ROCKVILLE, MD, United States
ROCKVILLE, MD, United States

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Kim J.K.,Brain Bio | Fiorillo C.D.,Brain Bio
Nature Communications | Year: 2017

Synaptic inhibition counterbalances excitation, but it is not known what constitutes optimal inhibition. We previously proposed that perfect balance is achieved when the peak of an excitatory postsynaptic potential (EPSP) is exactly at spike threshold, so that the slightest variation in excitation determines whether a spike is generated. Using simulations, we show that the optimal inhibitory postsynaptic conductance (IPSG) increases in amplitude and decay rate as synaptic excitation increases from 1 to 800 Hz. As further proposed by theory, we show that optimal IPSG parameters can be learned through anti-Hebbian rules. Finally, we compare our theoretical optima to published experimental data from 21 types of neurons, in which rates of synaptic excitation and IPSG decay times vary by factors of about 100 (5-600 Hz) and 50 (1-50 ms), respectively. From an infinite range of possible decay times, theory predicted experimental decay times within less than a factor of 2. Across a distinct set of 15 types of neuron recorded in vivo, theory predicted the amplitude of synaptic inhibition within a factor of 1.7. Thus, the theory can explain biophysical quantities from first principles. © The Author(s) 2017.

Yuan Z.,University of Macau | Ye J.C.,Brain Bio
Frontiers in Human Neuroscience | Year: 2013

In this study we implemented a new imaging method to fuse functional near infrared spectroscopy (fNIRS) measurements and functional magnetic resonance imaging (fMRI) data to reveal the spatiotemporal dynamics of the hemodynamic responses with high spatiotemporal resolution across the brain. We evaluated this method using multimodal data acquired from human right finger tapping tasks. And we found the proposed method is able to clearly identify from the linked components of fMRI and fNIRS where and when the hemodynamic signals are changing. In particular, the estimated associations between fNIRS and fMRI will be displayed as time varying spatial fMRI maps along with the fNIRS time courses. In addition, the joint components between fMRI and fNIRS are combined together to generate full spatiotemporal "snapshots" and movies, which provides an excellent way to examine the dynamic interplay between hemodynamic fNIRS and fMRI measurements. © 2013 Yuan and Ye.

Choi J.K.,Brain Bio
IET Systems Biology | Year: 2010

Epigenetics is the study of regulatory mechanisms that are not accompanied by the action of genetic elements. Recently, a system-wide extension of epigenetics has been driven by the rapid evolution of genomics technology. This means not simply profiling multiple genes together as gene expression microarrays, but also factoring in the crosstalk among various epigenetic components and extending our focus to relatively uncharted genomic areas, including intergenic and intragenic regions. Although this exciting extension provides many interesting research topics as described in this review, the future expansion of epigenomics to cover multiple samples will offer an even more profound opportunity for systems biology research. © 2010 © The Institution of Engineering and Technology.

Whole-genome expression profiling in postmortem brain tissue has recently provided insight into the pathophysiology of schizophrenia. Previous microarray and RNA-Seq studies identified several biological processes including synaptic function, mitochondrial function and immune/inflammation response as altered in the cortex of subjects with schizophrenia. Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes in schizophrenia cases as compared with unaffected controls. Immune/inflammation response was the main biological process over-represented in these genes. The upregulation of several of these genes, IFITM1, IFITM2, IFITM3, APOL1 (Apolipoprotein L1), ADORA2A (adenosine receptor 2A), IGFBP4 and CD163 were validated in the schizophrenia subjects using data from the SNCID database and with quantitative RT-PCR. We identified a co-expression module associated with schizophrenia that includes the majority of differentially expressed genes related to immune/inflammation response as well as with the density of parvalbumin-containing neurons in the hippocampus. The results indicate that abnormal immune/inflammation response in the hippocampus may underlie the pathophysiology of schizophrenia and may be associated with abnormalities in the parvalbumin-containing neurons that lead to the cognitive deficits of the disease.

Jang M.J.,Brain Bio | Nam Y.,Brain Bio
Journal of Neural Engineering | Year: 2012

Recent advances in nano- and micro-technology have made it possible to deliver surface-bound extracellular signaling cues to cultured neurons. In this study, we investigated the formation of neurites and axonal outgrowth using various types of polygonal micropatterns ('micropolygon arrays') on cell culture substrates and suggested a novel design principle of in vitro axon guidance. Ten different types of micropolygons (circle, triangle, square, pentagon, hexagon, stars and isosceles triangles) were printed on a culture substrate using micro-contact printing with a mixture of poly-l-lysine and laminin A chain synthetic peptide. E18 rat hippocampal neurons were cultured on the patterned substrates, and the relation between micropatterns and neurite outgrowth was analyzed. Micropolygon arrays had effects on the soma shape and neurite initiation. In the case of regular triangle patterns, neurons showed vertex preference in terms of neurite initiation: neurites were more frequently generated from the vertex region. In the case of isosceles triangles, a major neurite was formed from the sharpest vertex and axons were developed from the sharpest vertex. Thus, the direction of axon growth could be controlled by the orientation of the sharpest vertex in the isosceles triangles. This work suggests that the geometry of cell adhesive regions influences the development of a cultured neuron, and the structure of neural circuits can be designed by controlling axonal outgrowth with individual micropolygons. © 2012 IOP Publishing Ltd.

Nam Y.,Brain Bio
MRS Bulletin | Year: 2012

As biological science advances, there is a need for new technical tools to study biological matters. In neuroscience, new knowledge on the nervous system is discovered through biological experiments carried out under in vitro conditions. As experiments become more delicate, the technical requirements also increase. Recent advances in nano-and microscale technologies have increased the applicability of new emerging technology to neurobiology and neural engineering. As a result, many materials that were not originally developed for neural interfaces have become attractive candidates to sense neural signals, stimulate neurons, and grow nerve cells for tissue engineering. This article focuses on the material requirements for in vitro neural interfaces and introduces materials that are used to design various neural interface platforms in vitro. © 2012 Materials Research Society.

Motivation: Complex physiological relationships exist among human diseases. Thus, the identification of disease associations could provide new methods of disease care and diagnosis. To this end, numerous studies have investigated disease associations. However, combinatorial effect of physiological factors, which is the main characteristic of biological systems, has not been considered in most previous studies.Results: In this study, we inferred disease associations with a novel approach that considered disease-related clinical factors in combinatorial ways by using the National Health and Nutrition Examination Survey data, and the results have been shown as disease networks. Here, the FP-growth algorithm, an association rule mining algorithm, was used to generate a clinical attribute combination profile of each disease. In addition, we characterized the 22 clinical risk attribute combinations frequently discovered from the 26 diseases in this study. Furthermore, we validated that the results of this study have great potential for drug repositioning and outperform other existing disease networks in this regard. Finally, we suggest a few disease pairs as new candidates for drug repositioning and provide the evidence of their associations from the literature.Contact: or information: Supplementary data are available at the Bioinformatics online. © 2013 The Author 2013. Published by Oxford University Press.

It has been proposed that the general function of the brain is inference, which corresponds quantitatively to the minimization of uncertainty (or the maximization of information). However, there has been a lack of clarity about exactly what this means. Efforts to quantify information have been in agreement that it depends on probabilities (through Shannon entropy), but there has long been a dispute about the definition of probabilities themselves. The "frequentist" view is that probabilities are (or can be) essentially equivalent to frequencies, and that they are therefore properties of a physical system, independent of any observer of the system. E.T. Jaynes developed the alternate "Bayesian" definition, in which probabilities are always conditional on a state of knowledge through the rules of logic, as expressed in the maximum entropy principle. In doing so, Jaynes and others provided the objective means for deriving probabilities, as well as a unified account of information and logic (knowledge and reason). However, neuroscience literature virtually never specifies any definition of probability, nor does it acknowledge any dispute concerning the definition. Although there has recently been tremendous interest in Bayesian approaches to the brain, even in the Bayesian literature it is common to find probabilities that are purported to come directly and unconditionally from frequencies. As a result, scientists have mistakenly attributed their own information to the neural systems they study. Here I argue that the adoption of a strictly Jaynesian approach will prevent such errors and will provide us with the philosophical and mathematical framework that is needed to understand the general function of the brain. Accordingly, our challenge becomes the identification of the biophysical basis of Jaynesian information and logic. I begin to address this issue by suggesting how we might identify a probability distribution over states of one physical system (an "object") conditional only on the biophysical state of another physical system (an "observer"). The primary purpose in doing so is not to characterize information and inference in exquisite, quantitative detail, but to be as clear and precise as possible about what it means to perform inference and how the biophysics of the brain could achieve this goal. © 2012 by the authors.

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.50M | Year: 2015

DESCRIPTION provided by applicant Advanced imaging technologies such as Positron Emission Tomography PET and Magnetic Resonance Imaging MR have led to remarkable improvement in our knowledge of brain metabolism function and biochemistry And yet our understanding of most neurological disorders is at best rudimentary Etiology of such common diseases as drug and alcohol addiction schizophrenia Alzheimerandapos s dementia and Parkinsonandapos s remains elusive Malignant brain tumors such as glioblastoma continue being fatal Changes happening in the brain in such common syndromes as hospital acquired delirium and post operative cognitive decline are not understood Most studies involving advanced brain imaging remain small due to logistical challenges cost constraints and difficulty of scanning neurological patients in standard radiology equipment Acceleration of brain research is required to elucidate the pathophysiology of neurological and psychiatric conditions Brain Biosciences was established to make neurological imaging comfortable inexpensive and widely available both in the clinic and in the research laboratory One of the common problems encountered in imaging research is unintentional patient motion Head movement during Positron Emission Tomography PET degrades PET image quality leads to image artifacts and introduces quantitative errors Motion is particularly common in confused patients with neurological diseases drug addiction and movement disorders This problem becomes especially relevant as research involving lengthy dynamic scans and high resolution brain imaging becomes common While sedation is often used to minimize the patient motion sedative drugs change brain biochemistry interfere with radiopharmaceutical uptake and may cause side effects Physical restraints are often distressing and may increase patient agitation In this direct Phase II SBIR proposal we seek to develop clinically validate and receive FDA clearance for FREEMotion tm a video based head tracking system enabling motion compensated brain Positron Emission Tomography PET imaging of neurological patients without sedation or physical head restraint PUBLIC HEALTH RELEVANCE This application proposes to develop and validate a novel head tracking system capable of compensating for patient motion during high resolution brain Positron Emission Tomography PET imaging This device will lower improve the quality comfort and quantification of brain PET in patients with neurological and psychiatric diseases as well as drug abuse The proposed device will have applications both in the clinic and neuroscience research

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.59M | Year: 2015

DESCRIPTION provided by applicant Neurodegenerative diseases such as Alzheimer and other dementias present significant societal and economic burden The number of patients suffering from these disorders grows rapidly owing to the aging of the world population Alzheimerandapos s Association projects that the number of Americans living with Alzheimerandapos s disease AD will increase from M today to M in Management and treatment of brain disorders is a critical task facing the healthcare innovation system continuing progress in this field will depend on early high confidence diagnosis Amyloid imaging agents the new promising class of Positron Emission Tomography PET radiopharmaceuticals enable diagnosis of Alzheimerandapos s pathology at the early stages of disease Brain Biosciences seeks to make neurological PET imaging affordable and widely available both in the clinic and in the research laboratory To achieve this goal we aim to develop validate and obtain k FDA clearance for CerePETandquot a compact portable high performance and cost effective PET scanner for brain imaging This innovative device is designed to achieve high resolution at a fraction of the cost of currently marketed whole body PET systems CerePET applications include i evaluation of amyloid burden in patients with suspected Alzheimer disease mild cognitive impairment and other neurodegenerative disorders ii multicenter clinical trials of CNS targeted pharmaceuticals using PET scan as a biomarker iii clinical neuroscience research During this Fast track SBIR project CerePET will be rigorously validated using a set of internationally recognized tests CerePET imaging performance will be characterized per NEMA NU the scanner will be used in a clinical study comparing amyloid burden in patients with Alzheimerandapos s disease and healthy controls PUBLIC HEALTH RELEVANCE This application proposes to develop small footprint high performance Positron Emission Tomography PET scanner optimized for brain imaging This device will lower the cost and increase availability of neurological PET examinations both in the clinical and research settings

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