexigenic (neuropeptide Y) factors and altering feeding behavior. A significant contribution to this effect is made by MF-induced activation of the leptin-dependent STAT3 signal cascade. As the leptin and melanocortin systems targeted by MF interact closely with the insulin and monoamine systems, MF, acting through them, affects the entire integrative signal system of the brain, on which the functioning of the nervous, endocrine, cardiovascular, and other body systems depend. This review analyzes and systematizes data on the molecular mechanisms and targets of the action of MF in brain neurons, and the effects of this drug, which are mediated or may be mediated by the interactions of MF with the CNS.

Serotonin2B receptors in the rat dorsal raphe nucleus exert a GABA-mediated tonic inhibitory control on serotonin neurons

The central serotonin2B receptor (5-HT2BR) is a well-established modulator of dopamine (DA) neuron activity in the rodent brain. Recent studies in rats have shown that the effect of 5-HT2BR antagonists on accumbal and medial prefrontal cortex (mPFC) DA outflow results from a primary action in the dorsal raphe nucleus (DRN), where they activate 5-HT neurons innervating the mPFC. Although the mechanisms underlying this interaction remain largely unknown, data in the literature suggest the involvement of DRN GABAergic interneurons in the control of 5-HT activity. The present study examined this hypothesis using in vivo (intracerebral microdialysis) and in vitro (immunohistochemistry coupled to reverse transcription-polymerase chain reaction) experimental approaches in rats. Intraperitoneal (0.16 mg/kg) or intra-DRN (1 μM) administration of the selective 5-HT2BR antagonist RS 127445 increased 5-HT outflow in both the DRN and the mPFC, these effects being prevented by the intra-DRN perfusion of the GABAA antagonist bicuculline (100 μM), as well as by the subcutaneous (0.16 mg/kg) or the intra-DRN (0.1 μM) administration of the selective 5-HT1AR antagonist WAY 100635. The increase in DRN 5-HT outflow induced by the intra-DRN administration of the selective 5-HT reuptake inhibitor citalopram (0.1 μM) was potentiated by the intra-DRN administration (0.5 μM) of RS 127445 only in the absence of bicuculline perfusion. Finally, in vitro experiments revealed the presence of the 5-HT2BR mRNA on DRN GABAergic interneurons. Altogether, these results show that, in the rat DRN, 5-HT2BRs are located on GABAergic interneurons, and exert a tonic inhibitory control on 5-HT neurons innervating the mPFC.

Abstract 077: Captopril-Induced Sustained Reduction in Blood Pressure is Associated With Alterations in Gut-Brain Axis in the Spontaneously Hypertensive Rats

Objective: The anti-hypertensive effect of captopril (CAP) is prolonged even when the treatment is discotinued. Our recent findings indicate the beneficial effect of CAP on hypertension-linked gut pathology. Given the roles of brain and gut/microbiota in hypertension, we hypothesized that prolonged anti-hypertensive effect of CAP is through impacts on the brain-gut axis. Accordingly, we tested if CAP induced alterations in the brain and the gut, and if the changes are preserved in the SHR following CAP withdrawal. Methods: Male SHR and normotensive Wistar Kyoto (WKY) rats were treated with CAP (250mg/kg/day) in water for 4 weeks followed by its withdrawal for 16 weeks (weeks 5-20). Systolic BP was measured by tailcuff at weeks 3, 5, and 9. Fecal microbiota was analyzed at week 4 and week 8. Brain neuronal activity was measured by manganese-enhanced MRI (MEMRI) at weeks 4 and 8. Gut pathology was assessed at week 20. Results: Unweighted principal coordinate analysis showed that CAP treatment significantly altered gut microbial composition, characterized by separate clusters between untreated and 4 weeks CAP-treated SHR. The composition change was preserved 4 weeks post-withdrawal of CAP. Sustained improvement in fibrotic area (untreated: 12.98±0.81% vs week 20: 10.23±0.69%, P=0.036), goblet cell number (untreated: 39±3.57 cells/villi vs week 20: 65±5.29 cells/villi, P=0.0006), and villi length (untreated: 271.4±9.85 μm vs week 20: 388.8±12.29 μm, P<0.0001) was observed at week 20 compared with untreated SHR. MEMRI demonstrated sustained decrease in neuronal activity in autonomic brain regions, with the most pronounced decrease in the posterior pituitary area in SHR treated with CAP (week 4) and withdrawal of CAP (week 8), compared with untreated control (untreated: 1.57±0.11 vs week 4: 1.14±0.074 vs week 8: 1.05±0.14, P=0.0162). In contrast, CAP-treated WKY showed little change in BP, gut pathology or neuronal activity, but distinct changes in gut microbiota. Conclusion: Oral CAP persistently lowered BP, altered gut microbiota, improved gut pathology and reduced posterior pituitary neuronal activity in the SHR even post-withdrawal of CAP, indicating persistent antihypertensive effect of CAP may result from altered brain-gut communication.

Single unit activity of subthalamic nucleus of patients with Parkinson’s disease under local and generalized anaesthesia: Multifactor analysis

The analysis of neuronal activity in human brain is a complicated task as it meets several limitations, including small sample sizes, dependent variables in the dataset and the short duration of recordings that entangles the analysis procedure. Here, we present the comparative research of neuronal activity in subthalamic nucleus (STN) of 8 Parkinsonian patients undergoing DBS surgery in awake state and under propofol anaesthesia using different statistical approaches. We studied 25 parameters of single unit activity and performed a direct comparison of the parameters between the groups to characterise the changes in STN activity under anaesthesia. We found a significant decrease in firing rate and a prominent increase in bursting of neurons in the anaesthetised state. Also, these data were used to determine the most important parameters for classification. We revealed the differences between parametric and nonparametric approaches regarding the identification of the most important spike train features. The random forest trees algorithm showed a greater accuracy of classification (91.7 ± 1.8%) compared to generalised linear models (82.4 ± 3.8%). The lists of the features important for classification according to F-scores and random forest trees also differed markedly. Our results indicate that feature interactions play a key role in neuronal activity analysis and must be taken into account.

Advances in Nanomaterials for Brain Microscopy.

Microscopic imaging of the brain continues to reveal details of its structure, connectivity, and function. To further improve our understanding of the emergent properties and functions of neural circuits, new methods are necessary to directly visualize the relationship between brain structure, neuron activity, and neurochemistry. Advances in engineering the chemical and optical properties of nanomaterials concurrent with developments in deep-tissue microscopy hold tremendous promise for overcoming the current challenges associated with in vivo brain imaging, particularly for imaging the brain through optically-dense brain tissue, skull, and scalp. To this end, developments in nanomaterials offer much promise toward implementing tunable chemical functionality for neurochemical targeting and sensing, and fluorescence stability for long-term imaging. In this review, we summarize current brain microscopy methods and describe the diverse classes of nanomaterials recently leveraged as contrast agents and functional probes for microscopic optical imaging of the brain.

Characterization of sickness behavior in zebrafish

In a previous study we showed a clear relationship between immune system and behavior in zebrafish and we hypothesized that the immune system is capable of inducing behavioral changes. To further investigate this subject and to address our main question, here we induced an inflammatory response in one group of fish by the inoculation of formalin-inactivated Aeromonoas hydrophila bacterin and compared their social and exploratory behavior with control groups. After the behavioral tests, we also analyzed the expression of cytokines genes and markers of neuronal activity in fish brain. In the bacterin-inoculated fish, the locomotor activity, social preference and exploratory behavior towards a new object were reduced compared to the control fish while the expression of proinflammatory cytokines in the brain was upregulated. With this study we demonstrated for the first time that the immune system is capable of causing behavioral changes that are consistent with the sickness behavior observed in mammals.

Altered Fractional Amplitude of Low Frequency Fluctuations in Unmedicated Female Patients with Obsessive-Compulsive Disorder.

A number of resting-state functional magnetic resonance imaging (rs-fMRI) studies indicate dysfunction of large-scale brain networks underlying the pathophysiology of obsessive-compulsive disorder (OCD). Recent epidemiology studies show that the prevalence of female OCD patients is higher than that of males. However, the underlying neurobiology mechanism for female OCD patients remains not fully understood. In this study, we are aimed to explore the spontaneous brain neuronal activity in unmedicated female OCD patients using rs-fMRI methodology and fractional amplitude of low frequency fluctuations (fALFF) analysis. Additionally, we examine the relationship between fALFF changes and female OCD symptomatology. Increased fALFF values in right brainstem, right rectus, left middle temporal gyrus and right angular were found in OCD females. And decreased fALFF values in right cerebellum, left middle occipital gyrus, left insula, postcentral gyrus and left precentral gyrus were shown in female OCD patients. Moreover, the fALFF values in left precentral gyrus and left middle temporal gyrus were positively associated with patients YBOCS-Obsessions scores and HAMD scores, respectively. Our findings bring additional insights in understanding the pathophysiology of female OCD patients.

Histamine elicits glutamate release from cultured astrocytes

Astrocytes play key roles in regulating brain homeostasis and neuronal activity. This is, in part, accomplished by the ability of neurotransmitters in the synaptic cleft to bind astrocyte membrane receptors, activating signalling cascades that regulate concentration of intracellular Ca2+ ([Ca2+]i) and gliotransmitter release, including ATP and glutamate. Gliotransmitters contribute to dendrite formation and synaptic plasticity, and in some cases, exacerbate neurodegeneration. The neurotransmitter histamine participates in several physiological processes, such as the sleep-wake cycle and learning and memory. Previous studies have demonstrated the expression of histamine receptors on astrocytes, but until now, only a few studies have examined the effects of histamine on astrocyte intracellular signalling and gliotransmitter release. Here, we used the human astrocytoma cell line 1321N1 to study the role of histamine in astrocyte intracellular signalling and gliotransmitter release. We found that histamine activated astrocyte signalling through histamine H1 and H2 receptors, leading to distinct cellular responses. Activation of histamine H1 receptors caused concentration-dependent release of [Ca2+]i from internal stores and concentration-dependent increase in glutamate release. Histamine H2 receptor activation increased cyclic adenosine monophosphate (cAMP) levels and phosphorylation of transcription factor cAMP response-element binding protein. Taken together, these data emphasize a role for histamine in neuron-glia communication.

The Effect of Applying Self- and Family-Oriented Written Education on the Management of Medicamentose, Clinical Exposure, and Quality of Life of Patient with Epilepsy

Epilepsy is a brain disorder characterized by a tendency to induce a continuous epileptic recurrence and neurobiological, cognitive, psychological, as well as social consequences. Epilepsy seizures are a series of signs and/or symptoms caused by abnormal neuronal activities in the brain. The purpose of this study was to prove the benefits of applying self- and family-oriented educational management to clinical outcomes, self-management, and impact of epilepsy on family, patient’s quality of life, family support, and the role of doctors and family of the epilepsy patient. This is an experimental research using two groups pre and posttest design. The subjects were 80 epilepsy patients ranging from 18 to 70 years of age. All subjects had never had any epilepsy surgery. The subjects were randomly assigned to treatment and control groups; 40 subjects in the treatment group received treatment and self- as well as family-oriented education while the other 40 subjects in the control group received treatment only. Family-oriented education was conducted using written materials on pathophysiology and epilepsy management, psychological effects of epilepsy, and information about the epilepsy community. All of the subjects answered the questionnaires prior to and 3 months after treatment. The questionnaires include information on seizure frequency and seizure-free status, medication adherence, self-management, epilepsy impact on patient and family, and quality of life. The results show that self- and family-oriented education can improve medication adherence, self-management, and family roles. Family-oriented education reduces the frequency of seizures as well as the impact of epilepsy on patients and families. It was concluded that self- and family-oriented education had a positive effect on medical management, clinical outcomes, self-management, and the quality of life of patients with epilepsy.

Resveratrol, a natural polyphenol, prevents chemotherapy-induced cognitive impairment: Involvement of cytokine modulation and neuroprotection

Chemotherapy-induced cognitive impairment, also known as “chemobrain,” is a common side effect. The purpose of this study was to examine whether resveratrol, a natural polyphenol that has nootropic effects, could prevent chemobrain and its underlying mechanisms. Mice received three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination, a common chemotherapy regimen, at two-day intervals within one week. Resveratrol (50 and 100 mg/kg per day) was orally administered for three weeks, beginning one week before the DAC treatment. Water maze test and manganese-enhanced magnetic resonance imaging were used to evaluate animals' cognitive performance and brain neuronal activity, respectively. Blood and brain tissues were collected for measurement of cytokines, cytokine regulators, and biomarkers for neuroplasticity. DAC treatment produced a striking cognitive impairment. Cotreatment with 100 mg/kg resveratrol ameliorated DAC-induced cognitive impairment and decreases in prefrontal and hippocampal neuronal activity. Mice co-treated with both doses of resveratrol displayed significantly lower levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but markedly higher levels of the anti-inflammatory cytokines IL-4 and IL-10 in several sera and brain tissues than those co-treated with vehicle. Resveratrol modulated the cytokine-regulating pathway peroxisome proliferator activated receptor (PPAR)-γ/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protected against DAC-induced decreases in the expression of the neuroplasticity biomarkers, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), amino acid neurotransmitter receptors, and calmodulin-dependent protein kinase II (CaMKII). These results demonstrate the efficacy of resveratrol in preventing chemobrain and its association with cytokine modulation and neuroprotection.

Monitoring brain neuronal activity with manipulation of cardiac events in a freely moving rat

Behavioral and cognitive studies have demonstrated that brain functions are affected by the activity states of the peripheral organs, such as the cardiac and respiratory systems. However, detailed neurophysiological mechanisms underlying the body-brain interactions remain unknown. In this study, we developed a method for manipulating activity levels of the heart using direct cardiac stimulation and vagus nerve stimulation that can be combined with recording cerebral local field potentials using a microdrive system, electrocardiograms, electromyograms, in a freely moving rat. With this method, the electrical stimulation to the heart increases heart rates up to 14 Hz, whereas the vagus nerve stimulation decreases heart rates to 3 Hz. Transient electrical artifacts arising from the peripheral stimulation are not contaminated in cortical local field potential signals low-pass filtered at 150 Hz and distinguishable from extracellular multiunit signals. The technique will contribute to understanding the neurophysiological correlate of mind-body associations in health and disease.

Head Immobilization in Experiments on Awake Animals: Minimization of Stress

An original head holder and a training procedure designed for better adaptation of animals to rigid immobilization carried out in experiments in the awake drug-free state without body and limb restraining are described. The head holder can be used autonomously or in combination with a standard stereotaxic apparatus; it provides possibilities for stable recording of brain neuronal activity and delivery of pharmacological drugs. The device may be successfully used in both electrophysiological and behavioral experiments, particularly in studies of sensory perception and eye-head coordination. The proposed head holder and flexible training program provide much weaker immobilization-induced stress-related effects, which preserves normal physiological functions of the animal. The device may be successfully used for different laboratory animal species.

Mass cytometry analysis of immune cells in the brain

Immune cells comprise a diverse and dynamic cell population that is responsible for a broad range of immunological activities. They act in concert with other immune and nonimmune cells via cytokine-mediated communication and direct cell-cell interactions. Understanding the complex immune network requires a broad characterization of its individual cellular components. This is especially relevant for the brain compartment, which is an active immunological site, composed of resident and infiltrating immune cells that affect brain development, tissue homeostasis and neuronal activity. Mass cytometry, or CyTOF (cytometry by time-of-flight), uses metal-conjugated antibodies to enable a high-dimensional description of tens of markers at the single-cell level, thereby providing a bird's-eye view of the immune system. This technique has been successfully applied to the discovery of novel immune populations in humans and rodents. Here, we provide a step-by-step description of a mass cytometry approach for the analysis of the mouse brain compartment. The different stages of the procedure include brain perfusion, extraction of the brain tissue and its dissociation into a single-cell suspension, followed by cell staining with metal-tagged antibodies, sample reading using a mass cytometer, and data analysis using SPADE and viSNE. This procedure takes <5 h (excluding data analysis) and can be applied to study modifications in the brain's immune populations under normal and pathological conditions.

The Influence of Surface Deformations on the Forward Magnetoencephalographic Problem

A perturbational model is developed providing explicit computationally efficient solutions for the forward magnetoencephalographic problem, namely, calculating the external magnetic fields for known neuronal sources. The aim of the study is to investigate the sensitivity of the particular measurements to deformations occurring on the conductor's surface. These geometric variations represent irregularities in head shapes and correspond to two major situations: (1) localized acquired injuries of the scalp-skull delivered by external forces; (2) craniofacial alterations due to natural mechanisms or defects. The presented methodology has the following advantages. First, it supports the installation of tailored functions, which individually describe aforesaid deformations. Second, it allows rapid calculation of the forward problem for superficial cerebral activity, where similar numerical methods produce large errors. Our results indicate that surface deformations can have an eminent impact on magnetoencephalographic measurements under the condition that the neuronal brain activity is located beneath the deformed area, as well as on the extent of the deformation itself. In situations where surface deformations are not taken into account, the error made, varying between 5 to 25 per cent, propagates with distance.

Facial expression awareness based on multi-scale permutation entropy of EEG

Electroencephalogram (EEG) is a comprehensive manifestation of the dynamic activity of human brain neurons and has been proven to have the potential to serve as an effective biomarker for identifying subtle emotion- or cognition-related changes. This paper focuses on facial expression awareness and proposes Multi-scale permutation Entropy (MPE) of EEG data with the aim of finding a convenient and accurate method for identifying different facial expressions. First, the principle and computational procedure of MPE is introduced. Then, MPE analysis of EEG for facial expression awareness is detailed. Finally, computational analysis is conducted. In the first experiment, the influence of the scale factor on the MPE values is investigated in which the entropy value tends to be augmented with an increase in the scale factor when the scale factor is less than five. In the second experiment, the analysis results show that the MPE of the angry expression EEG is higher than that of the happy expression EEG. Furthermore, we analysed the MPE in the form of a boxplot and found that the two expressions of anger and happiness can be distinguished clearly and that MPE can be used to predict angry and happy expressions based on EEG signals.

Advancements in EEG source localisation methods

Electroencephalogram (EEG) signals represent the neuronal activity of brain. These signals are recorded by placement of multiple electrodes over the scalp or from cortex of the brain under the skull. These signals have important applications in biomedical and clinical field but most applications fail to take benefit of all the data's available from the information, particularly about the location of dynamic sources in the brain. Localisation of sources of brain signal is important for the study of brain physiological, mental, pathological, and functional abnormalities, and problems related to various body disabilities. Their ultimate aim is to specify the sources of abnormalities such as tumours and epilepsy. This paper provides comprehensive overview of the different traditional and latest methods used for the EEG source localisation.

Advancements in EEG source localisation methods

Electroencephalogram (EEG) signals represent the neuronal activity of brain. These signals are recorded by placement of multiple electrodes over the scalp or from cortex of the brain under the skull. These signals have important applications in biomedical and clinical field but most applications fail to take benefit of all the data's available from the information, particularly about the location of dynamic sources in the brain. Localisation of sources of brain signal is important for the study of brain physiological, mental, pathological, and functional abnormalities, and problems related to various body disabilities. Their ultimate aim is to specify the sources of abnormalities such as tumours and epilepsy. This paper provides comprehensive overview of the different traditional and latest methods used for the EEG source localisation.

Evaluating the Effect of Repetitive Transcranial Magnetic Stimulation in Cerebral Palsy Children by Employing Electroencephalogram Signals.

Introduction:Transcranial magnetic stimulation is a new tool that has been employed to modulate the neuronal activity of brain by its excitatory and inhibitory property. In cerebral palsy (CP) learning of any new task is an extremely slow process due to damage in sensory and motor areas of brain affecting the cognitive ability of the child and putting constraints in achieving timely developmental milestones. For such patients the electroencephalogram (EEG) is one of the most cost effective diagnostic tools used that minimizes hospital stay. Its analysis helps to identify various neurological disorders determining the role of brain waves outlining the present status of mind.Materials and Methods:This study evaluated the EEG power spectrum density (PSD) of CP children both pre and post rTMS intervention to identify significance changes in signal patterns arising from different brain regions. thirty CP children participated in this study. Fifteen individuals underwent repetitive TMS (rTMS) therapy for 20 session comprising of 10 Hz frequency for 5 days a week for 4 weeks and another fifteen individual participated in activities of daily living for 20 sessions where they were administered mandatory standard therapy only. pre- EEG versus post EEG data recorded and analyzed employing the standard montage configuration. PSD was extracted employing fast fourier transform post acquisition of artifact free signal to undermine changes in signal pattern.Discussion and Conclusion:The results revealed that rTMS improves learning ability in CP children and it shows higher power peak at frequency of 50 Hz and lower power peak frequency at 100 Hz. The power intensity in gamma wave region shows significant reduction post-rTMS therapy between 38-24 power peak frequency and 7-4 range in 100 Hz power peak frequency. In future, it will be used as effective tool as memory enhancers, especially for children with neurological disorders.

BRAD: Software for BRain Activity Detection from hemodynamic response

Background and objective: Precise estimation of neuronal activity from neuroimaging data is one of the central challenges of the application of noninvasive neuroimaging methods. One of the widely used methods for studying brain activity is functional magnetic resonance imaging, which is a neuroimaging procedure that measures brain activity based on the blood oxygenation level dependent effect. The blood oxygenation level dependent signal can be modeled as a linear convolution of a hemodynamic response function with an input signal corresponding to the neuronal activity. Estimating such input signals is a complicated problem.Methods: We present a software tool for estimation of brain neuronal activity, which uses a combination of Wiener filtering with deconvolution methods, including the least absolute shrinkage and selection operator, the ordinary least squares method, and the Dantzig selector. The latter two are equipped with both established selection criteria (Akaike and Bayesian information criterion) as well as newly developed mixture criteria for selection of activations.Results: The software tool was tested on two types of data: measurements during basic visual experiments and during complex naturalistic audiovisual stimulation (watching a movie segment). During testing the software showed reasonable results, with the mixture criteria performing well for temporally extended activations.Conclusions: The presented software tool can be used for estimation, visualization, and analysis of brain neuronal activity from functional magnetic resonance imaging blood oxygenation level dependent measurements. The implemented methods provide valid results not only in the sparse activity scenario studied previously but also for temporally extended activations.