Neurodevelopmental effects of chronic exposure to elevated levels of pro-inflammatory cytokines in a developing visual system

PubMed Central

2010-01-01

Background Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with a number of severe and prevalent neurodevelopmental disorders, including autism spectrum disorder, schizophrenia and Down syndrome. Although several studies have shown that cytokines have potent effects on neural function, their role in neural development is still poorly understood. In this study, we investigated the link between abnormal cytokine levels and neural development using the Xenopus laevis tadpole visual system, a model frequently used to examine the anatomical and functional development of neural circuits. Results Using a test for a visually guided behavior that requires normal visual system development, we examined the long-term effects of prolonged developmental exposure to three pro-inflammatory cytokines with known neural functions: interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. We found that all cytokines affected the development of normal visually guided behavior. Neuroanatomical imaging of the visual projection showed that none of the cytokines caused any gross abnormalities in the anatomical organization of this projection, suggesting that they may be acting at the level of neuronal microcircuits. We further tested the effects of TNF-α on the electrophysiological properties of the retinotectal circuit and found that long-term developmental exposure to TNF-α resulted in enhanced spontaneous excitatory synaptic transmission in tectal neurons, increased AMPA/NMDA ratios of retinotectal synapses, and a decrease in the number of immature synapses containing only NMDA receptors, consistent with premature maturation and stabilization of these synapses. Local interconnectivity within the tectum also appeared to remain widespread, as shown by increased recurrent polysynaptic activity, and was similar to what is seen in more immature, less refined tectal circuits. TNF-α treatment also enhanced the overall growth of tectal cell dendrites. Finally, we found that TNF-α-reared tadpoles had increased susceptibility to pentylenetetrazol-induced seizures. Conclusions Taken together our data are consistent with a model in which TNF-α causes premature stabilization of developing synapses within the tectum, therefore preventing normal refinement and synapse elimination that occurs during development, leading to increased local connectivity and epilepsy. This experimental model also provides an integrative approach to understanding the effects of cytokines on the development of neural circuits and may provide novel insights into the etiology underlying some neurodevelopmental disorders. PMID:20067608

Neurodevelopmental effects of chronic exposure to elevated levels of pro-inflammatory cytokines in a developing visual system.

PubMed

Lee, Ryan H; Mills, Elizabeth A; Schwartz, Neil; Bell, Mark R; Deeg, Katherine E; Ruthazer, Edward S; Marsh-Armstrong, Nicholas; Aizenman, Carlos D

2010-01-12

Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with a number of severe and prevalent neurodevelopmental disorders, including autism spectrum disorder, schizophrenia and Down syndrome. Although several studies have shown that cytokines have potent effects on neural function, their role in neural development is still poorly understood. In this study, we investigated the link between abnormal cytokine levels and neural development using the Xenopus laevis tadpole visual system, a model frequently used to examine the anatomical and functional development of neural circuits. Using a test for a visually guided behavior that requires normal visual system development, we examined the long-term effects of prolonged developmental exposure to three pro-inflammatory cytokines with known neural functions: interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha. We found that all cytokines affected the development of normal visually guided behavior. Neuroanatomical imaging of the visual projection showed that none of the cytokines caused any gross abnormalities in the anatomical organization of this projection, suggesting that they may be acting at the level of neuronal microcircuits. We further tested the effects of TNF-alpha on the electrophysiological properties of the retinotectal circuit and found that long-term developmental exposure to TNF-alpha resulted in enhanced spontaneous excitatory synaptic transmission in tectal neurons, increased AMPA/NMDA ratios of retinotectal synapses, and a decrease in the number of immature synapses containing only NMDA receptors, consistent with premature maturation and stabilization of these synapses. Local interconnectivity within the tectum also appeared to remain widespread, as shown by increased recurrent polysynaptic activity, and was similar to what is seen in more immature, less refined tectal circuits. TNF-alpha treatment also enhanced the overall growth of tectal cell dendrites. Finally, we found that TNF-alpha-reared tadpoles had increased susceptibility to pentylenetetrazol-induced seizures. Taken together our data are consistent with a model in which TNF-alpha causes premature stabilization of developing synapses within the tectum, therefore preventing normal refinement and synapse elimination that occurs during development, leading to increased local connectivity and epilepsy. This experimental model also provides an integrative approach to understanding the effects of cytokines on the development of neural circuits and may provide novel insights into the etiology underlying some neurodevelopmental disorders.

Neural correlates of deception in social contexts in normally developing children

PubMed Central

Yokota, Susumu; Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Thyreau, Benjamin; Tanaka, Mari; Kawashima, Ryuta

2013-01-01

Deception is related to the ability to inhibit prepotent responses and to engage in mental tasks such as anticipating responses and inferring what another person knows, especially in social contexts. However, the neural correlates of deception processing, which requires mentalizing, remain unclear. Using functional magnetic resonance imaging (fMRI), we examined the neural correlates of deception, including mentalization, in social contexts in normally developing children. Healthy right-handed children (aged 8–9 years) were scanned while performing interactive games involving deception. The games varied along two dimensions: the type of reply (deception and truth) and the type of context (social and less social). Participants were instructed to deceive a witch and to tell the truth to a girl. Under the social-context conditions, participants were asked to consider what they inferred about protagonists' preferences from their facial expressions when responding to questions. Under the less-social-context conditions, participants did not need to consider others' preferences. We found a significantly greater response in the right precuneus under the social-context than under less-social-context conditions. Additionally, we found marginally greater activation in the right inferior parietal lobule (IPL) under the deception than under the truth condition. These results suggest that deception in a social context requires not only inhibition of prepotent responses but also engagement in mentalizing processes. This study provides the first evidence of the neural correlates of the mentalizing processes involved in deception in normally developing children. PMID:23730281

Comparative analysis of neural network and regression based condition monitoring approaches for wind turbine fault detection

NASA Astrophysics Data System (ADS)

Schlechtingen, Meik; Ferreira Santos, Ilmar

2011-07-01

This paper presents the research results of a comparison of three different model based approaches for wind turbine fault detection in online SCADA data, by applying developed models to five real measured faults and anomalies. The regression based model as the simplest approach to build a normal behavior model is compared to two artificial neural network based approaches, which are a full signal reconstruction and an autoregressive normal behavior model. Based on a real time series containing two generator bearing damages the capabilities of identifying the incipient fault prior to the actual failure are investigated. The period after the first bearing damage is used to develop the three normal behavior models. The developed or trained models are used to investigate how the second damage manifests in the prediction error. Furthermore the full signal reconstruction and the autoregressive approach are applied to further real time series containing gearbox bearing damages and stator temperature anomalies. The comparison revealed all three models being capable of detecting incipient faults. However, they differ in the effort required for model development and the remaining operational time after first indication of damage. The general nonlinear neural network approaches outperform the regression model. The remaining seasonality in the regression model prediction error makes it difficult to detect abnormality and leads to increased alarm levels and thus a shorter remaining operational period. For the bearing damages and the stator anomalies under investigation the full signal reconstruction neural network gave the best fault visibility and thus led to the highest confidence level.

Development of an automatic rotational orthosis for walking with arm swing.

PubMed

Fang, Juan; Yang, Guo-Yuan; Xie, Le

2017-07-01

Interlimb neural coupling is often observed during normal gait and is postulated to be important for gait restoration. In order to provide a testbed for investigation of interlimb neural coupling, we previously developed a rotational orthosis for walking with arm swing (ROWAS). The present study aimed to develop and evaluate the feasibility of a new system, viz. an automatic ROWAS (aROWAS). We developed the mechanical structures of aROWAS in SolidWorks, and implemented the concept in a prototype. Normal gait data from walking at various speeds were used as reference trajectories of the shoulder, hip, knee and ankle joints. The aROWAS prototype was tested in three able-bodied subjects. The prototype could automatically adjust to size and height, and automatically produced adaptable coordinated performance in the upper and lower limbs, with joint profiles similar to those occurring in normal gait. The subjects reported better acceptance in aROWAS than in ROWAS. The aROWAS system was deemed feasible among able-bodied subjects.

The eye limits the brain's learning potential

PubMed Central

Zhou, Jiawei; Zhang, Yudong; Dai, Yun; Zhao, Haoxin; Liu, Rong; Hou, Fang; Liang, Bo; Hess, Robert F.; Zhou, Yifeng

2012-01-01

The concept of a critical period for visual development early in life during which sensory experience is essential to normal neural development is now well established. However recent evidence suggests that a limited degree of plasticity remains after this period and well into adulthood. Here, we ask the question, "what limits the degree of plasticity in adulthood?" Although this limit has been assumed to be due to neural factors, we show that the optical quality of the retinal image ultimately limits the brain potential for change. We correct the high-order aberrations (HOAs) normally present in the eye's optics using adaptive optics, and reveal a greater degree of neuronal plasticity than previously appreciated. PMID:22509464

Meninges harbor cells expressing neural precursor markers during development and adulthood.

PubMed

Bifari, Francesco; Berton, Valeria; Pino, Annachiara; Kusalo, Marijana; Malpeli, Giorgio; Di Chio, Marzia; Bersan, Emanuela; Amato, Eliana; Scarpa, Aldo; Krampera, Mauro; Fumagalli, Guido; Decimo, Ilaria

2015-01-01

Brain and skull developments are tightly synchronized, allowing the cranial bones to dynamically adapt to the brain shape. At the brain-skull interface, meninges produce the trophic signals necessary for normal corticogenesis and bone development. Meninges harbor different cell populations, including cells forming the endosteum of the cranial vault. Recently, we and other groups have described the presence in meninges of a cell population endowed with neural differentiation potential in vitro and, after transplantation, in vivo. However, whether meninges may be a niche for neural progenitor cells during embryonic development and in adulthood remains to be determined. In this work we provide the first description of the distribution of neural precursor markers in rat meninges during development up to adulthood. We conclude that meninges share common properties with the classical neural stem cell niche, as they: (i) are a highly proliferating tissue; (ii) host cells expressing neural precursor markers such as nestin, vimentin, Sox2 and doublecortin; and (iii) are enriched in extracellular matrix components (e.g., fractones) known to bind and concentrate growth factors. This study underlines the importance of meninges as a potential niche for endogenous precursor cells during development and in adulthood.

Meninges harbor cells expressing neural precursor markers during development and adulthood

PubMed Central

Bifari, Francesco; Berton, Valeria; Pino, Annachiara; Kusalo, Marijana; Malpeli, Giorgio; Di Chio, Marzia; Bersan, Emanuela; Amato, Eliana; Scarpa, Aldo; Krampera, Mauro; Fumagalli, Guido; Decimo, Ilaria

2015-01-01

Brain and skull developments are tightly synchronized, allowing the cranial bones to dynamically adapt to the brain shape. At the brain-skull interface, meninges produce the trophic signals necessary for normal corticogenesis and bone development. Meninges harbor different cell populations, including cells forming the endosteum of the cranial vault. Recently, we and other groups have described the presence in meninges of a cell population endowed with neural differentiation potential in vitro and, after transplantation, in vivo. However, whether meninges may be a niche for neural progenitor cells during embryonic development and in adulthood remains to be determined. In this work we provide the first description of the distribution of neural precursor markers in rat meninges during development up to adulthood. We conclude that meninges share common properties with the classical neural stem cell niche, as they: (i) are a highly proliferating tissue; (ii) host cells expressing neural precursor markers such as nestin, vimentin, Sox2 and doublecortin; and (iii) are enriched in extracellular matrix components (e.g., fractones) known to bind and concentrate growth factors. This study underlines the importance of meninges as a potential niche for endogenous precursor cells during development and in adulthood. PMID:26483637

Evidence that the notochord may be pivotal in the development of sacral and anorectal malformations.

PubMed

Qi, Bao Quan; Beasley, Spencer W; Frizelle, Francis A

2003-09-01

The notochord is known to organize normal development of central axial structures, such as the spinal cord, vertebral column, and anorectum, but its role in abnormal development of these organs has not been well documented. The current study has used Ethylenethiourea to induce anorectal malformations in fetal rats, allowing investigation of abnormalities of the notochord and their relationship to the axial structural abnormalities that occur. Timed-mated pregnant rats were fed Ethylenethiourea by gavage on gestational day 10. Their embryos were harvested on gestational days 13 to 16 and sectioned in either the transverse or sagittal plane. Sections were stained with H and E and examined serially. Anorectal malformations were identified in 29 of 34 embryos and neural tube defects in 24, ranging from an accessory neural tube to lumbo-sacral rachischisis. There was no tail or only a rudimentary tail in the majority of embryos. Abnormalities of the notochord in the lumbo-sacral area included ventro-dorsal branching, ventral deviation, and ectopic notochordal tissue. Most abnormal notochord branches and ectopic notochordal tissue were abnormally close to or in contact with the wall of the cloaca or neural tube. Given the known role of the notochord in controlling normal development, this study would suggest that abnormal notochord development may be pivotal in producing neural tube defects and anorectal malformations, possibly by altering sonic hedgehog signalling.

Development of the posterior neural tube in human embryos.

PubMed

Saitsu, Hirotomo; Yamada, Shigehito; Uwabe, Chigako; Ishibashi, Makoto; Shiota, Kohei

2004-12-01

Development of the posterior neural tube (PNT) in human embryos is a complicated process that involves both primary and secondary neurulation. Because normal development of the PNT is not fully understood, pathogenesis of spinal neural tube defects remains elusive. To clarify the mechanism of PNT development, we histologically examined 20 human embryos around the stage of posterior neuropore closure and found that the developing PNT can be divided into three parts: 1) the most rostral region, which corresponds to the posterior part of the primary neural tube, 2) the junctional region of the primary and secondary neural tubes, and 3) the caudal region, which emerges from the neural cord. In the junctional region, the axially-condensed mesenchyme (AM) intervened between the neural plate/tube and the notochord at the stage of posterior neuropore closure, while the notochord was directly attached to the neural plate/tube in the most rostral region. A single cavity was found to be formed in the AM as the presumptive luminal surface cells were radially aligned in the junctional region prior to the formation of the neural cord. The single cavity was continuous with the central cavity of the primary neural tube. In contrast, multiple or isolated cavities were frequently observed in the caudal region of the PNT. Our observation suggests that the junctional region of the PNT is distinct from other regions in terms of the relationship with the notochord and the mode of cavitation during secondary neurulation.

Gap-Junctional communication between developing Drosophila muscles is essential for their normal development.

PubMed

Todman, M G; Baines, R A; Stebbings, L A; Davies, J A; Bacon, J P

1999-01-01

Recent experiments have demonstrated that a family of proteins, known as the innexins, are structural components of invertebrate gap junctions. The shaking-B (shak-B) locus of Drosophila encodes two members of this emerging family, Shak-B(lethal) and Shak-B(neural). This study focuses on the role of Shak-B gap junctions in the development of embryonic and larval muscle. During embryogenesis, shak-B transcripts are expressed in a subset of the somatic muscles; expression is strong in ventral oblique muscles (VO4-6) but only weak in ventral longitudinals (VL3 and 4). Carboxyfluorescein injected into VO4 of wild-type early stage 16 embryos spreads, via gap junctions, to label adjacent muscles, including VL3 and 4. In shak-B2 embryos (in which the shak-B(neural) function is disrupted), dye injected into VO4 fails to spread into other muscles. In the first instar larva, when dye coupling between muscles is no longer present, another effect of the shak-B2 mutation is revealed by whole-cell voltage clamp. In a calcium-free saline, only two voltage-activated potassium currents are present in wild-type muscles; a fast IA and a slow IK current. In shak-B2 larvae, these two currents are significantly reduced in magnitude in VO4 and 5, but remain normal in VL3. Expression of shak-B(neural) in a shak-B2 background fully rescues both dye coupling in embryonic muscle and whole-cell currents in first instar VO4 and 5. Our observations show that Shak-B(neural) is one of a set of embryonic gap-junction proteins, and that it is required for the normal temporal development of potassium currents in some larval muscles.

Axial mesendoderm refines rostrocaudal pattern in the chick nervous system.

PubMed

Rowan, A M; Stern, C D; Storey, K G

1999-07-01

There has long been controversy concerning the role of the axial mesoderm in the induction and rostrocaudal patterning of the vertebrate nervous system. Here we investigate the neural inducing and regionalising properties of defined rostrocaudal regions of head process/prospective notochord in the chick embryo by juxtaposing these tissues with extraembryonic epiblast or neural plate explants. We localise neural inducing signals to the emerging head process and using a large panel of region-specific neural markers, show that different rostrocaudal levels of the head process derived from headfold stage embryos can induce discrete regions of the central nervous system. However, we also find that rostral and caudal head process do not induce expression of any of these molecular markers in explants of the neural plate. During normal development the head process emerges beneath previously induced neural plate, which we show has already acquired some rostrocaudal character. Our findings therefore indicate that discrete regions of axial mesendoderm at headfold stages are not normally responsible for the establishment of rostrocaudal pattern in the neural plate. Strikingly however, we do find that caudal head process inhibits expression of rostral genes in neural plate explants. These findings indicate that despite the ability to induce specific rostrocaudal regions of the CNS de novo, signals provided by the discrete regions of axial mesendoderm do not appear to establish regional differences, but rather refine the rostrocaudal character of overlying neuroepithelium.

Analysis and classification of normal and pathological skin tissue spectra using neural networks

NASA Astrophysics Data System (ADS)

Bruch, Reinhard F.; Afanasyeva, Natalia I.; Gummuluri, Satyashree

2000-07-01

An innovative spectroscopic diagnostic method has been developed for investigation of different regions of normal human skin tissue, as well as cancerous and precancerous conditions in vivo, ex vivo and in vitro. This new method is a combination of fiber-optical evanescent wave Fourier Transform infrared (FEW-FTIR) spectroscopy and fiber optic techniques using low-loss, highly flexible and nontoxic fiber optical sensors. The FEW-FTIR technique is nondestructive and very sensitive to changes of vibrational spectra in the IR region without heating and staining and thus altering the skin tissue. A special software package was developed for the treatment of the spectra. This package includes a database, programs for data preparation and presentation, and neural networks for classification of disease states. An unsupervised neural competitive learning neural network is implemented for skin cancer diagnosis. In this study, we have investigated and classified skin tissue in the range of 1400 to 1800 cm-1 using these programs. The results of our surface analysis of skin tissue are discussed in terms of molecular structural similarities and differences as well as in terms of different skin states represented by eleven different skin spectra classes.

Specific aspects of cognitive and language proficiency account for variability in neural indices of semantic and syntactic processing in children.

PubMed

Hampton Wray, Amanda; Weber-Fox, Christine

2013-07-01

The neural activity mediating language processing in young children is characterized by large individual variability that is likely related in part to individual strengths and weakness across various cognitive abilities. The current study addresses the following question: How does proficiency in specific cognitive and language functions impact neural indices mediating language processing in children? Thirty typically developing seven- and eight-year-olds were divided into high-normal and low-normal proficiency groups based on performance on nonverbal IQ, auditory word recall, and grammatical morphology tests. Event-related brain potentials (ERPs) were elicited by semantic anomalies and phrase structure violations in naturally spoken sentences. The proficiency for each of the specific cognitive and language tasks uniquely contributed to specific aspects (e.g., timing and/or resource allocation) of neural indices underlying semantic (N400) and syntactic (P600) processing. These results suggest that distinct aptitudes within broader domains of cognition and language, even within the normal range, influence the neural signatures of semantic and syntactic processing. Furthermore, the current findings have important implications for the design and interpretation of developmental studies of ERPs indexing language processing, and they highlight the need to take into account cognitive abilities both within and outside the classic language domain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neural substrates related to auditory working memory comparisons in dyslexia: An fMRI study

PubMed Central

CONWAY, TIM; HEILMAN, KENNETH M.; GOPINATH, KAUNDINYA; PECK, KYUNG; BAUER, RUSSELL; BRIGGS, RICHARD W.; TORGESEN, JOSEPH K.; CROSSON, BRUCE

2010-01-01

Adult readers with developmental phonological dyslexia exhibit significant difficulty comparing pseudowords and pure tones in auditory working memory (AWM). This suggests deficient AWM skills for adults diagnosed with dyslexia. Despite behavioral differences, it is unknown whether neural substrates of AWM differ between adults diagnosed with dyslexia and normal readers. Prior neuroimaging of adults diagnosed with dyslexia and normal readers, and post-mortem findings of neural structural anomalies in adults diagnosed with dyslexia support the hypothesis of atypical neural activity in temporoparietal and inferior frontal regions during AWM tasks in adults diagnosed with dyslexia. We used fMRI during two binaural AWM tasks (pseudowords or pure tones comparisons) in adults diagnosed with dyslexia (n = 11) and normal readers (n = 11). For both AWM tasks, adults diagnosed with dyslexia exhibited greater activity in left posterior superior temporal (BA 22) and inferior parietal regions (BA 40) than normal readers. Comparing neural activity between groups and between stimuli contrasts (pseudowords vs. tones), adults diagnosed with dyslexia showed greater primary auditory cortex activity (BA 42; tones > pseudowords) than normal readers. Thus, greater activity in primary auditory, posterior superior temporal, and inferior parietal cortices during linguistic and non-linguistic AWM tasks for adults diagnosed with dyslexia compared to normal readers indicate differences in neural substrates of AWM comparison tasks. PMID:18577292

A TMS Study of the Ventral Projections from V1 with Implications for the Finding of Neural Correlates of Consciousness

ERIC Educational Resources Information Center

Overgaard, Morten; Nielsen, Jorgen Feldbaek; Fuglsang-Frederiksen, Anders

2004-01-01

The study of subliminal perception in normal and brain lesioned subjects has long been of interest to scholars studying the neural mechanisms behind conscious vision. Using brief durations and a developed methodology of introspective reporting, we present an experiment with visual stimuli that gives rise to little or no subliminal perception under…

Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

PubMed Central

2017-01-01

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer's disease-related protein aggregation as an underlying mechanism of age-related memory impairment. SIGNIFICANCE STATEMENT Alterations in episodic memory and the accumulation of Alzheimer's pathology are common in cognitively normal older adults. However, evidence of pathological effects on episodic memory has largely been limited to β-amyloid (Aβ). Because Aβ and tau often cooccur in older adults, previous research offers an incomplete understanding of the relationship between pathology and episodic memory. With the recent development of in vivo tau PET radiotracers, we show that Aβ and tau are associated with different aspects of memory encoding, leading to aberrant neural activity that is behaviorally detrimental. In addition, our results provide evidence linking Aβ- and tau-associated neural dysfunction to brain atrophy. PMID:28213439

Aberrant differentiation of the axially condensed tail bud mesenchyme in human embryos with lumbosacral myeloschisis.

PubMed

Saitsu, Hirotomo; Yamada, Shigehito; Uwabe, Chigako; Ishibashi, Makoto; Shiota, Kohei

2007-03-01

Development of the posterior neural tube (PNT) in human embryos is a complicated process that involves both primary and secondary neurulation. Recently, we histologically examined 20 human embryos around the stage of posterior neuropore closure and found that the axially condensed mesenchyme (AM) intervened between the neural plate/tube and the notochord in the junctional region of the primary and secondary neural tubes. The AM appeared to be incorporated into the most ventral part of the primary neural tube, and no cavity was observed in the AM. In this study, we report three cases of human embryos with myeloschisis in which the open primary neural tube and the closed secondary neural tube overlap dorsoventrally. In all three cases, part of the closed neural tube was located ventrally to the open neural tube in the lumbosacral region. The open and closed neural tubes appeared to be part of the primary and the AM-derived secondary neural tubes, respectively. Thus, these findings suggest that, in those embryos with myeloschisis, the AM may not be incorporated into the ventral part of the primary neural tube but aberrantly differentiate into the secondary neural tube containing cavities, leading to dorsoventral overlapping of the primary and secondary neural tubes. The aberrant differentiation of the AM in embryos with lumbosacral myeloschisis suggests that the AM plays some roles in normal as well as abnormal development of the human posterior neural tube.

Normalization is a general neural mechanism for context-dependent decision making

PubMed Central

Louie, Kenway; Khaw, Mel W.; Glimcher, Paul W.

2013-01-01

Understanding the neural code is critical to linking brain and behavior. In sensory systems, divisive normalization seems to be a canonical neural computation, observed in areas ranging from retina to cortex and mediating processes including contrast adaptation, surround suppression, visual attention, and multisensory integration. Recent electrophysiological studies have extended these insights beyond the sensory domain, demonstrating an analogous algorithm for the value signals that guide decision making, but the effects of normalization on choice behavior are unknown. Here, we show that choice models using normalization generate significant (and classically irrational) choice phenomena driven by either the value or number of alternative options. In value-guided choice experiments, both monkey and human choosers show novel context-dependent behavior consistent with normalization. These findings suggest that the neural mechanism of value coding critically influences stochastic choice behavior and provide a generalizable quantitative framework for examining context effects in decision making. PMID:23530203

Neurostimulation and neuromodulation: a guide to selecting the right urologic patient.

PubMed

Schmidt, R A; Doggweiler, R

1998-01-01

Sensory input has an important influence on the integrity of neural circuitry. Central nervous system circuitry is programmed and reinforced by everyday experience. Even the simplest of behaviors participate in this process. A balance between inhibition and facilitation must be maintained for the CNS to function normally. For example, the bladder stores urine because of the inhibition from a closed sphincter, and relaxation of the sphincter disinhibits the bladder to permit voiding. This synergistic 'seesaw' in reflex neural activity preserves the functional and anatomical integrity of the lower urinary tract. Dysfunction and anatomical change results when an unnatural bias develops between inhibitory and facilitatory neural activity. Neurostimulation has an inherent conditioning effect on neural excitability and can restore the neural equilibrium. Voiding diaries are very useful in documenting these changes.

When modularization fails to occur: a developmental perspective.

PubMed

D'Souza, Dean; Karmiloff-Smith, Annette

2011-05-01

We argue that models of adult cognition defined in terms of independently functioning modules cannot be applied to development, whether typical or atypical. The infant brain starts out highly interconnected, and it is only over developmental time that neural networks become increasingly specialized-that is, relatively modularized. In the case of atypical development, even when behavioural scores fall within the normal range, they are frequently underpinned by different cognitive and neural processes. In other words, in neurodevelopmental disorders the gradual process of relative modularization may fail to occur.

Increasing Spontaneous Retinal Activity before Eye Opening Accelerates the Development of Geniculate Receptive Fields

PubMed Central

Davis, Zachary W.; Chapman, Barbara

2015-01-01

Visually evoked activity is necessary for the normal development of the visual system. However, little is known about the capacity for patterned spontaneous activity to drive the maturation of receptive fields before visual experience. Retinal waves provide instructive retinotopic information for the anatomical organization of the visual thalamus. To determine whether retinal waves also drive the maturation of functional responses, we increased the frequency of retinal waves pharmacologically in the ferret (Mustela putorius furo) during a period of retinogeniculate development before eye opening. The development of geniculate receptive fields after receiving these increased neural activities was measured using single-unit electrophysiology. We found that increased retinal waves accelerate the developmental reduction of geniculate receptive field sizes. This reduction is due to a decrease in receptive field center size rather than an increase in inhibitory surround strength. This work reveals an instructive role for patterned spontaneous activity in guiding the functional development of neural circuits. SIGNIFICANCE STATEMENT Patterned spontaneous neural activity that occurs during development is known to be necessary for the proper formation of neural circuits. However, it is unknown whether the spontaneous activity alone is sufficient to drive the maturation of the functional properties of neurons. Our work demonstrates for the first time an acceleration in the maturation of neural function as a consequence of driving patterned spontaneous activity during development. This work has implications for our understanding of how neural circuits can be modified actively to improve function prematurely or to recover from injury with guided interventions of patterned neural activity. PMID:26511250

Annotation: Development of Facial Expression Recognition from Childhood to Adolescence--Behavioural and Neurological Perspectives

ERIC Educational Resources Information Center

Herba, Catherine; Phillips, Mary

2004-01-01

Background: Intact emotion processing is critical for normal emotional development. Recent advances in neuroimaging have facilitated the examination of brain development, and have allowed for the exploration of the relationships between the development of emotion processing abilities, and that of associated neural systems. Methods: A literature…

Hypoxia promotes production of neural crest cells in the embryonic head.

PubMed

Scully, Deirdre; Keane, Eleanor; Batt, Emily; Karunakaran, Priyadarssini; Higgins, Debra F; Itasaki, Nobue

2016-05-15

Hypoxia is encountered in either pathological or physiological conditions, the latter of which is seen in amniote embryos prior to the commencement of a functional blood circulation. During the hypoxic stage, a large number of neural crest cells arise from the head neural tube by epithelial-to-mesenchymal transition (EMT). As EMT-like cancer dissemination can be promoted by hypoxia, we investigated whether hypoxia contributes to embryonic EMT. Using chick embryos, we show that the hypoxic cellular response, mediated by hypoxia-inducible factor (HIF)-1α, is required to produce a sufficient number of neural crest cells. Among the genes that are involved in neural crest cell development, some genes are more sensitive to hypoxia than others, demonstrating that the effect of hypoxia is gene specific. Once blood circulation becomes fully functional, the embryonic head no longer produces neural crest cells in vivo, despite the capability to do so in a hypoxia-mimicking condition in vitro, suggesting that the oxygen supply helps to stop emigration of neural crest cells in the head. These results highlight the importance of hypoxia in normal embryonic development. © 2016. Published by The Company of Biologists Ltd.

Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve.

PubMed

Odelin, Gaëlle; Faure, Emilie; Coulpier, Fanny; Di Bonito, Maria; Bajolle, Fanny; Studer, Michèle; Avierinos, Jean-François; Charnay, Patrick; Topilko, Piotr; Zaffran, Stéphane

2018-01-03

Although cardiac neural crest cells are required at early stages of arterial valve development, their contribution during valvular leaflet maturation remains poorly understood. Here, we show in mouse that neural crest cells from pre-otic and post-otic regions make distinct contributions to the arterial valve leaflets. Genetic fate-mapping analysis of Krox20-expressing neural crest cells shows a large contribution to the borders and the interleaflet triangles of the arterial valves. Loss of Krox20 function results in hyperplastic aortic valve and partially penetrant bicuspid aortic valve formation. Similar defects are observed in neural crest Krox20 -deficient embryos. Genetic lineage tracing in Krox20 -/- mutant mice shows that endothelial-derived cells are normal, whereas neural crest-derived cells are abnormally increased in number and misplaced in the valve leaflets. In contrast, genetic ablation of Krox20 -expressing cells is not sufficient to cause an aortic valve defect, suggesting that adjacent cells can compensate this depletion. Our findings demonstrate a crucial role for Krox20 in arterial valve development and reveal that an excess of neural crest cells may be associated with bicuspid aortic valve. © 2018. Published by The Company of Biologists Ltd.

Genetically induced abnormal cranial development in human trisomy 18 with holoprosencephaly: comparisons with the normal tempo of osteogenic-neural development.

PubMed

Reid, Shaina N; Ziermann, Janine M; Gondré-Lewis, Marjorie C

2015-07-01

Craniofacial malformations are common congenital defects caused by failed midline inductive signals. These midline defects are associated with exposure of the fetus to exogenous teratogens and with inborn genetic errors such as those found in Down, Patau, Edwards' and Smith-Lemli-Opitz syndromes. Yet, there are no studies that analyze contributions of synchronous neurocranial and neural development in these disorders. Here we present the first in-depth analysis of malformations of the basicranium of a holoprosencephalic (HPE) trisomy 18 (T18; Edwards' syndrome) fetus with synophthalmic cyclopia and alobar HPE. With a combination of traditional gross dissection and state-of-the-art computed tomography, we demonstrate the deleterious effects of T18 caused by a translocation at 18p11.31. Bony features included a single developmentally unseparated frontal bone, and complete dual absence of the anterior cranial fossa and ethmoid bone. From a superior view with the calvarium plates removed, there was direct visual access to the orbital foramen and hard palate. Both the eyes and the pituitary gland, normally protected by bony structures, were exposed in the cranial cavity and in direct contact with the brain. The middle cranial fossa was shifted anteriorly, and foramina were either missing or displaced to an abnormal location due to the absence or misplacement of its respective cranial nerve (CN). When CN development was conserved in its induction and placement, the respective foramen developed in its normal location albeit with abnormal gross anatomical features, as seen in the facial nerve (CNVII) and the internal acoustic meatus. More anteriorly localized CNs and their foramina were absent or heavily disrupted compared with posterior ones. The severe malformations exhibited in the cranial fossae, orbital region, pituitary gland and sella turcica highlight the crucial involvement of transcription factors such as TGIF, which is located on chromosome 18 and contributes to neural patterning, in the proper development of neural and cranial structures. Our study of a T18 specimen emphasizes the intricate interplay between bone and brain development in midline craniofacial abnormalities in general. © 2015 Anatomical Society.

Complex Networks in Psychological Models

NASA Astrophysics Data System (ADS)

Wedemann, R. S.; Carvalho, L. S. A. V. D.; Donangelo, R.

We develop schematic, self-organizing, neural-network models to describe mechanisms associated with mental processes, by a neurocomputational substrate. These models are examples of real world complex networks with interesting general topological structures. Considering dopaminergic signal-to-noise neuronal modulation in the central nervous system, we propose neural network models to explain development of cortical map structure and dynamics of memory access, and unify different mental processes into a single neurocomputational substrate. Based on our neural network models, neurotic behavior may be understood as an associative memory process in the brain, and the linguistic, symbolic associative process involved in psychoanalytic working-through can be mapped onto a corresponding process of reconfiguration of the neural network. The models are illustrated through computer simulations, where we varied dopaminergic modulation and observed the self-organizing emergent patterns at the resulting semantic map, interpreting them as different manifestations of mental functioning, from psychotic through to normal and neurotic behavior, and creativity.

Simulating the effect of muscle weakness and contracture on neuromuscular control of normal gait in children.

PubMed

Fox, Aaron S; Carty, Christopher P; Modenese, Luca; Barber, Lee A; Lichtwark, Glen A

2018-03-01

Altered neural control of movement and musculoskeletal deficiencies are common in children with spastic cerebral palsy (SCP), with muscle weakness and contracture commonly experienced. Both neural and musculoskeletal deficiencies are likely to contribute to abnormal gait, such as equinus gait (toe-walking), in children with SCP. However, it is not known whether the musculoskeletal deficiencies prevent normal gait or if neural control could be altered to achieve normal gait. This study examined the effect of simulated muscle weakness and contracture of the major plantarflexor/dorsiflexor muscles on the neuromuscular requirements for achieving normal walking gait in children. Initial muscle-driven simulations of walking with normal musculoskeletal properties by typically developing children were undertaken. Additional simulations with altered musculoskeletal properties were then undertaken; with muscle weakness and contracture simulated by reducing the maximum isometric force and tendon slack length, respectively, of selected muscles. Muscle activations and forces required across all simulations were then compared via waveform analysis. Maintenance of normal gait appeared robust to muscle weakness in isolation, with increased activation of weakened muscles the major compensatory strategy. With muscle contracture, reduced activation of the plantarflexors was required across the mid-portion of stance suggesting a greater contribution from passive forces. Increased activation and force during swing was also required from the tibialis anterior to counteract the increased passive forces from the simulated dorsiflexor muscle contracture. Improvements in plantarflexor and dorsiflexor motor function and muscle strength, concomitant with reductions in plantarflexor muscle stiffness may target the deficits associated with SCP that limit normal gait. Copyright © 2018 Elsevier B.V. All rights reserved.

Asymmetric segregation of the double-stranded RNA binding protein Staufen2 during mammalian neural stem cell divisions promotes lineage progression.

PubMed

Kusek, Gretchen; Campbell, Melissa; Doyle, Frank; Tenenbaum, Scott A; Kiebler, Michael; Temple, Sally

2012-10-05

Asymmetric cell divisions are a fundamental feature of neural development, and misregulation can lead to brain abnormalities or tumor formation. During an asymmetric cell division, molecular determinants are segregated preferentially into one daughter cell to specify its fate. An important goal is to identify the asymmetric determinants in neural progenitor cells, which could be tumor suppressors or inducers of specific neural fates. Here, we show that the double-stranded RNA-binding protein Stau2 is distributed asymmetrically during progenitor divisions in the developing mouse cortex, preferentially segregating into the Tbr2(+) neuroblast daughter, taking with it a subset of RNAs. Knockdown of Stau2 stimulates differentiation and overexpression produces periventricular neuronal masses, demonstrating its functional importance for normal cortical development. We immunoprecipitated Stau2 to examine its cargo mRNAs, and found enrichment for known asymmetric and basal cell determinants, such as Trim32, and identified candidates, including a subset involved in primary cilium function. Copyright © 2012 Elsevier Inc. All rights reserved.

Asymmetric Segregation of the Double-Stranded RNA Binding Protein Staufen2 during Mammalian Neural Stem Cell Divisions Promotes Lineage Progression

PubMed Central

Kusek, Gretchen; Campbell, Melissa; Doyle, Frank; Tenenbaum, Scott A.; Kiebler, Michael; Temple, Sally

2012-01-01

Summary Asymmetric cell divisions are a fundamental feature of neural development, and misregulation can lead to brain abnormalities or tumor formation. During an asymmetric cell division, molecular determinants are segregated preferentially into one daughter cell to specify its fate. An important goal is to identify the asymmetric determinants in neural progenitor cells, which could be tumor suppressors or inducers of specific neural fates. Here we show that the double-stranded RNA-binding protein Stau2 is distributed asymmetrically during progenitor divisions in the developing mouse cortex, preferentially segregating into the Tbr2+ neuroblast daughter, taking with it a sub-set of RNAs. Knockdown of Stau2 stimulates differentiation and over-expression produces periventricular neuronal masses, demonstrating its functional importance for normal cortical development. We immunoprecipitated Stau2 to examine its cargo mRNAs, and found enrichment for known asymmetric and basal cell determinants, such as Trim32, and identified novel candidates, including a subset involved in primary cilium function. PMID:22902295

EXTRAPOLATION FROM IN VITRO MECHANISMS TO IN VIVO EFFECTS FOR DEVELOPMENTAL NEUROTOXICOLOGY.

EPA Science Inventory

Processes that are critical to development of the nervous system can be altered by both genetic and epigenetic factors. Developmental exposure to neurotoxicants can alter these processes and lead to perturbation of normal neural development. As numerous processes occur in tande...

Male Killing Spiroplasma Preferentially Disrupts Neural Development in the Drosophila melanogaster Embryo

PubMed Central

Martin, Jennifer; Chong, Trisha; Ferree, Patrick M.

2013-01-01

Male killing bacteria such as Spiroplasma are widespread pathogens of numerous arthropods including Drosophila melanogaster. These maternally transmitted bacteria can bias host sex ratios toward the female sex in order to ‘selfishly’ enhance bacterial transmission. However, little is known about the specific means by which these pathogens disrupt host development in order to kill males. Here we show that a male-killing Spiroplasma strain severely disrupts nervous tissue development in male but not female D. melanogaster embryos. The neuroblasts, or neuron progenitors, form properly and their daughter cells differentiate into neurons of the ventral nerve chord. However, the neurons fail to pack together properly and they produce highly abnormal axons. In contrast, non-neural tissue, such as mesoderm, and body segmentation appear normal during this time, although the entire male embryo becomes highly abnormal during later stages. Finally, we found that Spiroplasma is altogether absent from the neural tissue but localizes within the gut and the epithelium immediately surrounding the neural tissue, suggesting that the bacterium secretes a toxin that affects neural tissue development across tissue boundaries. Together these findings demonstrate the unique ability of this insect pathogen to preferentially affect development of a specific embryonic tissue to induce male killing. PMID:24236124

Amigo adhesion protein regulates development of neural circuits in zebrafish brain.

PubMed

Zhao, Xiang; Kuja-Panula, Juha; Sundvik, Maria; Chen, Yu-Chia; Aho, Vilma; Peltola, Marjaana A; Porkka-Heiskanen, Tarja; Panula, Pertti; Rauvala, Heikki

2014-07-18

The Amigo protein family consists of three transmembrane proteins characterized by six leucine-rich repeat domains and one immunoglobulin-like domain in their extracellular moieties. Previous in vitro studies have suggested a role as homophilic adhesion molecules in brain neurons, but the in vivo functions remain unknown. Here we have cloned all three zebrafish amigos and show that amigo1 is the predominant family member expressed during nervous system development in zebrafish. Knockdown of amigo1 expression using morpholino oligonucleotides impairs the formation of fasciculated tracts in early fiber scaffolds of brain. A similar defect in fiber tract development is caused by mRNA-mediated expression of the Amigo1 ectodomain that inhibits adhesion mediated by the full-length protein. Analysis of differentiated neural circuits reveals defects in the catecholaminergic system. At the behavioral level, the disturbed formation of neural circuitry is reflected in enhanced locomotor activity and in the inability of the larvae to perform normal escape responses. We suggest that Amigo1 is essential for the development of neural circuits of zebrafish, where its mechanism involves homophilic interactions within the developing fiber tracts and regulation of the Kv2.1 potassium channel to form functional neural circuitry that controls locomotion. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

A comparative study of a theoretical neural net model with MEG data from epileptic patients and normal individuals.

PubMed

Kotini, A; Anninos, P; Anastasiadis, A N; Tamiolakis, D

2005-09-07

The aim of this study was to compare a theoretical neural net model with MEG data from epileptic patients and normal individuals. Our experimental study population included 10 epilepsy sufferers and 10 healthy subjects. The recordings were obtained with a one-channel biomagnetometer SQUID in a magnetically shielded room. Using the method of x2-fitting it was found that the MEG amplitudes in epileptic patients and normal subjects had Poisson and Gauss distributions respectively. The Poisson connectivity derived from the theoretical neural model represents the state of epilepsy, whereas the Gauss connectivity represents normal behavior. The MEG data obtained from epileptic areas had higher amplitudes than the MEG from normal regions and were comparable with the theoretical magnetic fields from Poisson and Gauss distributions. Furthermore, the magnetic field derived from the theoretical model had amplitudes in the same order as the recorded MEG from the 20 participants. The approximation of the theoretical neural net model with real MEG data provides information about the structure of the brain function in epileptic and normal states encouraging further studies to be conducted.

Atypical neural synchronization to speech envelope modulations in dyslexia.

PubMed

De Vos, Astrid; Vanvooren, Sophie; Vanderauwera, Jolijn; Ghesquière, Pol; Wouters, Jan

2017-01-01

A fundamental deficit in the synchronization of neural oscillations to temporal information in speech could underlie phonological processing problems in dyslexia. In this study, the hypothesis of a neural synchronization impairment is investigated more specifically as a function of different neural oscillatory bands and temporal information rates in speech. Auditory steady-state responses to 4, 10, 20 and 40Hz modulations were recorded in normal reading and dyslexic adolescents to measure neural synchronization of theta, alpha, beta and low-gamma oscillations to syllabic and phonemic rate information. In comparison to normal readers, dyslexic readers showed reduced non-synchronized theta activity, reduced synchronized alpha activity and enhanced synchronized beta activity. Positive correlations between alpha synchronization and phonological skills were found in normal readers, but were absent in dyslexic readers. In contrast, dyslexic readers exhibited positive correlations between beta synchronization and phonological skills. Together, these results suggest that auditory neural synchronization of alpha and beta oscillations is atypical in dyslexia, indicating deviant neural processing of both syllabic and phonemic rate information. Impaired synchronization of alpha oscillations in particular demonstrated to be the most prominent neural anomaly possibly hampering speech and phonological processing in dyslexic readers. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuroblastoma pathogenesis: deregulation of embryonic neural crest development.

PubMed

Tomolonis, Julie A; Agarwal, Saurabh; Shohet, Jason M

2018-05-01

Neuroblastoma (NB) is an aggressive pediatric cancer that originates from neural crest tissues of the sympathetic nervous system. NB is highly heterogeneous both from a clinical and a molecular perspective. Clinically, this cancer represents a wide range of phenotypes ranging from spontaneous regression of 4S disease to unremitting treatment-refractory progression and death of high-risk metastatic disease. At a cellular level, the heterogeneous behavior of NB likely arises from an arrest and deregulation of normal neural crest development. In the present review, we summarize our current knowledge of neural crest development as it relates to pathways promoting 'stemness' and how deregulation may contribute to the development of tumor-initiating CSCs. There is an emerging consensus that such tumor subpopulations contribute to the evolution of drug resistance, metastasis and relapse in other equally aggressive malignancies. As relapsed, refractory disease remains the primary cause of death for neuroblastoma, the identification and targeting of CSCs or other primary drivers of tumor progression remains a critical, clinically significant goal for neuroblastoma. We will critically review recent and past evidence in the literature supporting the concept of CSCs as drivers of neuroblastoma pathogenesis.

Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Guang; Li, Yan; Wang, Xiao-yu

2013-05-01

Formation of the neural tube is the morphological hallmark for development of the embryonic central nervous system (CNS). Therefore, neural tube development is a crucial step in the neurulation process. Slit/Robo signaling was initially identified as a chemo-repellent that regulated axon growth cone elongation, but its role in controlling neural tube development is currently unknown. To address this issue, we investigated Slit/Robo1 signaling in the development of chick neCollege of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH, UKural tube and transgenic mice over-expressing Slit2. We disrupted Slit/Robo1 signaling by injecting R5 monoclonal antibodies into HH10 neural tubes tomore » block the Robo1 receptor. This inhibited the normal development of the ventral body curvature and caused the spinal cord to curl up into a S-shape. Next, Slit/Robo1 signaling on one half-side of the chick embryo neural tube was disturbed by electroporation in ovo. We found that the morphology of the neural tube was dramatically abnormal after we interfered with Slit/Robo1 signaling. Furthermore, we established that silencing Robo1 inhibited cell proliferation while over-expressing Robo1 enhanced cell proliferation. We also investigated the effects of altering Slit/Robo1 expression on Sonic Hedgehog (Shh) and Pax7 expression in the developing neural tube. We demonstrated that over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1{sup +} migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug{sup +} pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1{sup +} migrating NCCs but reduced Pax7 expression and fewer Slug{sup +} pre-migratory NCCs were observed. In conclusion, we propose that Slit/Robo1 signaling is involved in regulating neural tube development by tightly coordinating cell proliferation and differentiation during neurulation. - Highlights: ► The role of Slit/Robo1 signaling was investigated with chick and mouse models. ► Disturbance of Slit/Robo1 signaling resulted in neural tube defects. ► Slit/Robo1 signaling regulated the proliferation of neural tube cells. ► Slit/Robo1 signaling modulated the differentiation of neural tube cells. ► Slit/Robo1 signaling balanced the proliferation and differentiation of neural tube.« less

Neural Markers of the Development of Executive Function: Relevance for Education

PubMed Central

Shanmugan, Sheila; Satterthwaite, Theodore D.

2016-01-01

Executive functions are involved in the development of academic skills and are critical for functioning in school settings. The relevance of executive functions to education begins early and continues throughout development, with clear impact on achievement. Diverse efforts increasingly suggest ways in which facilitating development of executive function may be used to improve academic performance. Such interventions seek to alter the trajectory of executive development, which exhibits a protracted course of maturation that stretches into young adulthood. As such, it may be useful to understand how the executive system develops normally and abnormally in order to tailor interventions within educational settings. Here we review recent work investigating the neural basis for executive development during childhood and adolescence. PMID:27182537

Regulation of endogenous neural stem/progenitor cells for neural repair—factors that promote neurogenesis and gliogenesis in the normal and damaged brain

PubMed Central

Christie, Kimberly J.; Turnley, Ann M.

2012-01-01

Neural stem/precursor cells in the adult brain reside in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. These cells primarily generate neuroblasts that normally migrate to the olfactory bulb (OB) and the dentate granule cell layer respectively. Following brain damage, such as traumatic brain injury, ischemic stroke or in degenerative disease models, neural precursor cells from the SVZ in particular, can migrate from their normal route along the rostral migratory stream (RMS) to the site of neural damage. This neural precursor cell response to neural damage is mediated by release of endogenous factors, including cytokines and chemokines produced by the inflammatory response at the injury site, and by the production of growth and neurotrophic factors. Endogenous hippocampal neurogenesis is frequently also directly or indirectly affected by neural damage. Administration of a variety of factors that regulate different aspects of neural stem/precursor biology often leads to improved functional motor and/or behavioral outcomes. Such factors can target neural stem/precursor proliferation, survival, migration and differentiation into appropriate neuronal or glial lineages. Newborn cells also need to subsequently survive and functionally integrate into extant neural circuitry, which may be the major bottleneck to the current therapeutic potential of neural stem/precursor cells. This review will cover the effects of a range of intrinsic and extrinsic factors that regulate neural stem/precursor cell functions. In particular it focuses on factors that may be harnessed to enhance the endogenous neural stem/precursor cell response to neural damage, highlighting those that have already shown evidence of preclinical effectiveness and discussing others that warrant further preclinical investigation. PMID:23346046

Indian hedgehog signaling from endothelial cells is required for sclera and retinal pigment epithelium development in the mouse eye.

PubMed

Dakubo, Gabriel D; Mazerolle, Chantal; Furimsky, Marosh; Yu, Chuan; St-Jacques, Benoit; McMahon, Andrew P; Wallace, Valerie A

2008-08-01

The development of extraocular orbital structures, in particular the choroid and sclera, is regulated by a complex series of interactions between neuroectoderm, neural crest and mesoderm derivatives, although in many instances the signals that mediate these interactions are not known. In this study we have investigated the function of Indian hedgehog (Ihh) in the developing mammalian eye. We show that Ihh is expressed in a population of non-pigmented cells located in the developing choroid adjacent to the RPE. The analysis of Hh mutant mice demonstrates that the RPE and developing scleral mesenchyme are direct targets of Ihh signaling and that Ihh is required for the normal pigmentation pattern of the RPE and the condensation of mesenchymal cells to form the sclera. Our findings also indicate that Ihh signals indirectly to promote proliferation and photoreceptor specification in the neural retina. This study identifies Ihh as a novel choroid-derived signal that regulates RPE, sclera and neural retina development.

Fault detection and diagnosis using neural network approaches

NASA Technical Reports Server (NTRS)

Kramer, Mark A.

1992-01-01

Neural networks can be used to detect and identify abnormalities in real-time process data. Two basic approaches can be used, the first based on training networks using data representing both normal and abnormal modes of process behavior, and the second based on statistical characterization of the normal mode only. Given data representative of process faults, radial basis function networks can effectively identify failures. This approach is often limited by the lack of fault data, but can be facilitated by process simulation. The second approach employs elliptical and radial basis function neural networks and other models to learn the statistical distributions of process observables under normal conditions. Analytical models of failure modes can then be applied in combination with the neural network models to identify faults. Special methods can be applied to compensate for sensor failures, to produce real-time estimation of missing or failed sensors based on the correlations codified in the neural network.

A zinc finger protein Zfp521 directs neural differentiation and beyond

PubMed Central

2011-01-01

Neural induction is largely considered a default process, whereas little is known about intrinsic factors that drive neural differentiation. Kamiya and colleagues now demonstrate that a transcription factor, Zfp521, is capable of directing embryonic stem (ES) cells into neural progenitors. They discovered that Zfp521 transcripts were enriched in early neural lineage of ES cell differentiation. Forced expression of Zfp521 turned ES cells into neural progenitors in culture conditions that would normally inhibit neural differentiation. Zfp521 was expressed in mouse embryos during gastrulation. The protein was shown to associate with a co-activator p300 and directly induce expression of early neural genes. Knockdown of the Zfp521 by shRNA halted cells at the epiblast stage and suppressed neural differentiation. Zfp521 is a nuclear protein with 30 Krüppel-like zinc fingers mediating multiple protein-protein interactions, and regulates transcription in diverse tissues and organs. The protein promotes proliferation, delays differentiation and reduces apoptosis. The findings by Kamiya and colleagues that Zfp521 directs and sustains early neural differentiation now opens up a series of studies to investigate roles of Zfp521 in stem cells and brain development of mice and men. PMID:21539723

Condition monitoring of 3G cellular networks through competitive neural models.

PubMed

Barreto, Guilherme A; Mota, João C M; Souza, Luis G M; Frota, Rewbenio A; Aguayo, Leonardo

2005-09-01

We develop an unsupervised approach to condition monitoring of cellular networks using competitive neural algorithms. Training is carried out with state vectors representing the normal functioning of a simulated CDMA2000 network. Once training is completed, global and local normality profiles (NPs) are built from the distribution of quantization errors of the training state vectors and their components, respectively. The global NP is used to evaluate the overall condition of the cellular system. If abnormal behavior is detected, local NPs are used in a component-wise fashion to find abnormal state variables. Anomaly detection tests are performed via percentile-based confidence intervals computed over the global and local NPs. We compared the performance of four competitive algorithms [winner-take-all (WTA), frequency-sensitive competitive learning (FSCL), self-organizing map (SOM), and neural-gas algorithm (NGA)] and the results suggest that the joint use of global and local NPs is more efficient and more robust than current single-threshold methods.

Application of a neural network as a potential aid in predicting NTF pump failure

NASA Technical Reports Server (NTRS)

Rogers, James L.; Hill, Jeffrey S.; Lamarsh, William J., II; Bradley, David E.

1993-01-01

The National Transonic Facility has three centrifugal multi-stage pumps to supply liquid nitrogen to the wind tunnel. Pump reliability is critical to facility operation and test capability. A highly desirable goal is to be able to detect a pump rotating component problem as early as possible during normal operation and avoid serious damage to other pump components. If a problem is detected before serious damage occurs, the repair cost and downtime could be reduced significantly. A neural network-based tool was developed for monitoring pump performance and aiding in predicting pump failure. Once trained, neural networks can rapidly process many combinations of input values other than those used for training to approximate previously unknown output values. This neural network was applied to establish relationships among the critical frequencies and aid in predicting failures. Training pairs were developed from frequency scans from typical tunnel operations. After training, various combinations of critical pump frequencies were propagated through the neural network. The approximated output was used to create a contour plot depicting the relationships of the input frequencies to the output pump frequency.

Improving Neural Recording Technology at the Nanoscale

NASA Astrophysics Data System (ADS)

Ferguson, John Eric

Neural recording electrodes are widely used to study normal brain function (e.g., learning, memory, and sensation) and abnormal brain function (e.g., epilepsy, addiction, and depression) and to interface with the nervous system for neuroprosthetics. With a deep understanding of the electrode interface at the nanoscale and the use of novel nanofabrication processes, neural recording electrodes can be designed that surpass previous limits and enable new applications. In this thesis, I will discuss three projects. In the first project, we created an ultralow-impedance electrode coating by controlling the nanoscale texture of electrode surfaces. In the second project, we developed a novel nanowire electrode for long-term intracellular recordings. In the third project, we created a means of wirelessly communicating with ultra-miniature, implantable neural recording devices. The techniques developed for these projects offer significant improvements in the quality of neural recordings. They can also open the door to new types of experiments and medical devices, which can lead to a better understanding of the brain and can enable novel and improved tools for clinical applications.

Neonatal ghrelin programs development of hypothalamic feeding circuits

PubMed Central

Steculorum, Sophie M.; Collden, Gustav; Coupe, Berengere; Croizier, Sophie; Lockie, Sarah; Andrews, Zane B.; Jarosch, Florian; Klussmann, Sven; Bouret, Sebastien G.

2015-01-01

A complex neural network regulates body weight and energy balance, and dysfunction in the communication between the gut and this neural network is associated with metabolic diseases, such as obesity. The stomach-derived hormone ghrelin stimulates appetite through interactions with neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we evaluated the physiological and neurobiological contribution of ghrelin during development by specifically blocking ghrelin action during early postnatal development in mice. Ghrelin blockade in neonatal mice resulted in enhanced ARH neural projections and long-term metabolic effects, including increased body weight, visceral fat, and blood glucose levels and decreased leptin sensitivity. In addition, chronic administration of ghrelin during postnatal life impaired the normal development of ARH projections and caused metabolic dysfunction. Consistent with these observations, direct exposure of postnatal ARH neuronal explants to ghrelin blunted axonal growth and blocked the neurotrophic effect of the adipocyte-derived hormone leptin. Moreover, chronic ghrelin exposure in neonatal mice also attenuated leptin-induced STAT3 signaling in ARH neurons. Collectively, these data reveal that ghrelin plays an inhibitory role in the development of hypothalamic neural circuits and suggest that proper expression of ghrelin during neonatal life is pivotal for lifelong metabolic regulation. PMID:25607843

Medical Concept Normalization in Social Media Posts with Recurrent Neural Networks.

PubMed

Tutubalina, Elena; Miftahutdinov, Zulfat; Nikolenko, Sergey; Malykh, Valentin

2018-06-12

Text mining of scientific libraries and social media has already proven itself as a reliable tool for drug repurposing and hypothesis generation. The task of mapping a disease mention to a concept in a controlled vocabulary, typically to the standard thesaurus in the Unified Medical Language System (UMLS), is known as medical concept normalization. This task is challenging due to the differences in the use of medical terminology between health care professionals and social media texts coming from the lay public. To bridge this gap, we use sequence learning with recurrent neural networks and semantic representation of one- or multi-word expressions: we develop end-to-end architectures directly tailored to the task, including bidirectional Long Short-Term Memory, Gated Recurrent Units with an attention mechanism, and additional semantic similarity features based on UMLS. Our evaluation against a standard benchmark shows that recurrent neural networks improve results over an effective baseline for classification based on convolutional neural networks. A qualitative examination of mentions discovered in a dataset of user reviews collected from popular online health information platforms as well as a quantitative evaluation both show improvements in the semantic representation of health-related expressions in social media. Copyright © 2018. Published by Elsevier Inc.

Development of a brain monitoring system for multimodality investigation in awake rats.

PubMed

Limnuson, Kanokwan; Narayan, Raj K; Chiluwal, Amrit; Bouton, Chad; Ping Wang; Chunyan Li

2016-08-01

Multimodal brain monitoring is an important approach to gain insight into brain function, modulation, and pathology. We have developed a unique micromachined neural probe capable of real-time continuous monitoring of multiple physiological, biochemical and electrophysiological variables. However, to date, it has only been used in anesthetized animals due to a lack of an appropriate interface for awake animals. We have developed a versatile headstage for recording the small neural signal and bridging the sensors to the remote sensing units for multimodal brain monitoring in awake rats. The developed system has been successfully validated in awake rats by simultaneously measuring four cerebral variables: electrocorticography, oxygen tension, temperature and cerebral blood flow. Reliable signal recordings were obtained with minimal artifacts from movement and environmental noise. For the first time, multiple variables of cerebral function and metabolism were simultaneously recorded from awake rats using a single neural probe. The system is envisioned for studying the effects of pharmacologic treatments, mapping the development of central nervous system diseases, and better understanding normal cerebral physiology.

Deconstructing Interocular Suppression: Attention and Divisive Normalization

PubMed Central

Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J.

2015-01-01

In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression. PMID:26517321

Deconstructing Interocular Suppression: Attention and Divisive Normalization.

PubMed

Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J

2015-10-01

In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression.

A cortical neural prosthesis for restoring and enhancing memory

NASA Astrophysics Data System (ADS)

Berger, Theodore W.; Hampson, Robert E.; Song, Dong; Goonawardena, Anushka; Marmarelis, Vasilis Z.; Deadwyler, Sam A.

2011-08-01

A primary objective in developing a neural prosthesis is to replace neural circuitry in the brain that no longer functions appropriately. Such a goal requires artificial reconstruction of neuron-to-neuron connections in a way that can be recognized by the remaining normal circuitry, and that promotes appropriate interaction. In this study, the application of a specially designed neural prosthesis using a multi-input/multi-output (MIMO) nonlinear model is demonstrated by using trains of electrical stimulation pulses to substitute for MIMO model derived ensemble firing patterns. Ensembles of CA3 and CA1 hippocampal neurons, recorded from rats performing a delayed-nonmatch-to-sample (DNMS) memory task, exhibited successful encoding of trial-specific sample lever information in the form of different spatiotemporal firing patterns. MIMO patterns, identified online and in real-time, were employed within a closed-loop behavioral paradigm. Results showed that the model was able to predict successful performance on the same trial. Also, MIMO model-derived patterns, delivered as electrical stimulation to the same electrodes, improved performance under normal testing conditions and, more importantly, were capable of recovering performance when delivered to animals with ensemble hippocampal activity compromised by pharmacologic blockade of synaptic transmission. These integrated experimental-modeling studies show for the first time that, with sufficient information about the neural coding of memories, a neural prosthesis capable of real-time diagnosis and manipulation of the encoding process can restore and even enhance cognitive, mnemonic processes.

Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells to cause a loss of forebrain in Xenopus embryos

NASA Technical Reports Server (NTRS)

Fredieu, J. R.; Cui, Y.; Maier, D.; Danilchik, M. V.; Christian, J. L.

1997-01-01

When Xenopus gastrulae are made to misexpress Xwnt-8, or are exposed to lithium ions, they develop with a loss of anterior structures. In the current study, we have characterized the neural defects produced by either Xwnt-8 or lithium and have examined potential cellular mechanisms underlying this anterior truncation. We find that the primary defect in embryos exposed to lithium at successively earlier stages during gastrulation is a progressive rostral to caudal deletion of the forebrain, while hindbrain and spinal regions of the CNS remain intact. Misexpression of Xwnt-8 during gastrulation produces an identical loss of forebrain. Our results demonstrate that lithium and Wnts can act upon either prospective neural ectodermal cells, or upon dorsal mesodermal cells, to cause a loss of anterior pattern. Specifically, ectodermal cells isolated from lithium- or Wnt-exposed embryos are unable to form anterior neural tissue in response to inductive signals from normal dorsal mesoderm. In addition, although dorsal mesodermal cells from lithium- or Wnt-exposed embryos are specified properly, and produce normal levels of the anterior neural inducing molecules noggin and chordin, they show a greatly reduced capacity to induce anterior neural tissue in conjugated ectoderm. Taken together, our results are consistent with a model in which Wnt- or lithium-mediated signals can induce either mesodermal or ectodermal cells to produce a dominant posteriorizing morphogen which respecifies anterior neural tissue as posterior.

Alternative neural circuitry that might be impaired in the development of Alzheimer disease.

PubMed

Avila, Jesus; Perry, George; Strange, Bryan A; Hernandez, Felix

2015-01-01

It is well established that some individuals with normal cognitive capacity have abundant senile plaques in their brains. It has been proposed that those individuals are resilient or have compensation factors to prevent cognitive decline. In this comment, we explore an alternative mechanism through which cognitive capacity is maintained. This mechanism could involve the impairment of alternative neural circuitry. Also, the proportion of molecules such as Aβ or tau protein present in different areas of the brain could be important.

Comparison of artificial intelligence classifiers for SIP attack data

NASA Astrophysics Data System (ADS)

Safarik, Jakub; Slachta, Jiri

2016-05-01

Honeypot application is a source of valuable data about attacks on the network. We run several SIP honeypots in various computer networks, which are separated geographically and logically. Each honeypot runs on public IP address and uses standard SIP PBX ports. All information gathered via honeypot is periodically sent to the centralized server. This server classifies all attack data by neural network algorithm. The paper describes optimizations of a neural network classifier, which lower the classification error. The article contains the comparison of two neural network algorithm used for the classification of validation data. The first is the original implementation of the neural network described in recent work; the second neural network uses further optimizations like input normalization or cross-entropy cost function. We also use other implementations of neural networks and machine learning classification algorithms. The comparison test their capabilities on validation data to find the optimal classifier. The article result shows promise for further development of an accurate SIP attack classification engine.

Spiking Neural Network Decoder for Brain-Machine Interfaces.

PubMed

Dethier, Julie; Gilja, Vikash; Nuyujukian, Paul; Elassaad, Shauki A; Shenoy, Krishna V; Boahen, Kwabena

2011-01-01

We used a spiking neural network (SNN) to decode neural data recorded from a 96-electrode array in premotor/motor cortex while a rhesus monkey performed a point-to-point reaching arm movement task. We mapped a Kalman-filter neural prosthetic decode algorithm developed to predict the arm's velocity on to the SNN using the Neural Engineering Framework and simulated it using Nengo , a freely available software package. A 20,000-neuron network matched the standard decoder's prediction to within 0.03% (normalized by maximum arm velocity). A 1,600-neuron version of this network was within 0.27%, and run in real-time on a 3GHz PC. These results demonstrate that a SNN can implement a statistical signal processing algorithm widely used as the decoder in high-performance neural prostheses (Kalman filter), and achieve similar results with just a few thousand neurons. Hardware SNN implementations-neuromorphic chips-may offer power savings, essential for realizing fully-implantable cortically controlled prostheses.

Neural crest contribution to the cardiovascular system.

PubMed

Brown, Christopher B; Baldwin, H Scott

2006-01-01

Normal cardiovascular development requires complex remodeling of the outflow tract and pharyngeal arch arteries to create the separate pulmonic and systemic circulations. During remodeling, the outflow tract is septated to form the ascending aorta and the pulmonary trunk. The initially symmetrical pharyngeal arch arteries are remodeled to form the aortic arch, subclavian and carotid arteries. Remodeling is mediated by a population of neural crest cells arising between the mid-otic placode and somite four called the cardiac neural crest. Cardiac neural crest cells form smooth muscle and pericytes in the great arteries, and the neurons of cardiac innervation. In addition to the physical contribution of smooth muscle to the cardiovascular system, cardiac neural crest cells also provide signals required for the maintenance and differentiation of the other cell layers in the pharyngeal apparatus. Reciprocal signaling between the cardiac neural crest cells and cardiogenic mesoderm of the secondary heart field is required for elaboration of the conotruncus and disruption in this signaling results in primary myocardial dysfunction. Cardiovascular defects attributed to the cardiac neural crest cells may reflect either cell autonomous defects in the neural crest or defects in signaling between the neural crest and adjacent cell layers.

A critical role for PDGFRα signaling in medial nasal process development.

PubMed

He, Fenglei; Soriano, Philippe

2013-01-01

The primitive face is composed of neural crest cell (NCC) derived prominences. The medial nasal processes (MNP) give rise to the upper lip and vomeronasal organ, and are essential for normal craniofacial development, but the mechanism of MNP development remains largely unknown. PDGFRα signaling is known to be critical for NCC development and craniofacial morphogenesis. In this study, we show that PDGFRα is required for MNP development by maintaining the migration of progenitor neural crest cells (NCCs) and the proliferation of MNP cells. Further investigations reveal that PI3K/Akt and Rac1 signaling mediate PDGFRα function during MNP development. We thus establish PDGFRα as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels.

Deep neural network convolution (NNC) for three-class classification of diffuse lung disease opacities in high-resolution CT (HRCT): consolidation, ground-glass opacity (GGO), and normal opacity

NASA Astrophysics Data System (ADS)

Hashimoto, Noriaki; Suzuki, Kenji; Liu, Junchi; Hirano, Yasushi; MacMahon, Heber; Kido, Shoji

2018-02-01

Consolidation and ground-glass opacity (GGO) are two major types of opacities associated with diffuse lung diseases. Accurate detection and classification of such opacities are crucially important in the diagnosis of lung diseases, but the process is subjective, and suffers from interobserver variability. Our study purpose was to develop a deep neural network convolution (NNC) system for distinguishing among consolidation, GGO, and normal lung tissue in high-resolution CT (HRCT). We developed ensemble of two deep NNC models, each of which was composed of neural network regression (NNR) with an input layer, a convolution layer, a fully-connected hidden layer, and a fully-connected output layer followed by a thresholding layer. The output layer of each NNC provided a map for the likelihood of being each corresponding lung opacity of interest. The two NNC models in the ensemble were connected in a class-selection layer. We trained our NNC ensemble with pairs of input 2D axial slices and "teaching" probability maps for the corresponding lung opacity, which were obtained by combining three radiologists' annotations. We randomly selected 10 and 40 slices from HRCT scans of 172 patients for each class as a training and test set, respectively. Our NNC ensemble achieved an area under the receiver-operating-characteristic (ROC) curve (AUC) of 0.981 and 0.958 in distinction of consolidation and GGO, respectively, from normal opacity, yielding a classification accuracy of 93.3% among 3 classes. Thus, our deep-NNC-based system for classifying diffuse lung diseases achieved high accuracies for classification of consolidation, GGO, and normal opacity.

The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line.

PubMed

Fujiwara, Yuki; Miyazaki, Wataru; Koibuchi, Noriyuki; Katoh, Takahiko

2018-01-01

Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA), which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF), an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP), and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

Neural crest-specific deletion of Ldb1 leads to cleft secondary palate with impaired palatal shelf elevation

PubMed Central

2014-01-01

Background LIM domain binding protein 1 (LDB1) is a transcriptional co-factor, which interacts with multiple transcription factors and other proteins containing LIM domains. Complete inactivation of Ldb1 in mice resulted in early embryonic lethality with severe patterning defects during gastrulation. Tissue-specific deletions using a conditional knockout allele revealed additional roles of Ldb1 in the development of the central nervous system, hematopoietic system, and limbs. The goal of the current study was to determine the importance of Ldb1 function during craniofacial development in mouse embryos. Results We generated tissue-specific Ldb1 mutants using Wnt1-Cre, which causes deletion of a floxed allele in the neural crest; neural crest-derived cells contribute to most of the mesenchyme of the developing face. All examined Wnt1-Cre;Ldb1 fl/- mutants suffered from cleft secondary palate. Therefore, we performed a series of experiments to investigate how Ldb1 regulated palate development. First, we examined the expression of Ldb1 during normal development, and found that Ldb1 was expressed broadly in the palatal mesenchyme during early stages of palate development. Second, we compared the morphology of the developing palate in control and Ldb1 mutant embryos using sections. We found that the mutant palatal shelves had abnormally blunt appearance, and failed to elevate above the tongue at the posterior domain. An in vitro head culture experiment indicated that the elevation defect was not due to interference by the tongue. Finally, in the Ldb1 mutant palatal shelves, cell proliferation was abnormal in the anterior, and the expression of Wnt5a, Pax9 and Osr2, which regulate palatal shelf elevation, was also altered. Conclusions The function of Ldb1 in the neural crest-derived palatal mesenchyme is essential for normal morphogenesis of the secondary palate. PMID:24433583

Verification and Validation of Adaptive and Intelligent Systems with Flight Test Results

NASA Technical Reports Server (NTRS)

Burken, John J.; Larson, Richard R.

2009-01-01

F-15 IFCS project goals are: a) Demonstrate Control Approaches that can Efficiently Optimize Aircraft Performance in both Normal and Failure Conditions [A] & [B] failures. b) Advance Neural Network-Based Flight Control Technology for New Aerospace Systems Designs with a Pilot in the Loop. Gen II objectives include; a) Implement and Fly a Direct Adaptive Neural Network Based Flight Controller; b) Demonstrate the Ability of the System to Adapt to Simulated System Failures: 1) Suppress Transients Associated with Failure; 2) Re-Establish Sufficient Control and Handling of Vehicle for Safe Recovery. c) Provide Flight Experience for Development of Verification and Validation Processes for Flight Critical Neural Network Software.

Alpha, delta and theta rhythms in a neural net model. Comparison with MEG data.

PubMed

Kotini, A; Anninos, P

2016-01-07

The aim of this study is to provide information regarding the comparison of a neural model to MEG measurements. Our study population consisted of 10 epileptic patients and 10 normal subjects. The epileptic patients had high MEG amplitudes characterized with θ (4-7 Hz) or δ (2-3 Hz) rhythms and absence of α-rhythm (8-13 Hz). The statistical analysis of such activities corresponded to Poisson distribution. Conversely, the MEG from normal subjects had low amplitudes, higher frequencies and presence of α-rhythm (8-13 Hz). Such activities were not synchronized and their distributions were Gauss. These findings were in agreement with our theoretical neural model. The comparison of the neural network with MEG data provides information about the status of brain function in epileptic and normal states. Copyright © 2015 Elsevier Ltd. All rights reserved.

The impact of neurotechnology on rehabilitation.

PubMed

Berger, Theodore W; Gerhardt, Greg; Liker, Mark A; Soussou, Walid

2008-01-01

This paper present results of a multi-disciplinary project that is developing a microchip-based neural prosthesis for the hippocampus, a region of the brain responsible for the formation of long-term memories. Damage to the hippocampus is frequently associated with epilepsy, stroke, and dementia (Alzheimer's disease) and is considered to underlie the memory deficits related to these neurological conditions. The essential goals of the multi-laboratory effort include: (1) experimental study of neuron and neural network function--how does the hippocampus encode information? (2) formulation of biologically realistic models of neural system dynamics--can that encoding process be described mathematically to realize a predictive model of how the hippocampus responds to any event? (3) microchip implementation of neural system models--can the mathematical model be realized as a set of electronic circuits to achieve parallel processing, rapid computational speed, and miniaturization? and (4) creation of hybrid neuron-silicon interfaces-can structural and functional connections between electronic devices and neural tissue be achieved for long-term, bi-directional communication with the brain? By integrating solutions to these component problems, we are realizing a microchip-based model of hippocampal nonlinear dynamics that can perform the same function as part of the hippocampus. Through bi-directional communication with other neural tissue that normally provides the inputs and outputs to/from a damaged hippocampal area, the biomimetic model could serve as a neural prosthesis. A proof-of-concept will be presented in which the CA3 region of the hippocampal slice is surgically removed and is replaced by a microchip model of CA3 nonlinear dynamics--the "hybrid" hippocampal circuit displays normal physiological properties. How the work in brain slices is being extended to behaving animals also will be described.

Genetic reprogramming of human amniotic cells with episomal vectors: neural rosettes as sentinels in candidate selection for validation assays.

PubMed

Wilson, Patricia G; Payne, Tiffany

2014-01-01

The promise of genetic reprogramming has prompted initiatives to develop banks of induced pluripotent stem cells (iPSCs) from diverse sources. Sentinel assays for pluripotency could maximize available resources for generating iPSCs. Neural rosettes represent a primitive neural tissue that is unique to differentiating PSCs and commonly used to identify derivative neural/stem progenitors. Here, neural rosettes were used as a sentinel assay for pluripotency in selection of candidates to advance to validation assays. Candidate iPSCs were generated from independent populations of amniotic cells with episomal vectors. Phase imaging of living back up cultures showed neural rosettes in 2 of the 5 candidate populations. Rosettes were immunopositive for the Sox1, Sox2, Pax6 and Pax7 transcription factors that govern neural development in the earliest stage of development and for the Isl1/2 and Otx2 transcription factors that are expressed in the dorsal and ventral domains, respectively, of the neural tube in vivo. Dissociation of rosettes produced cultures of differentiation competent neural/stem progenitors that generated immature neurons that were immunopositive for βIII-tubulin and glia that were immunopositive for GFAP. Subsequent validation assays of selected candidates showed induced expression of endogenous pluripotency genes, epigenetic modification of chromatin and formation of teratomas in immunodeficient mice that contained derivatives of the 3 embryonic germ layers. Validated lines were vector-free and maintained a normal karyotype for more than 60 passages. The credibility of rosette assembly as a sentinel assay for PSCs is supported by coordinate loss of nuclear-localized pluripotency factors Oct4 and Nanog in neural rosettes that emerge spontaneously in cultures of self-renewing validated lines. Taken together, these findings demonstrate value in neural rosettes as sentinels for pluripotency and selection of promising candidates for advance to validation assays.

Genetic reprogramming of human amniotic cells with episomal vectors: neural rosettes as sentinels in candidate selection for validation assays

PubMed Central

Payne, Tiffany

2014-01-01

The promise of genetic reprogramming has prompted initiatives to develop banks of induced pluripotent stem cells (iPSCs) from diverse sources. Sentinel assays for pluripotency could maximize available resources for generating iPSCs. Neural rosettes represent a primitive neural tissue that is unique to differentiating PSCs and commonly used to identify derivative neural/stem progenitors. Here, neural rosettes were used as a sentinel assay for pluripotency in selection of candidates to advance to validation assays. Candidate iPSCs were generated from independent populations of amniotic cells with episomal vectors. Phase imaging of living back up cultures showed neural rosettes in 2 of the 5 candidate populations. Rosettes were immunopositive for the Sox1, Sox2, Pax6 and Pax7 transcription factors that govern neural development in the earliest stage of development and for the Isl1/2 and Otx2 transcription factors that are expressed in the dorsal and ventral domains, respectively, of the neural tube in vivo. Dissociation of rosettes produced cultures of differentiation competent neural/stem progenitors that generated immature neurons that were immunopositive for βIII-tubulin and glia that were immunopositive for GFAP. Subsequent validation assays of selected candidates showed induced expression of endogenous pluripotency genes, epigenetic modification of chromatin and formation of teratomas in immunodeficient mice that contained derivatives of the 3 embryonic germ layers. Validated lines were vector-free and maintained a normal karyotype for more than 60 passages. The credibility of rosette assembly as a sentinel assay for PSCs is supported by coordinate loss of nuclear-localized pluripotency factors Oct4 and Nanog in neural rosettes that emerge spontaneously in cultures of self-renewing validated lines. Taken together, these findings demonstrate value in neural rosettes as sentinels for pluripotency and selection of promising candidates for advance to validation assays. PMID:25426336

Towards intelligent diagnostic system employing integration of mathematical and engineering model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isa, Nor Ashidi Mat

The development of medical diagnostic system has been one of the main research fields during years. The goal of the medical diagnostic system is to place a nosological system that could ease the diagnostic evaluation normally performed by scientists and doctors. Efficient diagnostic evaluation is essentials and requires broad knowledge in order to improve conventional diagnostic system. Several approaches on developing the medical diagnostic system have been designed and tested since the earliest 60s. Attempts on improving their performance have been made which utilizes the fields of artificial intelligence, statistical analyses, mathematical model and engineering theories. With the availability ofmore » the microcomputer and software development as well as the promising aforementioned fields, medical diagnostic prototypes could be developed. In general, the medical diagnostic system consists of several stages, namely the 1) data acquisition, 2) feature extraction, 3) feature selection, and 4) classifications stages. Data acquisition stage plays an important role in converting the inputs measured from the real world physical conditions to the digital numeric values that can be manipulated by the computer system. One of the common medical inputs could be medical microscopic images, radiographic images, magnetic resonance image (MRI) as well as medical signals such as electrocardiogram (ECG) and electroencephalogram (EEG). Normally, the scientist or doctors have to deal with myriad of data and redundant to be processed. In order to reduce the complexity of the diagnosis process, only the significant features of the raw data such as peak value of the ECG signal or size of lesion in the mammogram images will be extracted and considered in the subsequent stages. Mathematical models and statistical analyses will be performed to select the most significant features to be classified. The statistical analyses such as principal component analysis and discriminant analysis as well as mathematical model of clustering technique have been widely used in developing the medical diagnostic systems. The selected features will be classified using mathematical models that embedded engineering theory such as artificial intelligence, support vector machine, neural network and fuzzy-neuro system. These classifiers will provide the diagnostic results without human intervention. Among many publishable researches, several prototypes have been developed namely NeuralPap, Neural Mammo, and Cervix Kit. The former system (NeuralPap) is an automatic intelligent diagnostic system for classifying and distinguishing between the normal and cervical cancerous cells. Meanwhile, the Cervix Kit is a portable Field-programmable gate array (FPGA)-based cervical diagnostic kit that could automatically diagnose the cancerous cell based on the images obtained during sampling test. Besides the cervical diagnostic system, the Neural Mammo system is developed to specifically aid the diagnosis of breast cancer using a fine needle aspiration image.« less

Towards intelligent diagnostic system employing integration of mathematical and engineering model

NASA Astrophysics Data System (ADS)

Isa, Nor Ashidi Mat

2015-05-01

The development of medical diagnostic system has been one of the main research fields during years. The goal of the medical diagnostic system is to place a nosological system that could ease the diagnostic evaluation normally performed by scientists and doctors. Efficient diagnostic evaluation is essentials and requires broad knowledge in order to improve conventional diagnostic system. Several approaches on developing the medical diagnostic system have been designed and tested since the earliest 60s. Attempts on improving their performance have been made which utilizes the fields of artificial intelligence, statistical analyses, mathematical model and engineering theories. With the availability of the microcomputer and software development as well as the promising aforementioned fields, medical diagnostic prototypes could be developed. In general, the medical diagnostic system consists of several stages, namely the 1) data acquisition, 2) feature extraction, 3) feature selection, and 4) classifications stages. Data acquisition stage plays an important role in converting the inputs measured from the real world physical conditions to the digital numeric values that can be manipulated by the computer system. One of the common medical inputs could be medical microscopic images, radiographic images, magnetic resonance image (MRI) as well as medical signals such as electrocardiogram (ECG) and electroencephalogram (EEG). Normally, the scientist or doctors have to deal with myriad of data and redundant to be processed. In order to reduce the complexity of the diagnosis process, only the significant features of the raw data such as peak value of the ECG signal or size of lesion in the mammogram images will be extracted and considered in the subsequent stages. Mathematical models and statistical analyses will be performed to select the most significant features to be classified. The statistical analyses such as principal component analysis and discriminant analysis as well as mathematical model of clustering technique have been widely used in developing the medical diagnostic systems. The selected features will be classified using mathematical models that embedded engineering theory such as artificial intelligence, support vector machine, neural network and fuzzy-neuro system. These classifiers will provide the diagnostic results without human intervention. Among many publishable researches, several prototypes have been developed namely NeuralPap, Neural Mammo, and Cervix Kit. The former system (NeuralPap) is an automatic intelligent diagnostic system for classifying and distinguishing between the normal and cervical cancerous cells. Meanwhile, the Cervix Kit is a portable Field-programmable gate array (FPGA)-based cervical diagnostic kit that could automatically diagnose the cancerous cell based on the images obtained during sampling test. Besides the cervical diagnostic system, the Neural Mammo system is developed to specifically aid the diagnosis of breast cancer using a fine needle aspiration image.

Listening to Brain Microcircuits for Interfacing With External World—Progress in Wireless Implantable Microelectronic Neuroengineering Devices

PubMed Central

Nurmikko, Arto V.; Donoghue, John P.; Hochberg, Leigh R.; Patterson, William R.; Song, Yoon-Kyu; Bull, Christopher W.; Borton, David A.; Laiwalla, Farah; Park, Sunmee; Ming, Yin; Aceros, Juan

2011-01-01

Acquiring neural signals at high spatial and temporal resolution directly from brain microcircuits and decoding their activity to interpret commands and/or prior planning activity, such as motion of an arm or a leg, is a prime goal of modern neurotechnology. Its practical aims include assistive devices for subjects whose normal neural information pathways are not functioning due to physical damage or disease. On the fundamental side, researchers are striving to decipher the code of multiple neural microcircuits which collectively make up nature’s amazing computing machine, the brain. By implanting biocompatible neural sensor probes directly into the brain, in the form of microelectrode arrays, it is now possible to extract information from interacting populations of neural cells with spatial and temporal resolution at the single cell level. With parallel advances in application of statistical and mathematical techniques tools for deciphering the neural code, extracted populations or correlated neurons, significant understanding has been achieved of those brain commands that control, e.g., the motion of an arm in a primate (monkey or a human subject). These developments are accelerating the work on neural prosthetics where brain derived signals may be employed to bypass, e.g., an injured spinal cord. One key element in achieving the goals for practical and versatile neural prostheses is the development of fully implantable wireless microelectronic “brain-interfaces” within the body, a point of special emphasis of this paper. PMID:21654935

Left-right asymmetry of the Maxwell spot centroids in adults without and with dyslexia.

PubMed

Le Floch, Albert; Ropars, Guy

2017-10-25

In human vision, the brain has to select one view of the world from our two eyes. However, the existence of a clear anatomical asymmetry providing an initial imbalance for normal neural development is still not understood. Using a so-called foveascope, we found that for a cohort of 30 normal adults, the two blue cone-free areas at the centre of the foveas are asymmetrical. The noise-stimulated afterimage dominant eye introduced here corresponds to the circular blue cone-free area, while the non-dominant eye corresponds to the diffuse and irregular elliptical outline. By contrast, we found that this asymmetry is absent or frustrated in a similar cohort of 30 adults with normal ocular status, but with dyslexia, i.e. with visual and phonological deficits. In this case, our results show that the two Maxwell centroid outlines are both circular but lead to an undetermined afterimage dominance with a coexistence of primary and mirror images. The interplay between the lack of asymmetry and the development in the neural maturation of the brain pathways suggests new implications in both fundamental and biomedical sciences. © 2017 The Author(s).

Classification of mass and normal breast tissue: A convolution neural network classifier with spatial domain and texture images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahiner, B.; Chan, H.P.; Petrick, N.

1996-10-01

The authors investigated the classification of regions of interest (ROI`s) on mammograms as either mass or normal tissue using a convolution neural network (CNN). A CNN is a back-propagation neural network with two-dimensional (2-D) weight kernels that operate on images. A generalized, fast and stable implementation of the CNN was developed. The input images to the CNN were obtained form the ROI`s using two techniques. The first technique employed averaging and subsampling. The second technique employed texture feature extraction methods applied to small subregions inside the ROI. Features computed over different subregions were arranged as texture images, which were subsequentlymore » used as CNN inputs. The effects of CNN architecture and texture feature parameters on classification accuracy were studied. Receiver operating characteristic (ROC) methodology was used to evaluate the classification accuracy. A data set consisting of 168 ROI`s containing biopsy-proven masses and 504 ROI`s containing normal breast tissue was extracted from 168 mammograms by radiologists experienced in mammography. This data set was used for training and testing the CNN. With the best combination of CNN architecture and texture feature parameters, the area under the test ROC curve reached 0.87, which corresponded to a true-positive fraction of 90% at a false positive fraction of 31%. The results demonstrate the feasibility of using a CNN for classification of masses and normal tissue on mammograms.« less

Effects of GABA, Neural Regulation, and Intrinsic Cardiac Factors on Heart Rate Variability in Zebrafish Larvae.

PubMed

Vargas, Rafael Antonio

2017-04-01

Heart rate (HR) is a periodic activity that is variable over time due to intrinsic cardiac factors and extrinsic neural control, largely by the autonomic nervous system. Heart rate variability (HRV) is analyzed by measuring consecutive beat-to-beat intervals. This variability can contain information about the factors regulating cardiac activity under normal and pathological conditions, but the information obtained from such analyses is not yet fully understood. In this article, HRV in zebrafish larvae was evaluated under normal conditions and under the effect of substances that modify intrinsic cardiac activity and cardiac activity modulated by the nervous system. We found that the factors affecting intrinsic activity have negative chronotropic and arrhythmogenic effects at this stage of development, whereas neural modulatory factors have a lesser impact. The results suggest that cardiac activity largely depends on the intrinsic properties of the heart tissue in the early stages of development and, to a lesser extent, in the maturing nervous system. We also report, for the first time, the influence of the neurotransmitter gamma amino butyric acid on HRV. The results demonstrate the larval zebrafish model as a useful tool in the study of intrinsic cardiac activity and its role in heart diseases.

What’s bad in cancer is good in the embryo: Importance of EMT in neural crest development

PubMed Central

Kerosuo, Laura; Bronner-Fraser, Marianne

2012-01-01

Although the epithelial to mesenchymal transition (EMT) is famous for its role in cancer metastasis, it also is a normal developmental event in which epithelial cells are converted into migratory mesenchymal cells. A prime example of EMT during development occurs when neural crest (NC) cells emigrate from the neural tube thus providing an excellent model to study the principles of EMT in a nonmalignant environment. NC cells start life as neuroepithelial cells intermixed with precursors of the central nervous system. After EMT, they delaminate and begin migrating, often to distant sites in the embryo. While proliferating and maintaining multipotency and cell survival the transitioning neural crest cells lose apicobasal polarity and the basement membrane is broken down. This review discusses how these events are coordinated and regulated, by series of events involving signaling factors, gene regulatory interactions, as well as epigenetic and post-transcriptional modifications. Even though the series of events involved in NC EMT are well known, the sequence in which these steps take place remains a subject of debate, raising the intriguing possibility that, rather than being a single event, neural crest EMT may involve multiple parallel mechanisms. PMID:22430756

Statistical Mechanical Analysis of Online Learning with Weight Normalization in Single Layer Perceptron

NASA Astrophysics Data System (ADS)

Yoshida, Yuki; Karakida, Ryo; Okada, Masato; Amari, Shun-ichi

2017-04-01

Weight normalization, a newly proposed optimization method for neural networks by Salimans and Kingma (2016), decomposes the weight vector of a neural network into a radial length and a direction vector, and the decomposed parameters follow their steepest descent update. They reported that learning with the weight normalization achieves better converging speed in several tasks including image recognition and reinforcement learning than learning with the conventional parameterization. However, it remains theoretically uncovered how the weight normalization improves the converging speed. In this study, we applied a statistical mechanical technique to analyze on-line learning in single layer linear and nonlinear perceptrons with weight normalization. By deriving order parameters of the learning dynamics, we confirmed quantitatively that weight normalization realizes fast converging speed by automatically tuning the effective learning rate, regardless of the nonlinearity of the neural network. This property is realized when the initial value of the radial length is near the global minimum; therefore, our theory suggests that it is important to choose the initial value of the radial length appropriately when using weight normalization.

Protein content and methyl donors in maternal diet interact to influence the proliferation rate and cell fate of neural stem cells in rat hippocampus.

PubMed

Amarger, Valérie; Lecouillard, Angèle; Ancellet, Laure; Grit, Isabelle; Castellano, Blandine; Hulin, Philippe; Parnet, Patricia

2014-10-14

Maternal diet during pregnancy and early postnatal life influences the setting up of normal physiological functions in the offspring. Epigenetic mechanisms regulate cell differentiation during embryonic development and may mediate gene/environment interactions. We showed here that high methyl donors associated with normal protein content in maternal diet increased the in vitro proliferation rate of neural stem/progenitor cells isolated from rat E19 fetuses. Gene expression on whole hippocampi at weaning confirmed this effect as evidenced by the higher expression of the Nestin and Igf2 genes, suggesting a higher amount of undifferentiated precursor cells. Additionally, protein restriction reduced the expression of the insulin receptor gene, which is essential to the action of IGFII. Inhibition of DNA methylation in neural stem/progenitor cells in vitro increased the expression of the astrocyte-specific Gfap gene and decreased the expression of the neuron-specific Dcx gene, suggesting an impact on cell differentiation. Our data suggest a complex interaction between methyl donors and protein content in maternal diet that influence the expression of major growth factors and their receptors and therefore impact the proliferation and differentiation capacities of neural stem cells, either through external hormone signals or internal genomic regulation.

Graded levels of FGF protein span the midbrain and can instruct graded induction and repression of neural mapping labels

PubMed Central

Chen, Yao; Mohammadi, Moosa; Flanagan, John G.

2009-01-01

Summary Graded guidance labels are widely used in neural map formation, but it is not well understood which potential strategy leads to their graded expression. In midbrain tectal map development, FGFs can induce an entire midbrain, but their protein distribution is unclear, nor is it known whether they may act instructively to produce graded gene expression. Using a receptor-alkaline phosphatase fusion probe, we find a long-range posterior>anterior FGF protein gradient spanning the midbrain. Heparan sulfate proteoglycan (HSPG) is required for this gradient. To test whether graded FGF concentrations can instruct graded gene expression, a quantitative tectal explant assay was developed. Engrailed-2 and ephrin-As, normally in posterior>anterior tectal gradients, showed graded upregulation. Moreover, EphAs, normally in anterior>posterior countergradients, showed coordinately graded downregulation. These results provide a mechanism to establish graded mapping labels, and more generally provide a developmental strategy to coordinately induce a structure and pattern its cell properties in gradients. PMID:19555646

The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium

PubMed Central

Grego-Bessa, Joaquim; Bloomekatz, Joshua; Castel, Pau; Omelchenko, Tatiana; Baselga, José; Anderson, Kathryn V

2016-01-01

Epithelial morphogenesis and stability are essential for normal development and organ homeostasis. The mouse neural plate is a cuboidal epithelium that remodels into a columnar pseudostratified epithelium over the course of 24 hr. Here we show that the transition to a columnar epithelium fails in mutant embryos that lack the tumor suppressor PTEN, although proliferation, patterning and apical-basal polarity markers are normal in the mutants. The Pten phenotype is mimicked by constitutive activation of PI3 kinase and is rescued by the removal of PDK1 (PDPK1), but does not depend on the downstream kinases AKT and mTORC1. High resolution imaging shows that PTEN is required for stabilization of planar cell packing in the neural plate and for the formation of stable apical-basal microtubule arrays. The data suggest that appropriate levels of membrane-associated PDPK1 are required for stabilization of apical junctions, which promotes cell elongation, during epithelial morphogenesis. DOI: http://dx.doi.org/10.7554/eLife.12034.001 PMID:26809587

Inactivation of the ATMIN/ATM pathway protects against glioblastoma formation

PubMed Central

Blake, Sophia M; Stricker, Stefan H; Halavach, Hanna; Poetsch, Anna R; Cresswell, George; Kelly, Gavin; Kanu, Nnennaya; Marino, Silvia; Luscombe, Nicholas M; Pollard, Steven M; Behrens, Axel

2016-01-01

Glioblastoma multiforme (GBM) is the most aggressive human primary brain cancer. Using a Trp53-deficient mouse model of GBM, we show that genetic inactivation of the Atm cofactor Atmin, which is dispensable for embryonic and adult neural development, strongly suppresses GBM formation. Mechanistically, expression of several GBM-associated genes, including Pdgfra, was normalized by Atmin deletion in the Trp53-null background. Pharmacological ATM inhibition also reduced Pdgfra expression, and reduced the proliferation of Trp53-deficient primary glioma cells from murine and human tumors, while normal neural stem cells were unaffected. Analysis of GBM datasets showed that PDGFRA expression is also significantly increased in human TP53-mutant compared with TP53-wild-type tumors. Moreover, combined treatment with ATM and PDGFRA inhibitors efficiently killed TP53-mutant primary human GBM cells, but not untransformed neural stem cells. These results reveal a new requirement for ATMIN-dependent ATM signaling in TP53-deficient GBM, indicating a pro-tumorigenic role for ATM in the context of these tumors. DOI: http://dx.doi.org/10.7554/eLife.08711.001 PMID:26984279

A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting

PubMed Central

Lindeman, Geoffrey J.; Dagnino, Lina; Gaubatz, Stefan; Xu, Yuhui; Bronson, Roderick T.; Warren, Henry B.; Livingston, David M.

1998-01-01

Homozygous E2F-5 knockout embryos and mice have been generated. Although embryonic development appeared normal, newborn mice developed nonobstructive hydrocephalus, suggesting excessive cerebrospinal fluid (CSF) production. Although the CSF-producing choroid plexus displayed normal cellular organization, it contained abundant electron-lucent epithelial cells, consistent with excessive CSF secretory activity. Moreover, E2F-5 CNS expression in normal animals was largely confined to the choroid plexus. Cell cycle kinetics were not perturbed in homozygous knockout embryo fibroblasts. Thus, E2F-5 is not essential for cell proliferation. Rather, it affects the secretory behavior of a differentiated neural tissue. PMID:9553039

Evaluation of supervised machine-learning algorithms to distinguish between inflammatory bowel disease and alimentary lymphoma in cats.

PubMed

Awaysheh, Abdullah; Wilcke, Jeffrey; Elvinger, François; Rees, Loren; Fan, Weiguo; Zimmerman, Kurt L

2016-11-01

Inflammatory bowel disease (IBD) and alimentary lymphoma (ALA) are common gastrointestinal diseases in cats. The very similar clinical signs and histopathologic features of these diseases make the distinction between them diagnostically challenging. We tested the use of supervised machine-learning algorithms to differentiate between the 2 diseases using data generated from noninvasive diagnostic tests. Three prediction models were developed using 3 machine-learning algorithms: naive Bayes, decision trees, and artificial neural networks. The models were trained and tested on data from complete blood count (CBC) and serum chemistry (SC) results for the following 3 groups of client-owned cats: normal, inflammatory bowel disease (IBD), or alimentary lymphoma (ALA). Naive Bayes and artificial neural networks achieved higher classification accuracy (sensitivities of 70.8% and 69.2%, respectively) than the decision tree algorithm (63%, p < 0.0001). The areas under the receiver-operating characteristic curve for classifying cases into the 3 categories was 83% by naive Bayes, 79% by decision tree, and 82% by artificial neural networks. Prediction models using machine learning provided a method for distinguishing between ALA-IBD, ALA-normal, and IBD-normal. The naive Bayes and artificial neural networks classifiers used 10 and 4 of the CBC and SC variables, respectively, to outperform the C4.5 decision tree, which used 5 CBC and SC variables in classifying cats into the 3 classes. These models can provide another noninvasive diagnostic tool to assist clinicians with differentiating between IBD and ALA, and between diseased and nondiseased cats. © 2016 The Author(s).

Amphibian fertilization and development in microgravity

NASA Technical Reports Server (NTRS)

Souza, K. A.; Black, S. D.

1985-01-01

An experiment investigating the effects of gravity on embryonic development in amphibians is proposed. The planned procedures for the preparation of the frog eggs for launching in the Space Shuttle, for the injection of the eggs with gonadotropin, for the insertion of the eggs into egg chambers, for the storage of one of the chambers in a microgravity area and the second into a centrifuge, and for the fertilization of the eggs are described. The later organogenesis, swimming behavior, cytoplasmic components, cellular formation, neural plate and archenteron expansion, and allometry and expansion of the organ systems will be examined. Normal morphology for embryos and tadpoles developing at microgravity and the formation of the neural plate opposite the sperm entry point meridian are predicted.

Neural-Net Processed Characteristic Patterns for Measurement of Structural Integrity of Pressure Cycled Components

NASA Technical Reports Server (NTRS)

Decker, A. J.

2001-01-01

A neural-net inspection process has been combined with a bootstrap training procedure and electronic holography to detect changes or damage in a pressure-cycled International Space Station cold plate to be used for cooling instrumentation. The cold plate was excited to vibrate in a normal mode at low amplitude, and the neural net was trained by example to flag small changes in the mode shape. The NDE (nondestructive-evaluation) technique is straightforward but in its infancy; its applications are ad-hoc and uncalibrated. Nevertheless previous research has shown that the neural net can detect displacement changes to better than 1/100 the maximum displacement amplitude. Development efforts that support the NDE technique are mentioned briefly, followed by descriptions of electronic holography and neural-net processing. The bootstrap training procedure and its application to detection of damage in a pressure-cycled cold plate are discussed. Suggestions for calibrating and quantifying the NDE procedure are presented.

A novel method for extraction of neural response from single channel cochlear implant auditory evoked potentials.

PubMed

Sinkiewicz, Daniel; Friesen, Lendra; Ghoraani, Behnaz

2017-02-01

Cortical auditory evoked potentials (CAEP) are used to evaluate cochlear implant (CI) patient auditory pathways, but the CI device produces an electrical artifact, which obscures the relevant information in the neural response. Currently there are multiple methods, which attempt to recover the neural response from the contaminated CAEP, but there is no gold standard, which can quantitatively confirm the effectiveness of these methods. To address this crucial shortcoming, we develop a wavelet-based method to quantify the amount of artifact energy in the neural response. In addition, a novel technique for extracting the neural response from single channel CAEPs is proposed. The new method uses matching pursuit (MP) based feature extraction to represent the contaminated CAEP in a feature space, and support vector machines (SVM) to classify the components as normal hearing (NH) or artifact. The NH components are combined to recover the neural response without artifact energy, as verified using the evaluation tool. Although it needs some further evaluation, this approach is a promising method of electrical artifact removal from CAEPs. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

High-resolution Imaging of Neural Anatomy and Pathology of the Neck.

PubMed

Lee, Jeong Hyun; Cheng, Kai-Lung; Choi, Young Jun; Baek, Jung Hwan

2017-01-01

The neck has intricately connected neural structures, including cervical and brachial plexi, the sympathetic system, lower cranial nerves, and their branches. Except for brachial plexus, there has been little research regarding the normal imaging appearance or corresponding pathologies of neural structures in the neck. The development in imaging techniques with better spatial resolution and signal-to-noise ratio has made it possible to see many tiny nerves to predict complications related to image-guided procedures and to better assess treatment response, especially in the management of oncology patients. The purposes of this review is to present imaging-based anatomy of major nerves in the neck and explain their relevant clinical significance according to representative pathologies of regarded nerves in the neck.

Neural Stability, Sparing, and Behavioral Recovery Following Brain Damage

ERIC Educational Resources Information Center

LeVere, T. E.

1975-01-01

The present article discusses the possibility that behavioral recovery following brain damage is not dependent on the functional reorganization of neural tissue but is rather the result of the continued normal operation of spared neural mechanisms. (Editor)

The role of retinoic acid in the morphogenesis of the neural tube.

PubMed

Wilson, L; Gale, E; Maden, M

2003-10-01

We have examined the role of the signalling molecule, retinoic acid, in the process of neurulation and the subsequent growth and differentiation of the central nervous system using quail embryos that have developed in the absence of retinoic acid. Such retinoic acid-free embryos undergo abnormal neural tube formation in terms of its shape and structure, but the embryos do not display spina bifida or exencephaly. The neural tubes have a wider floor plate, a thicker roof plate and a different dorsoventral shape. Phalloidin staining and electron microscopy revealed alterations in the actin filaments and the junctional complexes of the cell layer lining the lumen. Initially the neural tubes proliferated at the same rate as normal, but later the proliferation rate declined drastically and neuronal differentiation was highly deficient. There were very few motoneurons extending neurites into the periphery, and within the neural tube axon trajectories were chaotic. These results reveal several functions for retinoic acid in the morphogenesis and growth of the neural tube, many of which can be explained by defective notochord signalling, but they do not suggest that this molecule plays a role in neural tube closure.

High Glucose Inhibits Neural Stem Cell Differentiation Through Oxidative Stress and Endoplasmic Reticulum Stress.

PubMed

Chen, Xi; Shen, Wei-Bin; Yang, Penghua; Dong, Daoyin; Sun, Winny; Yang, Peixin

2018-06-01

Maternal diabetes induces neural tube defects by suppressing neurogenesis in the developing neuroepithelium. Our recent study further revealed that high glucose inhibited embryonic stem cell differentiation into neural lineage cells. However, the mechanism whereby high glucose suppresses neural differentiation is unclear. To investigate whether high glucose-induced oxidative stress and endoplasmic reticulum (ER) stress lead to the inhibition of neural differentiation, the effect of high glucose on neural stem cell (the C17.2 cell line) differentiation was examined. Neural stem cells were cultured in normal glucose (5 mM) or high glucose (25 mM) differentiation medium for 3, 5, and 7 days. High glucose suppressed neural stem cell differentiation by significantly decreasing the expression of the neuron marker Tuj1 and the glial cell marker GFAP and the numbers of Tuj1 + and GFAP + cells. The antioxidant enzyme superoxide dismutase mimetic Tempol reversed high glucose-decreased Tuj1 and GFAP expression and restored the numbers of neurons and glial cells differentiated from neural stem cells. Hydrogen peroxide treatment imitated the inhibitory effect of high glucose on neural stem cell differentiation. Both high glucose and hydrogen peroxide triggered ER stress, whereas Tempol blocked high glucose-induced ER stress. The ER stress inhibitor, 4-phenylbutyrate, abolished the inhibition of high glucose or hydrogen peroxide on neural stem cell differentiation. Thus, oxidative stress and its resultant ER stress mediate the inhibitory effect of high glucose on neural stem cell differentiation.

Contrast normalization contributes to a biologically-plausible model of receptive-field development in primary visual cortex (V1)

PubMed Central

Willmore, Ben D.B.; Bulstrode, Harry; Tolhurst, David J.

2012-01-01

Neuronal populations in the primary visual cortex (V1) of mammals exhibit contrast normalization. Neurons that respond strongly to simple visual stimuli – such as sinusoidal gratings – respond less well to the same stimuli when they are presented as part of a more complex stimulus which also excites other, neighboring neurons. This phenomenon is generally attributed to generalized patterns of inhibitory connections between nearby V1 neurons. The Bienenstock, Cooper and Munro (BCM) rule is a neural network learning rule that, when trained on natural images, produces model neurons which, individually, have many tuning properties in common with real V1 neurons. However, when viewed as a population, a BCM network is very different from V1 – each member of the BCM population tends to respond to the same dominant features of visual input, producing an incomplete, highly redundant code for visual information. Here, we demonstrate that, by adding contrast normalization into the BCM rule, we arrive at a neurally-plausible Hebbian learning rule that can learn an efficient sparse, overcomplete representation that is a better model for stimulus selectivity in V1. This suggests that one role of contrast normalization in V1 is to guide the neonatal development of receptive fields, so that neurons respond to different features of visual input. PMID:22230381

A Failure of Left Temporal Cortex to Specialize for Language Is an Early Emerging and Fundamental Property of Autism

ERIC Educational Resources Information Center

Eyler, Lisa T.; Pierce, Karen; Courchesne, Eric

2012-01-01

Failure to develop normal language comprehension is an early warning sign of autism, but the neural mechanisms underlying this signature deficit are unknown. This is because of an almost complete absence of functional studies of the autistic brain during early development. Using functional magnetic resonance imaging, we previously observed a trend…

Apoptosis regulates notochord development in Xenopus.

PubMed

Malikova, Marina A; Van Stry, Melanie; Symes, Karen

2007-11-15

The notochord is the defining characteristic of the chordate embryo and plays critical roles as a signaling center and as the primitive skeleton. In this study we show that early notochord development in Xenopus embryos is regulated by apoptosis. We find apoptotic cells in the notochord beginning at the neural groove stage and increasing in number as the embryo develops. These dying cells are distributed in an anterior to posterior pattern that is correlated with notochord extension through vacuolization. In axial mesoderm explants, inhibition of this apoptosis causes the length of the notochord to approximately double compared to controls. In embryos, however, inhibition of apoptosis decreases the length of the notochord and it is severely kinked. This kinking also spreads from the anterior with developmental stage such that, by the tadpole stage, the notochord lacks any recognizable structure, although notochord markers are expressed in a normal temporal pattern. Extension of the somites and neural plate mirrors that of the notochord in these embryos, and the somites are severely disorganized. These data indicate that apoptosis is required for normal notochord development during the formation of the anterior-posterior axis, and its role in this process is discussed.

A differential neural response to threatening and non-threatening negative facial expressions in paranoid and non-paranoid schizophrenics.

PubMed

Phillips, M L; Williams, L; Senior, C; Bullmore, E T; Brammer, M J; Andrew, C; Williams, S C; David, A S

1999-11-08

Several studies have demonstrated impaired facial expression recognition in schizophrenia. Few have examined the neural basis for this; none have compared the neural correlates of facial expression perception in different schizophrenic patient subgroups. We compared neural responses to facial expressions in 10 right-handed schizophrenic patients (five paranoid and five non-paranoid) and five normal volunteers using functional Magnetic Resonance Imaging (fMRI). In three 5-min experiments, subjects viewed alternating 30-s blocks of black-and-white facial expressions of either fear, anger or disgust contrasted with expressions of mild happiness. After scanning, subjects categorised each expression. All patients were less accurate in identifying expressions, and showed less activation to these stimuli than normals. Non-paranoids performed poorly in the identification task and failed to activate neural regions that are normally linked with perception of these stimuli. They categorised disgust as either anger or fear more frequently than paranoids, and demonstrated in response to disgust expressions activation in the amygdala, a region associated with perception of fearful faces. Paranoids were more accurate in recognising expressions, and demonstrated greater activation than non-paranoids to most stimuli. We provide the first evidence for a distinction between two schizophrenic patient subgroups on the basis of recognition of and neural response to different negative facial expressions.

Neurophysiological aspects of brainstem processing of speech stimuli in audiometric-normal geriatric population.

PubMed

Ansari, M S; Rangasayee, R; Ansari, M A H

2017-03-01

Poor auditory speech perception in geriatrics is attributable to neural de-synchronisation due to structural and degenerative changes of ageing auditory pathways. The speech-evoked auditory brainstem response may be useful for detecting alterations that cause loss of speech discrimination. Therefore, this study aimed to compare the speech-evoked auditory brainstem response in adult and geriatric populations with normal hearing. The auditory brainstem responses to click sounds and to a 40 ms speech sound (the Hindi phoneme |da|) were compared in 25 young adults and 25 geriatric people with normal hearing. The latencies and amplitudes of transient peaks representing neural responses to the onset, offset and sustained portions of the speech stimulus in quiet and noisy conditions were recorded. The older group had significantly smaller amplitudes and longer latencies for the onset and offset responses to |da| in noisy conditions. Stimulus-to-response times were longer and the spectral amplitude of the sustained portion of the stimulus was reduced. The overall stimulus level caused significant shifts in latency across the entire speech-evoked auditory brainstem response in the older group. The reduction in neural speech processing in older adults suggests diminished subcortical responsiveness to acoustically dynamic spectral cues. However, further investigations are needed to encode temporal cues at the brainstem level and determine their relationship to speech perception for developing a routine tool for clinical decision-making.

Listening to Brain Microcircuits for Interfacing With External World-Progress in Wireless Implantable Microelectronic Neuroengineering Devices: Experimental systems are described for electrical recording in the brain using multiple microelectrodes and short range implantable or wearable broadcasting units.

PubMed

Nurmikko, Arto V; Donoghue, John P; Hochberg, Leigh R; Patterson, William R; Song, Yoon-Kyu; Bull, Christopher W; Borton, David A; Laiwalla, Farah; Park, Sunmee; Ming, Yin; Aceros, Juan

2010-01-01

Acquiring neural signals at high spatial and temporal resolution directly from brain microcircuits and decoding their activity to interpret commands and/or prior planning activity, such as motion of an arm or a leg, is a prime goal of modern neurotechnology. Its practical aims include assistive devices for subjects whose normal neural information pathways are not functioning due to physical damage or disease. On the fundamental side, researchers are striving to decipher the code of multiple neural microcircuits which collectively make up nature's amazing computing machine, the brain. By implanting biocompatible neural sensor probes directly into the brain, in the form of microelectrode arrays, it is now possible to extract information from interacting populations of neural cells with spatial and temporal resolution at the single cell level. With parallel advances in application of statistical and mathematical techniques tools for deciphering the neural code, extracted populations or correlated neurons, significant understanding has been achieved of those brain commands that control, e.g., the motion of an arm in a primate (monkey or a human subject). These developments are accelerating the work on neural prosthetics where brain derived signals may be employed to bypass, e.g., an injured spinal cord. One key element in achieving the goals for practical and versatile neural prostheses is the development of fully implantable wireless microelectronic "brain-interfaces" within the body, a point of special emphasis of this paper.

Hmx1 is required for the normal development of somatosensory neurons in the geniculate ganglion

PubMed Central

Quina, Lely A.; Tempest, Lynne; Hsu, Yun-Wei A.; Cox, Timothy C.; Turner, Eric E.

2012-01-01

Hmx1 is a variant homeodomain transcription factor expressed in the developing sensory nervous system, retina, and craniofacial mesenchyme. Recently, mutations at the Hmx1 locus have been linked to craniofacial defects in humans, rats, and mice, but its role in nervous system development is largely unknown. Here we show that Hmx1 is expressed in a subset of sensory neurons in the cranial and dorsal root ganglia which does not correspond to any specific sensory modality. Sensory neurons in the dorsal root and trigeminal ganglia of Hmx1dm/dm mouse embryos have no detectable Hmx1 protein, yet they undergo neurogenesis and express sensory subtype markers normally, demonstrating that Hmx1 is not globally required for the specification of sensory neurons from neural crest precursors. Loss of Hmx1 expression has no obvious effect on the early development of the trigeminal (V), superior (IX/X), or dorsal root ganglia neurons in which it is expressed, but results in marked defects in the geniculate (VII) ganglion. Hmx1dm/dm mouse embryos possess only a vestigial posterior auricular nerve, and general somatosensory neurons in the geniculate ganglion are greatly reduced by mid-gestation. Although Hmx1 is expressed in geniculate neurons prior to cell cycle exit, it does not appear to be required for neurogenesis, and the loss of geniculate neurons is likely to be the result of increased cell death. Fate mapping of neural crest-derived tissues indicates that Hmx1-expressing somatosensory neurons at different axial levels may be derived from either the neural crest or the neurogenic placodes. PMID:22586713

Detection of flow limitation in obstructive sleep apnea with an artificial neural network.

PubMed

Norman, Robert G; Rapoport, David M; Ayappa, Indu

2007-09-01

During sleep, the development of a plateau on the inspiratory airflow/time contour provides a non-invasive indicator of airway collapsibility. Humans recognize this abnormal contour easily, and this study replicates this with an artificial neural network (ANN) using a normalized shape. Five 10 min segments were selected from each of 18 sleep records (respiratory airflow measured with a nasal cannula) with varying degrees of sleep disordered breathing. Each breath was visually scored for shape, and breaths split randomly into a training and test set. Equally spaced, peak amplitude normalized flow values (representing breath shape) formed the only input to a back propagation ANN. Following training, breath-by-breath agreement of the ANN with the manual classification was tabulated for the training and test sets separately. Agreement of the ANN was 89% in the training set and 70.6% in the test set. When the categories of 'probably normal' and 'normal', and 'probably flow limited' and 'flow limited' were combined, the agreement increased to 92.7% and 89.4% respectively, similar to the intra- and inter-rater agreements obtained by a visual classification of these breaths. On a naive dataset, the agreement of the ANN to visual classification was 57.7% overall and 82.4% when the categories were collapsed. A neural network based only on the shape of inspiratory airflow succeeded in classifying breaths as to the presence/absence of flow limitation. This approach could be used to provide a standardized, reproducible and automated means of detecting elevated upper airway resistance.

Notch signaling and ageing.

PubMed

Polychronidou, Eleftheria; Vlachakis, Dimitrios; Vlamos, Panayiotis; Baumann, Marc; Kossida, Sophia

2015-01-01

Notch signaling is a master controller of the neural stem cell and neural development maintaining a significant role in the normal brain function. Notch genes are involved in embryogenesis, nervous system, and cardiovascular and endocrine function. On the other side, there are studies representing the involvement of Notch mutations in sporadic Alzheimer disease, other neurodegenerative diseases such as Down syndrome, Pick's and Prion's disease, and CADASIL. This manuscript attempts to present a holistic view of the positive or negative contribution of Notch signaling in the adult brain, and at the same time to present and promote the promising research fields of study.

Identification of Abnormal System Noise Temperature Patterns in Deep Space Network Antennas Using Neural Network Trained Fuzzy Logic

NASA Technical Reports Server (NTRS)

Lu, Thomas; Pham, Timothy; Liao, Jason

2011-01-01

This paper presents the development of a fuzzy logic function trained by an artificial neural network to classify the system noise temperature (SNT) of antennas in the NASA Deep Space Network (DSN). The SNT data were classified into normal, marginal, and abnormal classes. The irregular SNT pattern was further correlated with link margin and weather data. A reasonably good correlation is detected among high SNT, low link margin and the effect of bad weather; however we also saw some unexpected non-correlations which merit further study in the future.

Maintenance of Mouse Gustatory Terminal Field Organization Is Disrupted following Selective Removal of Peripheral Sodium Salt Taste Activity at Adulthood

PubMed Central

Sun, Chengsan

2017-01-01

Neural activity plays a critical role in the development of central circuits in sensory systems. However, the maintenance of these circuits at adulthood is usually not dependent on sensory-elicited neural activity. Recent work in the mouse gustatory system showed that selectively deleting the primary transduction channel for sodium taste, the epithelial sodium channel (ENaC), throughout development dramatically impacted the organization of the central terminal fields of three nerves that carry taste information to the nucleus of the solitary tract. More specifically, deleting ENaCs during development prevented the normal maturation of the fields. The present study was designed to extend these findings by testing the hypothesis that the loss of sodium taste activity impacts the maintenance of the normal adult terminal field organization in male and female mice. To do this, we used an inducible Cre-dependent genetic recombination strategy to delete ENaC function after terminal field maturation occurred. We found that removal of sodium taste neural activity at adulthood resulted in significant reorganization of mature gustatory afferent terminal fields in the nucleus of the solitary tract. Specifically, the chorda tympani and greater superficial petrosal nerve terminal fields were 1.4× and 1.6× larger than age-matched controls, respectively. By contrast, the glossopharyngeal nerve, which is not highly sensitive to sodium taste stimulation, did not undergo terminal field reorganization. These surprising results suggest that gustatory nerve terminal fields remain plastic well into adulthood, which likely impacts central coding of taste information and taste-related behaviors with altered taste experience. SIGNIFICANCE STATEMENT Neural activity plays a major role in the development of sensory circuits in the mammalian brain. However, the importance of sensory-driven activity in maintaining these circuits at adulthood, especially in subcortical structures, appears to be much less. Here, we tested whether the loss of sodium taste activity in adult mice impacts the maintenance of how taste nerves project to the first central relay. We found that specific loss of sodium-elicited taste activity at adulthood produced dramatic and selective reorganization of terminal fields in the brainstem. This demonstrates, for the first time, that taste-elicited activity is necessary for the normal maintenance of central gustatory circuits at adulthood and highlights a level of plasticity not seen in other sensory system subcortical circuits. PMID:28676575

Neural coordination can be enhanced by occasional interruption of normal firing patterns: a self-optimizing spiking neural network model.

PubMed

Woodward, Alexander; Froese, Tom; Ikegami, Takashi

2015-02-01

The state space of a conventional Hopfield network typically exhibits many different attractors of which only a small subset satisfies constraints between neurons in a globally optimal fashion. It has recently been demonstrated that combining Hebbian learning with occasional alterations of normal neural states avoids this problem by means of self-organized enlargement of the best basins of attraction. However, so far it is not clear to what extent this process of self-optimization is also operative in real brains. Here we demonstrate that it can be transferred to more biologically plausible neural networks by implementing a self-optimizing spiking neural network model. In addition, by using this spiking neural network to emulate a Hopfield network with Hebbian learning, we attempt to make a connection between rate-based and temporal coding based neural systems. Although further work is required to make this model more realistic, it already suggests that the efficacy of the self-optimizing process is independent from the simplifying assumptions of a conventional Hopfield network. We also discuss natural and cultural processes that could be responsible for occasional alteration of neural firing patterns in actual brains. Copyright © 2014 Elsevier Ltd. All rights reserved.

Zika virus has oncolytic activity against glioblastoma stem cells

PubMed Central

Gorman, Matthew J.; McKenzie, Lisa D.; Hubert, Christopher G.; Prager, Briana C.; Fernandez, Estefania; Richner, Justin M.; Zhang, Rong; Shan, Chao; Tycksen, Eric; Shi, Pei-Yong

2017-01-01

Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells. ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a mouse-adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs; thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients. PMID:28874392

Study of Aided Diagnosis of Hepatic Carcinoma Based on Artificial Neural Network Combined with Tumor Marker Group

NASA Astrophysics Data System (ADS)

Tan, Shanjuan; Feng, Feifei; Wu, Yongjun; Wu, Yiming

To develop a computer-aided diagnostic scheme by using an artificial neural network (ANN) combined with tumor markers for diagnosis of hepatic carcinoma (HCC) as a clinical assistant method. 140 serum samples (50 malignant, 40 benign and 50 normal) were analyzed for α-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), sialic acid (SA) and calcium (Ca). The five tumor marker values were then used as ANN inputs data. The result of ANN was compared with that of discriminant analysis by receiver operating characteristic (ROC) curve (AUC) analysis. The diagnostic accuracy of ANN and discriminant analysis among all samples of the test group was 95.5% and 79.3%, respectively. Analysis of multiple tumor markers based on ANN may be a better choice than the traditional statistical methods for differentiating HCC from benign or normal.

Prefrontal consolidation supports the attainment of fear memory accuracy

PubMed Central

Vieira, Philip A.; Lovelace, Jonathan W.; Corches, Alex; Rashid, Asim J.; Josselyn, Sheena A.

2014-01-01

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive. PMID:25031365

Artificial neural network for normal, hypertensive, and preeclamptic pregnancy classification using maternal heart rate variability indexes.

PubMed

Tejera, Eduardo; Jose Areias, Maria; Rodrigues, Ana; Ramõa, Ana; Manuel Nieto-Villar, Jose; Rebelo, Irene

2011-09-01

A model construction for classification of women with normal, hypertensive and preeclamptic pregnancy in different gestational ages using maternal heart rate variability (HRV) indexes. In the present work, we applied the artificial neural network for the classification problem, using the signal composed by the time intervals between consecutive RR peaks (RR) (n = 568) obtained from ECG records. Beside the HRV indexes, we also considered other factors like maternal history and blood pressure measurements. The obtained result reveals sensitivity for preeclampsia around 80% that increases for hypertensive and normal pregnancy groups. On the other hand, specificity is around 85-90%. These results indicate that the combination of HRV indexes with artificial neural networks (ANN) could be helpful for pregnancy study and characterization.

[Osteological development of the vertebral column and caudal complex of Lujanus guttatus (Perciformes: Lutjanidae) larvae under rearing conditions].

PubMed

Rodríguez-Ibarra, Luz Estela; Abdo-de la Parra, María Isabel; Aguilar-Zárate, Gabriela; Valasco-Blanco, Gabriela; Ibarra-Castro, Leonardo

2015-03-01

The spotted rose snapper (Lutjanus guttatus) is an important commercial species in Mexico with good culture potential. The osteological study at early stages in this species is an important tool to confirm normal bone structure and for the detection of malformations that may occur during early development. This study was carried out in order to evaluate and describe the normal osteological development of the vertebral column and caudal complex of this species grown under controlled conditions. For this, a total of 540 larvae of L. guttatus, between 2.1 and 17.5 mm of total length (TL), were cultured during 36 days; culture conditions were 28 degrees C, 5.74 mg/L oxygen and 32.2 ups salinity with standard feeding rates. To detect growth changes, a sample of 15 organisms was daily taken from day one until day 36 of post-hatch (DPH). Samples were processed following standard techniques of clearing, and cartilage (alcian blue) and bone staining (alizarin red). Results showed that the vertebral column is composed of ten vertebrae in the abdominal region, and 14 vertebrae including the urostyle in the caudal region. The development of the axial skeleton starts with the neural arches and haemal arches at 3.8 mm TL. Caudal elements such as the hypurals and parahypural began to develop at 4.1 mm TL. Pre-flexion and flexion of the notochord and the formation of all hypurals were observed between 5.3 and 5.8 mm TL. Ossification of the vertebrae in the abdominal region and in some neural arches initiated at 9.5mm TL. In the caudal region, all the neural and haemal arches ossified at 10.2 mm TL. All the abdominal vertebrae and their respective neural arches and parapophyses ossified at 11.2 mm TL, while the elements of the caudal complex that ossified were the hypurals, parahypurals and modified haemal spines. All caudal fm rays, 12 neural spines and 3 haemal arches were ossified by 15.5 mm. The complete ossification process of this specie under laboratory culture conditions was observed when larvae reached 17.3 mm TL on 36 DPH. Detailed analysis of the osteological structures will allow a reference description to evaluate and detect malformations that may occur during the larval culture of the spotted rose snapper.

Arrested development: early prefrontal lesions impair the maturation of moral judgement.

PubMed

Taber-Thomas, Bradley C; Asp, Erik W; Koenigs, Michael; Sutterer, Matthew; Anderson, Steven W; Tranel, Daniel

2014-04-01

Learning to make moral judgements based on considerations beyond self-interest is a fundamental aspect of moral development. A deficit in such learning is associated with poor socialization and criminal behaviour. The neural systems required for the acquisition and maturation of moral competency are not well understood. Here we show in a unique sample of neurological patients that focal lesions involving ventromedial prefrontal cortex, acquired during development, result in an abnormally egocentric pattern of moral judgement. In response to simple hypothetical moral scenarios, the patients were more likely than comparison participants to endorse self-interested actions that involved breaking moral rules or physically harming others in order to benefit themselves. This pattern (which we also found in subjects with psychopathy) differs from that of patients with adult-onset ventromedial prefrontal cortex lesions--the latter group showed normal rejection of egocentric rule violations. This novel contrast of patients with ventromedial prefrontal cortex lesions acquired during development versus during adulthood yields new evidence suggesting that the ventromedial prefrontal cortex is a critical neural substrate for the acquisition and maturation of moral competency that goes beyond self-interest to consider the welfare of others. Disruption to this affective neural system early in life interrupts moral development.

Collagen 18 and agrin are secreted by neural crest cells to remodel their microenvironment and regulate their migration during enteric nervous system development.

PubMed

Nagy, Nandor; Barad, Csilla; Hotta, Ryo; Bhave, Sukhada; Arciero, Emily; Dora, David; Goldstein, Allan M

2018-05-08

The enteric nervous system (ENS) arises from neural crest cells that migrate, proliferate, and differentiate into enteric neurons and glia within the intestinal wall. Many extracellular matrix (ECM) components are present in the embryonic gut, but their role in regulating ENS development is largely unknown. Here, we identify heparan sulfate proteoglycan proteins, including collagen XVIII (Col18) and agrin, as important regulators of enteric neural crest-derived cell (ENCDC) development. In developing avian hindgut, Col18 is expressed at the ENCDC wavefront, while agrin expression occurs later. Both proteins are normally present around enteric ganglia, but are absent in aganglionic gut. Using chick-mouse intestinal chimeras and enteric neurospheres, we show that vagal- and sacral-derived ENCDCs from both species secrete Col18 and agrin. Whereas glia express Col18 and agrin, enteric neurons only express the latter. Functional studies demonstrate that Col18 is permissive whereas agrin is strongly inhibitory to ENCDC migration, consistent with the timing of their expression during ENS development. We conclude that ENCDCs govern their own migration by actively remodeling their microenvironment through secretion of ECM proteins. © 2018. Published by The Company of Biologists Ltd.

Automated EEG-based screening of depression using deep convolutional neural network.

PubMed

Acharya, U Rajendra; Oh, Shu Lih; Hagiwara, Yuki; Tan, Jen Hong; Adeli, Hojjat; Subha, D P

2018-07-01

In recent years, advanced neurocomputing and machine learning techniques have been used for Electroencephalogram (EEG)-based diagnosis of various neurological disorders. In this paper, a novel computer model is presented for EEG-based screening of depression using a deep neural network machine learning approach, known as Convolutional Neural Network (CNN). The proposed technique does not require a semi-manually-selected set of features to be fed into a classifier for classification. It learns automatically and adaptively from the input EEG signals to differentiate EEGs obtained from depressive and normal subjects. The model was tested using EEGs obtained from 15 normal and 15 depressed patients. The algorithm attained accuracies of 93.5% and 96.0% using EEG signals from the left and right hemisphere, respectively. It was discovered in this research that the EEG signals from the right hemisphere are more distinctive in depression than those from the left hemisphere. This discovery is consistent with recent research and revelation that the depression is associated with a hyperactive right hemisphere. An exciting extension of this research would be diagnosis of different stages and severity of depression and development of a Depression Severity Index (DSI). Copyright © 2018 Elsevier B.V. All rights reserved.

The Human Central Pattern Generator for Locomotion.

PubMed

Minassian, Karen; Hofstoetter, Ursula S; Dzeladini, Florin; Guertin, Pierre A; Ijspeert, Auke

2017-03-01

The ability of dedicated spinal circuits, referred to as central pattern generators (CPGs), to produce the basic rhythm and neural activation patterns underlying locomotion can be demonstrated under specific experimental conditions in reduced animal preparations. The existence of CPGs in humans is a matter of debate. Equally elusive is the contribution of CPGs to normal bipedal locomotion. To address these points, we focus on human studies that utilized spinal cord stimulation or pharmacological neuromodulation to generate rhythmic activity in individuals with spinal cord injury, and on neuromechanical modeling of human locomotion. In the absence of volitional motor control and step-specific sensory feedback, the human lumbar spinal cord can produce rhythmic muscle activation patterns that closely resemble CPG-induced neural activity of the isolated animal spinal cord. In this sense, CPGs in humans can be defined by the activity they produce. During normal locomotion, CPGs could contribute to the activation patterns during specific phases of the step cycle and simplify supraspinal control of step cycle frequency as a feedforward component to achieve a targeted speed. Determining how the human CPGs operate will be essential to advance the theory of neural control of locomotion and develop new locomotor neurorehabilitation paradigms.

Automated radial basis function neural network based image classification system for diabetic retinopathy detection in retinal images

NASA Astrophysics Data System (ADS)

Anitha, J.; Vijila, C. Kezi Selva; Hemanth, D. Jude

2010-02-01

Diabetic retinopathy (DR) is a chronic eye disease for which early detection is highly essential to avoid any fatal results. Image processing of retinal images emerge as a feasible tool for this early diagnosis. Digital image processing techniques involve image classification which is a significant technique to detect the abnormality in the eye. Various automated classification systems have been developed in the recent years but most of them lack high classification accuracy. Artificial neural networks are the widely preferred artificial intelligence technique since it yields superior results in terms of classification accuracy. In this work, Radial Basis function (RBF) neural network based bi-level classification system is proposed to differentiate abnormal DR Images and normal retinal images. The results are analyzed in terms of classification accuracy, sensitivity and specificity. A comparative analysis is performed with the results of the probabilistic classifier namely Bayesian classifier to show the superior nature of neural classifier. Experimental results show promising results for the neural classifier in terms of the performance measures.

Real-time camera-based face detection using a modified LAMSTAR neural network system

NASA Astrophysics Data System (ADS)

Girado, Javier I.; Sandin, Daniel J.; DeFanti, Thomas A.; Wolf, Laura K.

2003-03-01

This paper describes a cost-effective, real-time (640x480 at 30Hz) upright frontal face detector as part of an ongoing project to develop a video-based, tetherless 3D head position and orientation tracking system. The work is specifically targeted for auto-stereoscopic displays and projection-based virtual reality systems. The proposed face detector is based on a modified LAMSTAR neural network system. At the input stage, after achieving image normalization and equalization, a sub-window analyzes facial features using a neural network. The sub-window is segmented, and each part is fed to a neural network layer consisting of a Kohonen Self-Organizing Map (SOM). The output of the SOM neural networks are interconnected and related by correlation-links, and can hence determine the presence of a face with enough redundancy to provide a high detection rate. To avoid tracking multiple faces simultaneously, the system is initially trained to track only the face centered in a box superimposed on the display. The system is also rotationally and size invariant to a certain degree.

Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development.

PubMed

Storer, Mekayla A; Gallagher, Denis; Fatt, Michael P; Simonetta, Jaclin V; Kaplan, David R; Miller, Freda D

2018-05-08

Circulating systemic factors can regulate adult neural stem cell (NSC) biology, but the identity of these circulating cues is still being defined. Here, we have focused on the cytokine interleukin-6 (IL-6), since increased circulating levels of IL-6 are associated with neural pathologies such as autism and bipolar disorder. We show that IL-6 promotes proliferation of post-natal murine forebrain NSCs and that, when the IL-6 receptor is inducibly knocked out in post-natal or adult neural precursors, this causes a long-term decrease in forebrain NSCs. Moreover, a transient circulating surge of IL-6 in perinatal or adult mice causes an acute increase in neural precursor proliferation followed by long-term depletion of adult NSC pools. Thus, IL-6 signaling is both necessary and sufficient for adult NSC self-renewal, and acute perturbations in circulating IL-6, as observed in many pathological situations, have long-lasting effects on the size of adult NSC pools. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Cell death in neural precursor cells and neurons before neurite formation prevents the emergence of abnormal neural structures in the Drosophila optic lobe.

PubMed

Hara, Yusuke; Sudo, Tatsuya; Togane, Yu; Akagawa, Hiromi; Tsujimura, Hidenobu

2018-04-01

Programmed cell death is a conserved strategy for neural development both in vertebrates and invertebrates and is recognized at various developmental stages in the brain from neurogenesis to adulthood. To understand the development of the central nervous system, it is essential to reveal not only molecular mechanisms but also the role of neural cell death (Pinto-Teixeira et al., 2016). To understand the role of cell death in neural development, we investigated the effect of inhibition of cell death on optic lobe development. Our data demonstrate that, in the optic lobe of Drosophila, cell death occurs in neural precursor cells and neurons before neurite formation and functions to prevent various developmental abnormalities. When neuronal cell death was inhibited by an effector caspase inhibitor, p35, multiple abnormal neuropil structures arose during optic lobe development-e.g., enlarged or fused neuropils, misrouted neurons and abnormal neurite lumps. Inhibition of cell death also induced morphogenetic defects in the lamina and medulla development-e.g., failures in the separation of the lamina and medulla cortices and the medulla rotation. These defects were reproduced in the mutant of an initiator caspase, dronc. If cell death was a mechanism for removing the abnormal neuropil structures, we would also expect to observe them in mutants defective for corpse clearance. However, they were not observed in these mutants. When dead cell-membranes were visualized with Apoliner, they were observed only in cortices and not in neuropils. These results suggest that the cell death occurs before mature neurite formation. Moreover, we found that inhibition of cell death induced ectopic neuroepithelial cells, neuroblasts and ganglion mother cells in late pupal stages, at sites where the outer and inner proliferation centers were located at earlier developmental stages. Caspase-3 activation was observed in the neuroepithelial cells and neuroblasts in the proliferation centers. These results indicate that cell death is required for elimination of the precursor cells composing the proliferation centers. This study substantiates an essential role of early neural cell death for ensuring normal development of the central nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

White spotting phenotype induced by targeted REST disruption during neural crest specification to a melanocyte cell lineage.

PubMed

Aoki, Hitomi; Hara, Akira; Kunisada, Takahiro

2015-05-01

Neural crest cells (NCCs) emerge from the dorsal region of the neural tube of vertebrate embryos and have the pluripotency to differentiate into both neuronal and non-neuronal lineages including melanocytes. Rest, also known as NRSF (neuro-restrictive silencer factor), is a regulator of neuronal development and function and suggested to be involved in the lineage specification of NCCs. However, further investigations of Rest gene functions in vivo have been hampered by the fact that Rest null mice show early embryonic lethality. To investigate the function of Rest in NCC development, we recently established NCC-specific Rest conditional knockout (CKO) mice and observed their neonatal death. Here, we have established viable heterozygous NCC-specific Rest CKO mice to analyze the function of Rest in an NCC-derived melanocyte cell lineage and found that the white spotting phenotype was associated with the reduction in the number of melanoblasts in the embryonic skin. The Rest deletion induced after the specification to melanocytes did not reduce the number of melanoblasts; therefore, the expression of REST during the early neural crest specification stage was necessary for the normal development of melanoblasts to cover all of the skin. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Neural Evidence of Allophonic Perception in Children at Risk for Dyslexia

ERIC Educational Resources Information Center

Noordenbos, M. W.; Segers, E.; Serniclaes, W.; Mitterer, H.; Verhoeven, L.

2012-01-01

Learning to read is a complex process that develops normally in the majority of children and requires the mapping of graphemes to their corresponding phonemes. Problems with the mapping process nevertheless occur in about 5% of the population and are typically attributed to poor phonological representations, which are--in turn--attributed to…

Gliomagenesis and neural stem cells: Key role of hypoxia and concept of tumor "neo-niche".

PubMed

Diabira, Sylma; Morandi, Xavier

2008-01-01

Gliomas represent the most common primary brain tumors and the most devastating pathology of the central nervous system. Despite progress in conventional treatments, the prognosis remains dismal. Recent studies have suggested that a glioma brain tumor may arise from a "cancer stem cell". To understand this theory we summarize studies of the concepts of neural stem cell, and its specialized microenvironment, namely the niche which can regulate balanced self-renewal, differentiation and stem cell quiescence. We summarize the molecular mechanism known or postulated to be involved in the disregulation of normal stem cells features allowing them to undergo neoplasic transformation. We seek data pointing out the key role of hypoxia in normal homeostasis of stem cells and in the initiation, development and aggressiveness of gliomas. We develop the concept of tumor special microenvironment and we propose the new concept of neo-niche, surrounding the glioma, in which hypoxia could be a key factor to recruit and deregulate different stem cells for gliogenesis process. Substantial advances in treatment would come from obtaining better knowledge of molecular impairs of this disease.

Memory in ASD: Have We Been Barking up the Wrong Tree?

ERIC Educational Resources Information Center

Boucher, Jill; Mayes, Andrew

2012-01-01

In this theoretical note, possible neural causes of episodic memory impairment in individuals with ASD and currently normal intellectual and linguistic function are considered. The neural causes most commonly argued for are hippocampal or prefrontal cortex dysfunction, associated with impaired neural connectivity. It is argued here that a…

Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders.

PubMed

Jaiswal, Preeti; Mohanakumar, Kochupurackal P; Rajamma, Usha

2015-08-01

Serotonergic system has long been implicated in the aetiology of autism spectrum disorders (ASD), since platelet hyperserotonemia is consistently observed in a subset of autistic patients, who respond well to selective serotonin reuptake inhibitors. Apart from being a neurotransmitter, serotonin functions as a neurotrophic factor directing brain development and as an immunoregulator modulating immune responses. Serotonin transporter (SERT) regulates serotonin level in lymphoid tissues to ensure its proper functioning in innate and adaptive responses. Immunological molecules such as cytokines in turn regulate the transcription and activity of SERT. Dysregulation of serotonergic system could trigger signalling cascades that affect normal neural-immune interactions culminating in neurodevelopmental and neural connectivity defects precipitating behavioural abnormalities, or the disease phenotypes. Therefore, we suggest that a better understanding of the cross talk between serotonergic genes, immune systems and serotonergic neurotransmission will open wider avenues to develop pharmacological leads for addressing the core ASD behavioural deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

An orthologue of the kit-related gene fms is required for development of neural crest-derived xanthophores and a subpopulation of adult melanocytes in the zebrafish, Danio rerio.

PubMed

Parichy, D M; Ransom, D G; Paw, B; Zon, L I; Johnson, S L

2000-07-01

Developmental mechanisms underlying traits expressed in larval and adult vertebrates remain largely unknown. Pigment patterns of fishes provide an opportunity to identify genes and cell behaviors required for postembryonic morphogenesis and differentiation. In the zebrafish, Danio rerio, pigment patterns reflect the spatial arrangements of three classes of neural crest-derived pigment cells: black melanocytes, yellow xanthophores and silver iridophores. We show that the D. rerio pigment pattern mutant panther ablates xanthophores in embryos and adults and has defects in the development of the adult pattern of melanocyte stripes. We find that panther corresponds to an orthologue of the c-fms gene, which encodes a type III receptor tyrosine kinase and is the closest known homologue of the previously identified pigment pattern gene, kit. In mouse, fms is essential for the development of macrophage and osteoclast lineages and has not been implicated in neural crest or pigment cell development. In contrast, our analyses demonstrate that fms is expressed and required by D. rerio xanthophore precursors and that fms promotes the normal patterning of melanocyte death and migration during adult stripe formation. Finally, we show that fms is required for the appearance of a late developing, kit-independent subpopulation of adult melanocytes. These findings reveal an unexpected role for fms in pigment pattern development and demonstrate that parallel neural crest-derived pigment cell populations depend on the activities of two essentially paralogous genes, kit and fms.

Characterization of axon formation in the embryonic stem cell-derived motoneuron.

PubMed

Pan, Hung-Chuan; Wu, Ya-Ting; Shen, Shih-Cheng; Wang, Chi-Chung; Tsai, Ming-Shiun; Cheng, Fu-Chou; Lin, Shinn-Zong; Chen, Ching-Wen; Liu, Ching-San; Su, Hong-Lin

2011-01-01

The developing neural cell must form a highly organized architecture to properly receive and transmit nerve signals. Neural formation from embryonic stem (ES) cells provides a novel system for studying axonogenesis, which are orchestrated by polarity-regulating molecules. Here the ES-derived motoneurons, identified by HB9 promoter-driven green fluorescent protein (GFP) expression, showed characteristics of motoneuron-specific gene expression. In the majority of motoneurons, one of the bilateral neurites developed into an axon that featured with axonal markers, including Tau1, vesicle acetylcholine transporter, and synaptophysin. Interestingly, one third of the motoneurons developed bi-axonal processes but no multiple axonal GFP cell was found. The neuronal polarity-regulating proteins, including the phosphorylated AKT and ERK, were compartmentalized into both of the bilateral axonal tips. Importantly, this aberrant axon morphology was still present after the engraftment of GFP(+) neurons into the spinal cord, suggesting that even a mature neural environment fails to provide a proper niche to guide normal axon formation. These findings underscore the necessity for evaluating the morphogenesis and functionality of neurons before the clinical trials using ES or somatic stem cells.

Neural Methods for Imagery, GMTI, and Information Fusion

DTIC Science & Technology

2006-03-15

Dynamic Range Contrast Enhanced Length & Power Normalized JV\\ 0.7 11 2500. No0 00 0.6 :a -30 - i 0.5 1 •4e ,3 ta I. a* 20 4B 60 Be° .0 120 140 160 s e...conditioned profile after length and power normalization. 2 Neural-Based Feature Extraction 2.2 Contrast enhancement and adaptive Rather than directly... power of the signal comprised of HRR range profiles synthesized from the is normalized. This ensures that very weak or very strong MSTAR SAR imagery

Neural and receptor cochlear potentials obtained by transtympanic electrocochleography in auditory neuropathy.

PubMed

Santarelli, Rosamaria; Starr, Arnold; Michalewski, Henry J; Arslan, Edoardo

2008-05-01

Transtympanic electrocochleography (ECochG) was recorded bilaterally in children and adults with auditory neuropathy (AN) to evaluate receptor and neural generators. Test stimuli were clicks from 60 to 120dB p.e. SPL. Measures obtained from eight AN subjects were compared to 16 normally hearing children. Receptor cochlear microphonics (CMs) in AN were of normal or enhanced amplitude. Neural compound action potentials (CAPs) and receptor summating potentials (SPs) were identified in five AN ears. ECochG potentials in those ears without CAPs were of negative polarity and of normal or prolonged duration. We used adaptation to rapid stimulus rates to distinguish whether the generators of the negative potentials were of neural or receptor origin. Adaptation in controls resulted in amplitude reduction of CAP twice that of SP without affecting the duration of ECochG potentials. In seven AN ears without CAP and with prolonged negative potential, adaptation was accompanied by reduction of both amplitude and duration of the negative potential to control values consistent with neural generation. In four ears without CAP and with normal duration potentials, adaptation was without effect consistent with receptor generation. In five AN ears with CAP, there was reduction in amplitude of CAP and SP as controls but with a significant decrease in response duration. Three patterns of cochlear potentials were identified in AN: (1) presence of receptor SP without CAP consistent with pre-synaptic disorder of inner hair cells; (2) presence of both SP and CAP consistent with post-synaptic disorder of proximal auditory nerve; (3) presence of prolonged neural potentials without a CAP consistent with post-synaptic disorder of nerve terminals. Cochlear potential measures may identify pre- and post-synaptic disorders of inner hair cells and auditory nerves in AN.

The effects of levetiracetam on neural tube development in the early stage of chick embryos.

PubMed

Guvenc, Yahya; Dalgic, Ali; Billur, Deniz; Karaoglu, Derya; Aydin, Sevim; Daglioglu, Ergun; Ozdol, Cagatay; Nacar, Osman Arikan; Yildirim, Ali Erdem; Belen, Deniz

2013-01-01

This study aimed to investigate the effects of a new generation antiepileptic agent, levetiracetam, on the neural tube development in a chick embryo model that corresponds to the first month of vertebral development in mammals. Forty-five Atabey® breed fertilized chicken eggs with no specific pathogens were randomly divided into 5 groups. All of the eggs were incubated at 37.8±2°C and 60±5 % relative humidity in an incubator. Group A was control group. The other eggs were applied physiological saline and drugs at a volume of 10 μL by the in ovo method at the 28th hour of the incubation period. Group B was given distilled water; Group C, physiological saline; Group D, Levetiracetam (L8668) at a dose equivalent to the treatment dose for humans (10 mg/ kg), and Group E, Levetiracetam (L8668) at a dose of 10 times the treatment dose. The embryos in all of the groups were removed from the shells at the 48th hour and morphologically and histologically evaluated. Of the 45 embryos incubated, neural tubes of 41 were closed and the embryos displayed normal development. Levetiracetam, at a dose equivalent to human treatment dose and 10 times the treatment dose, was shown not to cause neural tube defects in chick embryos.

Astrocyte-Secreted Factors Selectively Alter Neural Stem and Progenitor Cell Proliferation in the Fragile X Mouse

PubMed Central

Sourial, Mary; Doering, Laurie C.

2016-01-01

An increasing body of evidence indicates that astrocytes contribute to the governance and fine tuning of stem and progenitor cell production during brain development. The effect of astrocyte function in cell production in neurodevelopmental disorders is unknown. We used the Neural Colony Forming Cell assay to determine the effect of astrocyte conditioned media (ACM) on the generation of neurospheres originating from either progenitor cells or functional stem cells in the knock out (KO) Fragile X mouse model. ACM from both normal and Fmr1-KO mice generated higher percentages of smaller neurospheres indicative of restricted proliferation of the progenitor cell population in Fmr1-KO brains. Wild type (WT) neurospheres, but not KO neurospheres, showed enhanced responses to ACM from the Fmr1-KO mice. In particular, Fmr1-KO ACM increased the percentage of large neurospheres generated, representative of spheres produced from neural stem cells. We also used 2D DIGE to initiate identification of the astrocyte-secreted proteins with differential expression between Fmr1-KO and WT cortices and hippocampi. The results further support the critical role of astrocytes in governing neural cell production in brain development and point to significant alterations in neural cell proliferation due to astrocyte secreted factors from the Fragile X brain. Highlights: • We studied the proliferation of neural stem and progenitor cells in Fragile X. • We examined the role of astrocyte-secreted factors in neural precursor cell biology. • Astrocyte-secreted factors with differential expression in Fragile X identified. PMID:27242437

Performance of an artificial neural network for vertical root fracture detection: an ex vivo study.

PubMed

Kositbowornchai, Suwadee; Plermkamon, Supattra; Tangkosol, Tawan

2013-04-01

To develop an artificial neural network for vertical root fracture detection. A probabilistic neural network design was used to clarify whether a tooth root was sound or had a vertical root fracture. Two hundred images (50 sound and 150 vertical root fractures) derived from digital radiography--used to train and test the artificial neural network--were divided into three groups according to the number of training and test data sets: 80/120,105/95 and 130/70, respectively. Either training or tested data were evaluated using grey-scale data per line passing through the root. These data were normalized to reduce the grey-scale variance and fed as input data of the neural network. The variance of function in recognition data was calculated between 0 and 1 to select the best performance of neural network. The performance of the neural network was evaluated using a diagnostic test. After testing data under several variances of function, we found the highest sensitivity (98%), specificity (90.5%) and accuracy (95.7%) occurred in Group three, for which the variance of function in recognition data was between 0.025 and 0.005. The neural network designed in this study has sufficient sensitivity, specificity and accuracy to be a model for vertical root fracture detection. © 2012 John Wiley & Sons A/S.

Classification of neural tumors in laboratory rodents, emphasizing the rat.

PubMed

Weber, Klaus; Garman, Robert H; Germann, Paul-Georg; Hardisty, Jerry F; Krinke, Georg; Millar, Peter; Pardo, Ingrid D

2011-01-01

Neoplasms of the nervous system, whether spontaneous or induced, are infrequent in laboratory rodents and very rare in other laboratory animal species. The morphology of neural tumors depends on the intrinsic functions and properties of the cell type, the interactions between the neoplasm and surrounding normal tissue, and regressive changes. The incidence of neural neoplasms varies with sex, location, and age of tumor onset. Although the onset of spontaneous tumor development cannot be established in routine oncogenicity studies, calculations using the time of diagnosis (day of death) have revealed significant differences in tumor biology among different rat strains. In the central nervous system, granular cell tumors (a meningioma variant), followed by glial tumors, are the most common neoplasms in rats, whereas glial cell tumors are observed most frequently in mice. Central nervous system tumors usually affect the brain rather than the spinal cord. Other than adrenal gland pheochromocytomas, the most common neoplasms of the peripheral nervous system are schwannomas. Neural tumors may develop in the central nervous system and peripheral nervous system from other cell lineages (including extraneural elements like adipose tissue and lymphocytes), but such lesions are very rare in laboratory animals.

Hydrogel scaffolds promote neural gene expression and structural reorganization in human astrocyte cultures.

PubMed

Knight, V Bleu; Serrano, Elba E

2017-01-01

Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds. In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel, PuraMatrix™, on human glial cells in vitro . Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene. When the Normal Human Astrocyte (NHA) cell line is grown in a hydrogel matrix environment, the glial cells adopt a structural organization that resembles that of neuronal-glial cocultures, where neurons form clusters that are distinct from the surrounding glia. Statistical analysis of next generation RNA sequencing data uncovered a set of genes that are differentially expressed in the monolayer and matrix hydrogel environments. Functional analysis demonstrated that hydrogel-upregulated genes can be grouped into three broad categories: neuronal differentiation and/or neural plasticity, response to neural insult, and sensory perception. Our results demonstrate that hydrogel biomaterials have the potential to transform human glial cell identity, and may have applications in the repair of damaged brain tissue.

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development.

PubMed

Tan, Yu; Fu, Runqing; Liu, Jiaqiang; Wu, Yong; Wang, Bo; Jiang, Ning; Nie, Ping; Cao, Haifeng; Yang, Zhi; Fang, Bing

2016-07-08

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. Copyright © 2016 Elsevier Inc. All rights reserved.

Chondroitin sulfate effects on neural stem cell differentiation.

PubMed

Canning, David R; Brelsford, Natalie R; Lovett, Neil W

2016-01-01

We have investigated the role chondroitin sulfate has on cell interactions during neural plate formation in the early chick embryo. Using tissue culture isolates from the prospective neural plate, we have measured neural gene expression profiles associated with neural stem cell differentiation. Removal of chondroitin sulfate from stage 4 neural plate tissue leads to altered associations of N-cadherin-positive neural progenitors and causes changes in the normal sequence of neural marker gene expression. Absence of chondroitin sulfate in the neural plate leads to reduced Sox2 expression and is accompanied by an increase in the expression of anterior markers of neural regionalization. Results obtained in this study suggest that the presence of chondroitin sulfate in the anterior chick embryo is instrumental in maintaining cells in the neural precursor state.

Neural decoding of treadmill walking from noninvasive electroencephalographic signals

PubMed Central

Presacco, Alessandro; Goodman, Ronald; Forrester, Larry

2011-01-01

Chronic recordings from ensembles of cortical neurons in primary motor and somatosensory areas in rhesus macaques provide accurate information about bipedal locomotion (Fitzsimmons NA, Lebedev MA, Peikon ID, Nicolelis MA. Front Integr Neurosci 3: 3, 2009). Here we show that the linear and angular kinematics of the ankle, knee, and hip joints during both normal and precision (attentive) human treadmill walking can be inferred from noninvasive scalp electroencephalography (EEG) with decoding accuracies comparable to those from neural decoders based on multiple single-unit activities (SUAs) recorded in nonhuman primates. Six healthy adults were recorded. Participants were asked to walk on a treadmill at their self-selected comfortable speed while receiving visual feedback of their lower limbs (i.e., precision walking), to repeatedly avoid stepping on a strip drawn on the treadmill belt. Angular and linear kinematics of the left and right hip, knee, and ankle joints and EEG were recorded, and neural decoders were designed and optimized with cross-validation procedures. Of note, the optimal set of electrodes of these decoders were also used to accurately infer gait trajectories in a normal walking task that did not require subjects to control and monitor their foot placement. Our results indicate a high involvement of a fronto-posterior cortical network in the control of both precision and normal walking and suggest that EEG signals can be used to study in real time the cortical dynamics of walking and to develop brain-machine interfaces aimed at restoring human gait function. PMID:21768121

Brain activation upon ideal-body media exposure and peer feedback in late adolescent girls.

PubMed

van der Meulen, Mara; Veldhuis, Jolanda; Braams, Barbara R; Peters, Sabine; Konijn, Elly A; Crone, Eveline A

2017-08-01

Media's prevailing thin-body ideal plays a vital role in adolescent girls' body image development, but the co-occurring impact of peer feedback is understudied. The present study used functional magnetic resonance imaging (fMRI) to test media imagery and peer feedback combinations on neural activity related to thin-body ideals. Twenty-four healthy female late adolescents rated precategorized body sizes of bikini models (too thin or normal), directly followed by ostensible peer feedback (too thin or normal). Consistent with prior studies on social feedback processing, results showed increased brain activity in the dorsal medial prefrontal cortex (dmPFC)/anterior cingulate cortex (ACC) and bilateral insula in incongruent situations: when participants rated media models' body size as normal while peer feedback indicated the models as too thin (or vice versa). This effect was stronger for girls with lower self-esteem. A subsequent behavioral study (N = 34 female late adolescents, separate sample) demonstrated that participants changed behavior in the direction of the peer feedback: precategorized normal sized models were rated as too thin more often after receiving too thin peer feedback. This suggests that the neural responses upon peer feedback may influence subsequent choice. Our results show that media-by-peer interactions have pronounced effects on girls' body ideals.

Pattern Adaptation and Normalization Reweighting.

PubMed

Westrick, Zachary M; Heeger, David J; Landy, Michael S

2016-09-21

Adaptation to an oriented stimulus changes both the gain and preferred orientation of neural responses in V1. Neurons tuned near the adapted orientation are suppressed, and their preferred orientations shift away from the adapter. We propose a model in which weights of divisive normalization are dynamically adjusted to homeostatically maintain response products between pairs of neurons. We demonstrate that this adjustment can be performed by a very simple learning rule. Simulations of this model closely match existing data from visual adaptation experiments. We consider several alternative models, including variants based on homeostatic maintenance of response correlations or covariance, as well as feedforward gain-control models with multiple layers, and we demonstrate that homeostatic maintenance of response products provides the best account of the physiological data. Adaptation is a phenomenon throughout the nervous system in which neural tuning properties change in response to changes in environmental statistics. We developed a model of adaptation that combines normalization (in which a neuron's gain is reduced by the summed responses of its neighbors) and Hebbian learning (in which synaptic strength, in this case divisive normalization, is increased by correlated firing). The model is shown to account for several properties of adaptation in primary visual cortex in response to changes in the statistics of contour orientation. Copyright © 2016 the authors 0270-6474/16/369805-12$15.00/0.

Hard to “tune in”: neural mechanisms of live face-to-face interaction with high-functioning autistic spectrum disorder

PubMed Central

Tanabe, Hiroki C.; Kosaka, Hirotaka; Saito, Daisuke N.; Koike, Takahiko; Hayashi, Masamichi J.; Izuma, Keise; Komeda, Hidetsugu; Ishitobi, Makoto; Omori, Masao; Munesue, Toshio; Okazawa, Hidehiko; Wada, Yuji; Sadato, Norihiro

2012-01-01

Persons with autism spectrum disorders (ASD) are known to have difficulty in eye contact (EC). This may make it difficult for their partners during face to face communication with them. To elucidate the neural substrates of live inter-subject interaction of ASD patients and normal subjects, we conducted hyper-scanning functional MRI with 21 subjects with autistic spectrum disorder (ASD) paired with typically-developed (normal) subjects, and with 19 pairs of normal subjects as a control. Baseline EC was maintained while subjects performed real-time joint-attention task. The task-related effects were modeled out, and inter-individual correlation analysis was performed on the residual time-course data. ASD–Normal pairs were less accurate at detecting gaze direction than Normal–Normal pairs. Performance was impaired both in ASD subjects and in their normal partners. The left occipital pole (OP) activation by gaze processing was reduced in ASD subjects, suggesting that deterioration of eye-cue detection in ASD is related to impairment of early visual processing of gaze. On the other hand, their normal partners showed greater activity in the bilateral occipital cortex and the right prefrontal area, indicating a compensatory workload. Inter-brain coherence in the right IFG that was observed in the Normal-Normal pairs (Saito et al., 2010) during EC diminished in ASD–Normal pairs. Intra-brain functional connectivity between the right IFG and right superior temporal sulcus (STS) in normal subjects paired with ASD subjects was reduced compared with in Normal–Normal pairs. This functional connectivity was positively correlated with performance of the normal partners on the eye-cue detection. Considering the integrative role of the right STS in gaze processing, inter-subject synchronization during EC may be a prerequisite for eye cue detection by the normal partner. PMID:23060772

Development of echolocation calls and neural selectivity for echolocation calls in the pallid bat.

PubMed

Razak, Khaleel A; Fuzessery, Zoltan M

2015-10-01

Studies of birdsongs and neural selectivity for songs have provided important insights into principles of concurrent behavioral and auditory system development. Relatively little is known about mammalian auditory system development in terms of vocalizations or other behaviorally relevant sounds. This review suggests echolocating bats are suitable mammalian model systems to understand development of auditory behaviors. The simplicity of echolocation calls with known behavioral relevance and strong neural selectivity provides a platform to address how natural experience shapes cortical receptive field (RF) mechanisms. We summarize recent studies in the pallid bat that followed development of echolocation calls and cortical processing of such calls. We also discuss similar studies in the mustached bat for comparison. These studies suggest: (1) there are different developmental sensitive periods for different acoustic features of the same vocalization. The underlying basis is the capacity for some components of the RF to be modified independent of others. Some RF computations and maps involved in call processing are present even before the cochlea is mature and well before use of echolocation in flight. Others develop over a much longer time course. (2) Normal experience is required not just for refinement, but also for maintenance, of response properties that develop in an experience independent manner. (3) Experience utilizes millisecond range changes in timing of inhibitory and excitatory RF components as substrates to shape vocalization selectivity. We suggest that bat species and call diversity provide a unique opportunity to address developmental constraints in the evolution of neural mechanisms of vocalization processing. © 2014 Wiley Periodicals, Inc.

Development of echolocation calls and neural selectivity for echolocation calls in the pallid bat

PubMed Central

Razak, Khaleel A.; Fuzessery, Zoltan M.

2014-01-01

Studies of birdsongs and neural selectivity for songs have provided important insights into principles of concurrent behavioral and auditory system development. Relatively little is known about mammalian auditory system development in terms of vocalizations, or other behaviorally relevant sounds. This review suggests echolocating bats are suitable mammalian model systems to understand development of auditory behaviors. The simplicity of echolocation calls with known behavioral relevance and strong neural selectivity provides a platform to address how natural experience shapes cortical receptive field (RF) mechanisms. We summarize recent studies in the pallid bat that followed development of echolocation calls and cortical processing of such calls. We also discuss similar studies in the mustached bat for comparison. These studies suggest: (1) there are different developmental sensitive periods for different acoustic features of the same vocalization. The underlying basis is the capacity for some components of the RF to be modified independent of others. Some RF computations and maps involved in call processing are present even before the cochlea is mature and well before use of echolocation in flight. Others develop over a much longer time course. (2) Normal experience is required not just for refinement, but also for maintenance, of response properties that develop in an experience independent manner. (3) Experience utilizes millisecond range changes in timing of inhibitory and excitatory RF components as substrates to shape vocalization selectivity. We suggest that bat species and call diversity provide a unique opportunity to address developmental constraints in the evolution of neural mechanisms of vocalization processing. PMID:25142131

A novel, immortal, and multipotent human neural stem cell line generating functional neurons and oligodendrocytes.

PubMed

De Filippis, Lidia; Lamorte, Giuseppe; Snyder, Evan Y; Malgaroli, Antonio; Vescovi, Angelo L

2007-09-01

The discovery and study of neural stem cells have revolutionized our understanding of the neurogenetic process, and their inherent ability to adopt expansive growth behavior in vitro is of paramount importance for the development of novel therapeutics based on neural cell replacement. Recent advances in high-throughput assays for drug development and gene discovery dictate the need for rapid, reproducible, long-term expansion of human neural stem cells (hNSCs). In this view, the complement of wild-type cell lines currently available is insufficient. Here we report the establishment of a stable human neural stem cell line (immortalized human NSCs [IhNSCs]) by v-myc-mediated immortalization of previously derived wild-type hNSCs. These cells demonstrate three- to fourfold faster proliferation than wild-type cells in response to growth factors but retain rather similar properties, including multipotentiality. By molecular biology, biochemistry, immunocytochemistry, fluorescence microscopy, and electrophysiology, we show that upon growth factor removal, IhNSCs completely downregulate v-myc expression, cease proliferation, and differentiate terminally into three major neural lineages: astrocytes, oligodendrocytes, and neurons. The latter are functional, mature cells displaying clear-cut morphological and physiological features of terminally differentiated neurons, encompassing mostly the GABAergic, glutamatergic, and cholinergic phenotypes. Finally, IhNSCs produce bona fide oligodendrocytes in fractions up to 20% of total cell number. This is in contrast to the negligible propensity of hNSCs to generate oligodendroglia reported so far. Thus, we describe an immortalized hNSC line endowed with the properties of normal hNSCs and suitable for developing the novel, reliable assays and reproducible high-throughput gene and drug screening that are essential in both diagnostics and cell therapy studies.

PROLIFERATION AS A KEY EVENT IN DEVELOPMENTAL TOXICITY: "CHEMICAL SCREENING IN HUMAN NEURAL STEM CELLS USING HIGH CONTENT IMAGING

EPA Science Inventory

New toxicity testing approaches will rely on in vitro assays to assess chemical effects at the cellular and molecular level. Cell proliferation is imperative to normal development, and chemical disruption of this process can be detrimental to the organism. As part of an effort to...

Spatially Compact Neural Clusters in the Dorsal Striatum Encode Locomotion Relevant Information.

PubMed

Barbera, Giovanni; Liang, Bo; Zhang, Lifeng; Gerfen, Charles R; Culurciello, Eugenio; Chen, Rong; Li, Yun; Lin, Da-Ting

2016-10-05

An influential striatal model postulates that neural activities in the striatal direct and indirect pathways promote and inhibit movement, respectively. Normal behavior requires coordinated activity in the direct pathway to facilitate intended locomotion and indirect pathway to inhibit unwanted locomotion. In this striatal model, neuronal population activity is assumed to encode locomotion relevant information. Here, we propose a novel encoding mechanism for the dorsal striatum. We identified spatially compact neural clusters in both the direct and indirect pathways. Detailed characterization revealed similar cluster organization between the direct and indirect pathways, and cluster activities from both pathways were correlated with mouse locomotion velocities. Using machine-learning algorithms, cluster activities could be used to decode locomotion relevant behavioral states and locomotion velocity. We propose that neural clusters in the dorsal striatum encode locomotion relevant information and that coordinated activities of direct and indirect pathway neural clusters are required for normal striatal controlled behavior. VIDEO ABSTRACT. Published by Elsevier Inc.

Accelerating glioblastoma drug discovery: Convergence of patient-derived models, genome editing and phenotypic screening.

PubMed

O'Duibhir, Eoghan; Carragher, Neil O; Pollard, Steven M

2017-04-01

Patients diagnosed with glioblastoma (GBM) continue to face a bleak prognosis. It is critical that new effective therapeutic strategies are developed. GBM stem cells have molecular hallmarks of neural stem and progenitor cells and it is possible to propagate both non-transformed normal neural stem cells and GBM stem cells, in defined, feeder-free, adherent culture. These primary stem cell lines provide an experimental model that is ideally suited to cell-based drug discovery or genetic screens in order to identify tumour-specific vulnerabilities. For many solid tumours, including GBM, the genetic disruptions that drive tumour initiation and growth have now been catalogued. CRISPR/Cas-based genome editing technologies have recently emerged, transforming our ability to functionally annotate the human genome. Genome editing opens prospects for engineering precise genetic changes in normal and GBM-derived neural stem cells, which will provide more defined and reliable genetic models, with critical matched pairs of isogenic cell lines. Generation of more complex alleles such as knock in tags or fluorescent reporters is also now possible. These new cellular models can be deployed in cell-based phenotypic drug discovery (PDD). Here we discuss the convergence of these advanced technologies (iPS cells, neural stem cell culture, genome editing and high content phenotypic screening) and how they herald a new era in human cellular genetics that should have a major impact in accelerating glioblastoma drug discovery. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Prefrontal consolidation supports the attainment of fear memory accuracy.

PubMed

Vieira, Philip A; Lovelace, Jonathan W; Corches, Alex; Rashid, Asim J; Josselyn, Sheena A; Korzus, Edward

2014-08-01

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive. © 2014 Vieira et al.; Published by Cold Spring Harbor Laboratory Press.

Integrating cognitive and peripheral factors in predicting hearing-aid processing effectiveness

PubMed Central

Kates, James M.; Arehart, Kathryn H.; Souza, Pamela E.

2013-01-01

Individual factors beyond the audiogram, such as age and cognitive abilities, can influence speech intelligibility and speech quality judgments. This paper develops a neural network framework for combining multiple subject factors into a single model that predicts speech intelligibility and quality for a nonlinear hearing-aid processing strategy. The nonlinear processing approach used in the paper is frequency compression, which is intended to improve the audibility of high-frequency speech sounds by shifting them to lower frequency regions where listeners with high-frequency loss have better hearing thresholds. An ensemble averaging approach is used for the neural network to avoid the problems associated with overfitting. Models are developed for two subject groups, one having nearly normal hearing and the other mild-to-moderate sloping losses. PMID:25669257

Long-Term Effects of Methylphenidate on Neural Networks Associated with Executive Attention in Children with ADHD: Results from a Longitudinal Functional MRI Study

ERIC Educational Resources Information Center

Konrad, Kerstin; Neufang, Susanne; Fink, Gereon R.; Herpertz-Dahlmann, Beate

2007-01-01

A longitudinal functional MRI study examines the effects of stimulants on neural activity in children with attention-deficit/hyperactivity disorder (ADHD). The results conclude that one year of methylphenidate treatment might be beneficial though insufficient to show normalization of neural correlates of attention.

Arrested neural and advanced mesenchymal differentiation of glioblastoma cells-comparative study with neural progenitors

PubMed Central

2009-01-01

Background Although features of variable differentiation in glioblastoma cell cultures have been reported, a comparative analysis of differentiation properties of normal neural GFAP positive progenitors, and those shown by glioblastoma cells, has not been performed. Methods Following methods were used to compare glioblastoma cells and GFAP+NNP (NHA): exposure to neural differentiation medium, exposure to adipogenic and osteogenic medium, western blot analysis, immunocytochemistry, single cell assay, BrdU incorporation assay. To characterize glioblastoma cells EGFR amplification analysis, LOH/MSI analysis, and P53 nucleotide sequence analysis were performed. Results In vitro differentiation of cancer cells derived from eight glioblastomas was compared with GFAP-positive normal neural progenitors (GFAP+NNP). Prior to exposure to differentiation medium, both types of cells showed similar multilineage phenotype (CD44+/MAP2+/GFAP+/Vimentin+/Beta III-tubulin+/Fibronectin+) and were positive for SOX-2 and Nestin. In contrast to GFAP+NNP, an efficient differentiation arrest was observed in all cell lines isolated from glioblastomas. Nevertheless, a subpopulation of cells isolated from four glioblastomas differentiated after serum-starvation with varying efficiency into derivatives indistinguishable from the neural derivatives of GFAP+NNP. Moreover, the cells derived from a majority of glioblastomas (7 out of 8), as well as GFAP+NNP, showed features of mesenchymal differentiation when exposed to medium with serum. Conclusion Our results showed that stable co-expression of multilineage markers by glioblastoma cells resulted from differentiation arrest. According to our data up to 95% of glioblastoma cells can present in vitro multilineage phenotype. The mesenchymal differentiation of glioblastoma cells is advanced and similar to mesenchymal differentiation of normal neural progenitors GFAP+NNP. PMID:19216795

Maintenance of Mouse Gustatory Terminal Field Organization Is Disrupted following Selective Removal of Peripheral Sodium Salt Taste Activity at Adulthood.

PubMed

Skyberg, Rolf; Sun, Chengsan; Hill, David L

2017-08-09

Neural activity plays a critical role in the development of central circuits in sensory systems. However, the maintenance of these circuits at adulthood is usually not dependent on sensory-elicited neural activity. Recent work in the mouse gustatory system showed that selectively deleting the primary transduction channel for sodium taste, the epithelial sodium channel (ENaC), throughout development dramatically impacted the organization of the central terminal fields of three nerves that carry taste information to the nucleus of the solitary tract. More specifically, deleting ENaCs during development prevented the normal maturation of the fields. The present study was designed to extend these findings by testing the hypothesis that the loss of sodium taste activity impacts the maintenance of the normal adult terminal field organization in male and female mice. To do this, we used an inducible Cre-dependent genetic recombination strategy to delete ENaC function after terminal field maturation occurred. We found that removal of sodium taste neural activity at adulthood resulted in significant reorganization of mature gustatory afferent terminal fields in the nucleus of the solitary tract. Specifically, the chorda tympani and greater superficial petrosal nerve terminal fields were 1.4× and 1.6× larger than age-matched controls, respectively. By contrast, the glossopharyngeal nerve, which is not highly sensitive to sodium taste stimulation, did not undergo terminal field reorganization. These surprising results suggest that gustatory nerve terminal fields remain plastic well into adulthood, which likely impacts central coding of taste information and taste-related behaviors with altered taste experience. SIGNIFICANCE STATEMENT Neural activity plays a major role in the development of sensory circuits in the mammalian brain. However, the importance of sensory-driven activity in maintaining these circuits at adulthood, especially in subcortical structures, appears to be much less. Here, we tested whether the loss of sodium taste activity in adult mice impacts the maintenance of how taste nerves project to the first central relay. We found that specific loss of sodium-elicited taste activity at adulthood produced dramatic and selective reorganization of terminal fields in the brainstem. This demonstrates, for the first time, that taste-elicited activity is necessary for the normal maintenance of central gustatory circuits at adulthood and highlights a level of plasticity not seen in other sensory system subcortical circuits. Copyright © 2017 the authors 0270-6474/17/377619-12$15.00/0.

How normal is grammatical development in the right hemisphere following hemispherectomy? The root infinitive stage and beyond.

PubMed

Curtiss, Susan; de Bode, Stella

2003-08-01

We examined the morphosyntax of eight left hemispherectomized children at two different stages and compared it to MLU-matched normals. We found that the language of the hemispherectomies paralleled that of their MLU matches with respect to the specific morphosyntactic characteristics of each stage. Our findings provide strong evidence for the presence of functional categories in all early grammars and demonstrate that grammatical development, regardless of its neural substrate, is highly constrained by UG and follows a narrowly determined course. We discuss our findings within a neurobiological framework in which etiology defines the integrity of the remaining hemisphere, which in turn, determines its potential for linguistic reorganization and/or acquisition.

Deep convolutional neural network for the automated detection and diagnosis of seizure using EEG signals.

PubMed

Acharya, U Rajendra; Oh, Shu Lih; Hagiwara, Yuki; Tan, Jen Hong; Adeli, Hojjat

2017-09-27

An encephalogram (EEG) is a commonly used ancillary test to aide in the diagnosis of epilepsy. The EEG signal contains information about the electrical activity of the brain. Traditionally, neurologists employ direct visual inspection to identify epileptiform abnormalities. This technique can be time-consuming, limited by technical artifact, provides variable results secondary to reader expertise level, and is limited in identifying abnormalities. Therefore, it is essential to develop a computer-aided diagnosis (CAD) system to automatically distinguish the class of these EEG signals using machine learning techniques. This is the first study to employ the convolutional neural network (CNN) for analysis of EEG signals. In this work, a 13-layer deep convolutional neural network (CNN) algorithm is implemented to detect normal, preictal, and seizure classes. The proposed technique achieved an accuracy, specificity, and sensitivity of 88.67%, 90.00% and 95.00%, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bioimpedance harmonic analysis as a tool to simultaneously assess circulation and nervous control.

PubMed

Mudraya, I S; Revenko, S V; Nesterov, A V; Gavrilov, I Yu; Kirpatovsky, V I

2011-07-01

Multicycle harmonic (Fourier) analysis of bioimpedance was employed to simultaneously assess circulation and neural activity in visceral (rat urinary bladder) and somatic (human finger) organs. The informative value of the first cardiac harmonic of the bladder impedance as an index of bladder circulation is demonstrated. The individual reactions of normal and obstructive bladders in response to infusion cystometry were recorded. The potency of multicycle harmonic analysis of bioimpedance to assess sympathetic and parasympathetic neural control in urinary bladder is discussed. In the human finger, bioimpedance harmonic analysis revealed three periodic components at the rate of the heart beat, respiration and Mayer wave (0.1 Hz), which were observed under normal conditions and during blood flow arrest in the hand. The revealed spectrum peaks were explained by the changes in systemic blood pressure and in regional vascular tone resulting from neural vasomotor control. During normal respiration and circulation, two side cardiac peaks were revealed in a bioimpedance amplitude spectrum, whose amplitude reflected the depth of amplitude respiratory modulation of the cardiac output. During normal breathing, the peaks corresponding to the second and third cardiac harmonics were split, reflecting frequency respiratory modulation of the heart rate. Multicycle harmonic analysis of bioimpedance is a novel potent tool to examine the interaction between the respiratory and cardiovascular system and to simultaneously assess regional circulation and neural influences in visceral and somatic organs.

Modeling Anterior Development in Mice: Diet as Modulator of Risk for Neural Tube Defects

PubMed Central

Kappen, Claudia

2014-01-01

Head morphogenesis is a complex process that is controlled by multiple signaling centers. The most common defects of cranial development are craniofacial defects, such as cleft lip and cleft palate, and neural tube defects, such as anencephaly and encephalocoele in humans. More than 400 genes that contribute to proper neural tube closure have been identified in experimental animals, but only very few causative gene mutations have been identified in humans, supporting the notion that environmental influences are critical. The intrauterine environment is influenced by maternal nutrition, and hence, maternal diet can modulate the risk for cranial and neural tube defects. This article reviews recent progress toward a better understanding of nutrients during pregnancy, with particular focus on mouse models for defective neural tube closure. At least four major patterns of nutrient responses are apparent, suggesting that multiple pathways are involved in the response, and likely in the underlying pathogenesis of the defects. Folic acid has been the most widely studied nutrient, and the diverse responses of the mouse models to folic acid supplementation indicate that folic acid is not universally beneficial, but that the effect is dependent on genetic configuration. If this is the case for other nutrients as well, efforts to prevent neural tube defects with nutritional supplementation may need to become more specifically targeted than previously appreciated. Mouse models are indispensable for a better understanding of nutrient–gene interactions in normal pregnancies, as well as in those affected by metabolic diseases, such as diabetes and obesity. PMID:24124024

A multivariate extension of mutual information for growing neural networks.

PubMed

Ball, Kenneth R; Grant, Christopher; Mundy, William R; Shafer, Timothy J

2017-11-01

Recordings of neural network activity in vitro are increasingly being used to assess the development of neural network activity and the effects of drugs, chemicals and disease states on neural network function. The high-content nature of the data derived from such recordings can be used to infer effects of compounds or disease states on a variety of important neural functions, including network synchrony. Historically, synchrony of networks in vitro has been assessed either by determination of correlation coefficients (e.g. Pearson's correlation), by statistics estimated from cross-correlation histograms between pairs of active electrodes, and/or by pairwise mutual information and related measures. The present study examines the application of Normalized Multiinformation (NMI) as a scalar measure of shared information content in a multivariate network that is robust with respect to changes in network size. Theoretical simulations are designed to investigate NMI as a measure of complexity and synchrony in a developing network relative to several alternative approaches. The NMI approach is applied to these simulations and also to data collected during exposure of in vitro neural networks to neuroactive compounds during the first 12 days in vitro, and compared to other common measures, including correlation coefficients and mean firing rates of neurons. NMI is shown to be more sensitive to developmental effects than first order synchronous and nonsynchronous measures of network complexity. Finally, NMI is a scalar measure of global (rather than pairwise) mutual information in a multivariate network, and hence relies on less assumptions for cross-network comparisons than historical approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage

PubMed Central

Snider, Paige; Olaopa, Michael; Firulli, Anthony B.; Conway, Simon J.

2007-01-01

Although it is well established that transgenic manipulation of mammalian neural crest-related gene expression and microsurgical removal of premigratory chicken and Xenopus embryonic cardiac neural crest progenitors results in a wide spectrum of both structural and functional congenital heart defects, the actual functional mechanism of the cardiac neural crest cells within the heart is poorly understood. Neural crest cell migration and appropriate colonization of the pharyngeal arches and outflow tract septum is thought to be highly dependent on genes that regulate cell-autonomous polarized movement (i.e., gap junctions, cadherins, and noncanonical Wnt1 pathway regulators). Once the migratory cardiac neural crest subpopulation finally reaches the heart, they have traditionally been thought to participate in septation of the common outflow tract into separate aortic and pulmonary arteries. However, several studies have suggested these colonizing neural crest cells may also play additional unexpected roles during cardiovascular development and may even contribute to a crest-derived stem cell population. Studies in both mice and chick suggest they can also enter the heart from the venous inflow as well as the usual arterial outflow region, and may contribute to the adult semilunar and atrioventricular valves as well as part of the cardiac conduction system. Furthermore, although they are not usually thought to give rise to the cardiomyocyte lineage, neural crest cells in the zebrafish (Danio rerio) can contribute to the myocardium and may have different functions in a species-dependent context. Intriguingly, both ablation of chick and Xenopus premigratory neural crest cells, and a transgenic deletion of mouse neural crest cell migration or disruption of the normal mammalian neural crest gene expression profiles, disrupts ventral myocardial function and/or cardiomyocyte proliferation. Combined, this suggests that either the cardiac neural crest secrete factor/s that regulate myocardial proliferation, can signal to the epicardium to subsequently secrete a growth factor/s, or may even contribute directly to the heart. Although there are species differences between mouse, chick, and Xenopus during cardiac neural crest cell morphogenesis, recent data suggest mouse and chick are more similar to each other than to the zebrafish neural crest cell lineage. Several groups have used the genetically defined Pax3 (splotch) mutant mice model to address the role of the cardiac neural crest lineage. Here we review the current literature, the neural crest-related role of the Pax3 transcription factor, and discuss potential function/s of cardiac neural crest-derived cells during cardiovascular developmental remodeling. PMID:17619792

The Sustainable Development Assessment of Reservoir Resettlement Based on a BP Neural Network.

PubMed

Huang, Li; Huang, Jian; Wang, Wei

2018-01-18

Resettlement affects not only the resettlers' production activities and life but also, directly or indirectly, the normal operation of power stations, the sustainable development of the resettlers, and regional social stability. Therefore, a scientific evaluation index system for the sustainable development of reservoir resettlement must be established that fits Chinese national conditions and not only promotes reservoir resettlement research but also improves resettlement practice. This essay builds an evaluation index system for resettlers' sustainable development based on a back-propagation (BP) neural network, which can be adopted in China, taking the resettlement necessitated by step hydropower stations along the Wujiang River cascade as an example. The assessment results show that the resettlement caused by step power stations along the Wujiang River is sustainable, and this evaluation supports the conclusion that national policies and regulations, which are undergoing constant improvement, and resettlement has increasingly improved. The results provide a reference for hydropower reservoir resettlement in developing countries.

The Sustainable Development Assessment of Reservoir Resettlement Based on a BP Neural Network

PubMed Central

Huang, Li; Huang, Jian

2018-01-01

Resettlement affects not only the resettlers’ production activities and life but also, directly or indirectly, the normal operation of power stations, the sustainable development of the resettlers, and regional social stability. Therefore, a scientific evaluation index system for the sustainable development of reservoir resettlement must be established that fits Chinese national conditions and not only promotes reservoir resettlement research but also improves resettlement practice. This essay builds an evaluation index system for resettlers’ sustainable development based on a back-propagation (BP) neural network, which can be adopted in China, taking the resettlement necessitated by step hydropower stations along the Wujiang River cascade as an example. The assessment results show that the resettlement caused by step power stations along the Wujiang River is sustainable, and this evaluation supports the conclusion that national policies and regulations, which are undergoing constant improvement, and resettlement has increasingly improved. The results provide a reference for hydropower reservoir resettlement in developing countries. PMID:29346305

Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells

PubMed Central

Varela, Christine; Denis, Jérôme Alexandre; Polentes, Jérôme; Feyeux, Maxime; Aubert, Sophie; Champon, Benoite; Piétu, Geneviève; Peschanski, Marc; Lefort, Nathalie

2012-01-01

Human pluripotent stem cells offer a limitless source of cells for regenerative medicine. Neural derivatives of human embryonic stem cells (hESCs) are currently being used for cell therapy in 3 clinical trials. However, hESCs are prone to genomic instability, which could limit their clinical utility. Here, we report that neural differentiation of hESCs systematically produced a neural stem cell population that could be propagated for more than 50 passages without entering senescence; this was true for all 6 hESC lines tested. The apparent spontaneous loss of evolution toward normal senescence of somatic cells was associated with a jumping translocation of chromosome 1q. This chromosomal defect has previously been associated with hematologic malignancies and pediatric brain tumors with poor clinical outcome. Neural stem cells carrying the 1q defect implanted into the brains of rats failed to integrate and expand, whereas normal cells engrafted. Our results call for additional quality controls to be implemented to ensure genomic integrity not only of undifferentiated pluripotent stem cells, but also of hESC derivatives that form cell therapy end products, particularly neural lines. PMID:22269325

Implementation of an Adaptive Controller System from Concept to Flight Test

NASA Technical Reports Server (NTRS)

Larson, Richard R.; Burken, John J.; Butler, Bradley S.; Yokum, Steve

2009-01-01

The National Aeronautics and Space Administration Dryden Flight Research Center (Edwards, California) is conducting ongoing flight research using adaptive controller algorithms. A highly modified McDonnell-Douglas NF-15B airplane called the F-15 Intelligent Flight Control System (IFCS) is used to test and develop these algorithms. Modifications to this airplane include adding canards and changing the flight control systems to interface a single-string research controller processor for neural network algorithms. Research goals include demonstration of revolutionary control approaches that can efficiently optimize aircraft performance in both normal and failure conditions and advancement of neural-network-based flight control technology for new aerospace system designs. This report presents an overview of the processes utilized to develop adaptive controller algorithms during a flight-test program, including a description of initial adaptive controller concepts and a discussion of modeling formulation and performance testing. Design finalization led to integration with the system interfaces, verification of the software, validation of the hardware to the requirements, design of failure detection, development of safety limiters to minimize the effect of erroneous neural network commands, and creation of flight test control room displays to maximize human situational awareness; these are also discussed.

Early oestrogens in shaping reproductive networks: evidence for a potential organisational role of oestradiol in female brain development.

PubMed

Bakker, J; Brock, O

2010-07-01

A central tenet of contemporary theories on mammalian brain and behavioural sexual differentiation is that an organisational action of testosterone, secreted by the male's testes, controls male-typical aspects of brain and behavioural development, whereas no active perinatal sex hormone signalling is required for female-typical sexual differentiation. Furthermore, the available evidence suggests that many, although not all, of the perinatal organisational actions of testosterone on the development of the male brain result from the cellular effects of oestradiol formed via neural aromatisation of testosterone. However, a default developmental programme for the female brain has been criticised. Indeed, we review new results obtained in aromatase knockout mice indicating that oestradiol actively contributes to the differentiation of female-typical aspects of brain and behavioural sexual differentiation. Furthermore, we propose that male-typical neural and behavioural differentiation occurs prenatally in genetic males under the influence of oestradiol, which is avoided in foetal genetic females by the neuroprotective actions of alpha-fetoprotein, whereas female-typical neural and behavioural differentiation normally occurs postnatally in genetic females under the influence of oestradiol that is presumably produced by the ovaries.

Relaxed fault-tolerant hardware implementation of neural networks in the presence of multiple transient errors.

PubMed

Mahdiani, Hamid Reza; Fakhraie, Sied Mehdi; Lucas, Caro

2012-08-01

Reliability should be identified as the most important challenge in future nano-scale very large scale integration (VLSI) implementation technologies for the development of complex integrated systems. Normally, fault tolerance (FT) in a conventional system is achieved by increasing its redundancy, which also implies higher implementation costs and lower performance that sometimes makes it even infeasible. In contrast to custom approaches, a new class of applications is categorized in this paper, which is inherently capable of absorbing some degrees of vulnerability and providing FT based on their natural properties. Neural networks are good indicators of imprecision-tolerant applications. We have also proposed a new class of FT techniques called relaxed fault-tolerant (RFT) techniques which are developed for VLSI implementation of imprecision-tolerant applications. The main advantage of RFT techniques with respect to traditional FT solutions is that they exploit inherent FT of different applications to reduce their implementation costs while improving their performance. To show the applicability as well as the efficiency of the RFT method, the experimental results for implementation of a face-recognition computationally intensive neural network and its corresponding RFT realization are presented in this paper. The results demonstrate promising higher performance of artificial neural network VLSI solutions for complex applications in faulty nano-scale implementation environments.

Quantitative Analysis of Cell Migration Using Optical Flow

PubMed Central

Boric, Katica; Orio, Patricio; Viéville, Thierry; Whitlock, Kathleen

2013-01-01

Neural crest cells exhibit dramatic migration behaviors as they populate their distant targets. Using a line of zebrafish expressing green fluorescent protein (sox10:EGFP) in neural crest cells we developed an assay to analyze and quantify cell migration as a population, and use it here to characterize in detail the subtle defects in cell migration caused by ethanol exposure during early development. The challenge was to quantify changes in the in vivo migration of all Sox10:EGFP expressing cells in the visual field of time-lapse movies. To perform this analysis we used an Optical Flow algorithm for motion detection and combined the analysis with a fit to an affine transformation. Through this analysis we detected and quantified significant differences in the cell migrations of Sox10:EGFP positive cranial neural crest populations in ethanol treated versus untreated embryos. Specifically, treatment affected migration by increasing the left-right asymmetry of the migrating cells and by altering the direction of cell movements. Thus, by applying this novel computational analysis, we were able to quantify the movements of populations of cells, allowing us to detect subtle changes in cell behaviors. Because cranial neural crest cells contribute to the formation of the frontal mass these subtle differences may underlie commonly observed facial asymmetries in normal human populations. PMID:23936049

Development of a Neural Network Simulator for Studying the Constitutive Behavior of Structural Composite Materials

DOE PAGES

Na, Hyuntae; Lee, Seung-Yub; Üstündag, Ersan; ...

2013-01-01

This paper introduces a recent development and application of a noncommercial artificial neural network (ANN) simulator with graphical user interface (GUI) to assist in rapid data modeling and analysis in the engineering diffraction field. The real-time network training/simulation monitoring tool has been customized for the study of constitutive behavior of engineering materials, and it has improved data mining and forecasting capabilities of neural networks. This software has been used to train and simulate the finite element modeling (FEM) data for a fiber composite system, both forward and inverse. The forward neural network simulation precisely reduplicates FEM results several orders ofmore » magnitude faster than the slow original FEM. The inverse simulation is more challenging; yet, material parameters can be meaningfully determined with the aid of parameter sensitivity information. The simulator GUI also reveals that output node size for materials parameter and input normalization method for strain data are critical train conditions in inverse network. The successful use of ANN modeling and simulator GUI has been validated through engineering neutron diffraction experimental data by determining constitutive laws of the real fiber composite materials via a mathematically rigorous and physically meaningful parameter search process, once the networks are successfully trained from the FEM database.« less

NFIX Regulates Neural Progenitor Cell Differentiation During Hippocampal Morphogenesis

PubMed Central

Heng, Yee Hsieh Evelyn; McLeay, Robert C.; Harvey, Tracey J.; Smith, Aaron G.; Barry, Guy; Cato, Kathleen; Plachez, Céline; Little, Erica; Mason, Sharon; Dixon, Chantelle; Gronostajski, Richard M.; Bailey, Timothy L.; Richards, Linda J.; Piper, Michael

2014-01-01

Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix−/− mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix−/− mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix−/− mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure. PMID:23042739

Cannabinoid mitigation of neuronal morphological change important to development and learning: insight from a zebra finch model of psychopharmacology.

PubMed

Soderstrom, Ken; Gilbert, Marcoita T

2013-03-19

Normal CNS development proceeds through late-postnatal stages of adolescent development. The activity-dependence of this development underscores the significance of CNS-active drug exposure prior to completion of brain maturation. Exogenous modulation of signaling important in regulating normal development is of particular concern. This mini-review presents a summary of the accumulated behavioral, physiological and biochemical evidence supporting such a key regulatory role for endocannabinoid signaling during late-postnatal CNS development. Our focus is on the data obtained using a unique zebra finch model of developmental psychopharmacology. This animal has allowed investigation of neuronal morphological effects essential to establishment and maintenance of neural circuitry, including processes related to synaptogenesis and dendritic spine dynamics. Altered neurophysiology that follows exogenous cannabinoid exposure during adolescent development has the potential to persistently alter cognition, learning and memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Detecting central fixation by means of artificial neural networks in a pediatric vision screener using retinal birefringence scanning.

PubMed

Gramatikov, Boris I

2017-04-27

Reliable detection of central fixation and eye alignment is essential in the diagnosis of amblyopia ("lazy eye"), which can lead to blindness. Our lab has developed and reported earlier a pediatric vision screener that performs scanning of the retina around the fovea and analyzes changes in the polarization state of light as the scan progresses. Depending on the direction of gaze and the instrument design, the screener produces several signal frequencies that can be utilized in the detection of central fixation. The objective of this study was to compare artificial neural networks with classical statistical methods, with respect to their ability to detect central fixation reliably. A classical feedforward, pattern recognition, two-layer neural network architecture was used, consisting of one hidden layer and one output layer. The network has four inputs, representing normalized spectral powers at four signal frequencies generated during retinal birefringence scanning. The hidden layer contains four neurons. The output suggests presence or absence of central fixation. Backpropagation was used to train the network, using the gradient descent algorithm and the cross-entropy error as the performance function. The network was trained, validated and tested on a set of controlled calibration data obtained from 600 measurements from ten eyes in a previous study, and was additionally tested on a clinical set of 78 eyes, independently diagnosed by an ophthalmologist. In the first part of this study, a neural network was designed around the calibration set. With a proper architecture and training, the network provided performance that was comparable to classical statistical methods, allowing perfect separation between the central and paracentral fixation data, with both the sensitivity and the specificity of the instrument being 100%. In the second part of the study, the neural network was applied to the clinical data. It allowed reliable separation between normal subjects and affected subjects, its accuracy again matching that of the statistical methods. With a proper choice of a neural network architecture and a good, uncontaminated training data set, the artificial neural network can be an efficient classification tool for detecting central fixation based on retinal birefringence scanning.

Computational neuroanatomy: ontology-based representation of neural components and connectivity.

PubMed

Rubin, Daniel L; Talos, Ion-Florin; Halle, Michael; Musen, Mark A; Kikinis, Ron

2009-02-05

A critical challenge in neuroscience is organizing, managing, and accessing the explosion in neuroscientific knowledge, particularly anatomic knowledge. We believe that explicit knowledge-based approaches to make neuroscientific knowledge computationally accessible will be helpful in tackling this challenge and will enable a variety of applications exploiting this knowledge, such as surgical planning. We developed ontology-based models of neuroanatomy to enable symbolic lookup, logical inference and mathematical modeling of neural systems. We built a prototype model of the motor system that integrates descriptive anatomic and qualitative functional neuroanatomical knowledge. In addition to modeling normal neuroanatomy, our approach provides an explicit representation of abnormal neural connectivity in disease states, such as common movement disorders. The ontology-based representation encodes both structural and functional aspects of neuroanatomy. The ontology-based models can be evaluated computationally, enabling development of automated computer reasoning applications. Neuroanatomical knowledge can be represented in machine-accessible format using ontologies. Computational neuroanatomical approaches such as described in this work could become a key tool in translational informatics, leading to decision support applications that inform and guide surgical planning and personalized care for neurological disease in the future.

Planar induction of anteroposterior pattern in the developing central nervous system of Xenopus laevis

NASA Technical Reports Server (NTRS)

Doniach, T.; Phillips, C. R.; Gerhart, J. C.

1992-01-01

It has long been thought that anteroposterior (A-P) pattern in the vertebrate central nervous system is induced in the embryo's dorsal ectoderm exclusively by signals passing vertically from underlying, patterned dorsal mesoderm. Explants from early gastrulae of the frog Xenopus laevis were prepared in which vertical contact between dorsal ectoderm and mesoderm was prevented but planar contact was maintained. In these, four position-specific neural markers (engrailed-2, Krox-20, XlHbox 1, and XlHbox 6) were expressed in the ectoderm in the same A-P order as in the embryo. Thus, planar signals alone, following a path available in the normal embryo, can induce A-P neural pattern.

An auditory-neuroscience perspective on the development of selective mutism.

PubMed

Henkin, Yael; Bar-Haim, Yair

2015-04-01

Selective mutism (SM) is a relatively rare psychiatric disorder of childhood characterized by consistent inability to speak in specific social situations despite the ability to speak normally in others. SM typically involves severe impairments in social and academic functioning. Common complications include school failure, social difficulties in the peer group, and aggravated intra-familial relationships. Although SM has been described in the medical and psychological literatures for many years, the potential underlying neural basis of the disorder has only recently been explored. Here we explore the potential role of specific auditory neural mechanisms in the psychopathology of SM and discuss possible implications for treatment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Deep convolutional neural networks for classifying head and neck cancer using hyperspectral imaging

NASA Astrophysics Data System (ADS)

Halicek, Martin; Lu, Guolan; Little, James V.; Wang, Xu; Patel, Mihir; Griffith, Christopher C.; El-Deiry, Mark W.; Chen, Amy Y.; Fei, Baowei

2017-06-01

Surgical cancer resection requires an accurate and timely diagnosis of the cancer margins in order to achieve successful patient remission. Hyperspectral imaging (HSI) has emerged as a useful, noncontact technique for acquiring spectral and optical properties of tissue. A convolutional neural network (CNN) classifier is developed to classify excised, squamous-cell carcinoma, thyroid cancer, and normal head and neck tissue samples using HSI. The CNN classification was validated by the manual annotation of a pathologist specialized in head and neck cancer. The preliminary results of 50 patients indicate the potential of HSI and deep learning for automatic tissue-labeling of surgical specimens of head and neck patients.

Static facial expression recognition with convolution neural networks

NASA Astrophysics Data System (ADS)

Zhang, Feng; Chen, Zhong; Ouyang, Chao; Zhang, Yifei

2018-03-01

Facial expression recognition is a currently active research topic in the fields of computer vision, pattern recognition and artificial intelligence. In this paper, we have developed a convolutional neural networks (CNN) for classifying human emotions from static facial expression into one of the seven facial emotion categories. We pre-train our CNN model on the combined FER2013 dataset formed by train, validation and test set and fine-tune on the extended Cohn-Kanade database. In order to reduce the overfitting of the models, we utilized different techniques including dropout and batch normalization in addition to data augmentation. According to the experimental result, our CNN model has excellent classification performance and robustness for facial expression recognition.

Dynamic Divisive Normalization Predicts Time-Varying Value Coding in Decision-Related Circuits

PubMed Central

LoFaro, Thomas; Webb, Ryan; Glimcher, Paul W.

2014-01-01

Normalization is a widespread neural computation, mediating divisive gain control in sensory processing and implementing a context-dependent value code in decision-related frontal and parietal cortices. Although decision-making is a dynamic process with complex temporal characteristics, most models of normalization are time-independent and little is known about the dynamic interaction of normalization and choice. Here, we show that a simple differential equation model of normalization explains the characteristic phasic-sustained pattern of cortical decision activity and predicts specific normalization dynamics: value coding during initial transients, time-varying value modulation, and delayed onset of contextual information. Empirically, we observe these predicted dynamics in saccade-related neurons in monkey lateral intraparietal cortex. Furthermore, such models naturally incorporate a time-weighted average of past activity, implementing an intrinsic reference-dependence in value coding. These results suggest that a single network mechanism can explain both transient and sustained decision activity, emphasizing the importance of a dynamic view of normalization in neural coding. PMID:25429145

Design of neural networks for classification of remotely sensed imagery

NASA Technical Reports Server (NTRS)

Chettri, Samir R.; Cromp, Robert F.; Birmingham, Mark

1992-01-01

Classification accuracies of a backpropagation neural network are discussed and compared with a maximum likelihood classifier (MLC) with multivariate normal class models. We have found that, because of its nonparametric nature, the neural network outperforms the MLC in this area. In addition, we discuss techniques for constructing optimal neural nets on parallel hardware like the MasPar MP-1 currently at GSFC. Other important discussions are centered around training and classification times of the two methods, and sensitivity to the training data. Finally, we discuss future work in the area of classification and neural nets.

A Hybrid Spectral Clustering and Deep Neural Network Ensemble Algorithm for Intrusion Detection in Sensor Networks

PubMed Central

Ma, Tao; Wang, Fen; Cheng, Jianjun; Yu, Yang; Chen, Xiaoyun

2016-01-01

The development of intrusion detection systems (IDS) that are adapted to allow routers and network defence systems to detect malicious network traffic disguised as network protocols or normal access is a critical challenge. This paper proposes a novel approach called SCDNN, which combines spectral clustering (SC) and deep neural network (DNN) algorithms. First, the dataset is divided into k subsets based on sample similarity using cluster centres, as in SC. Next, the distance between data points in a testing set and the training set is measured based on similarity features and is fed into the deep neural network algorithm for intrusion detection. Six KDD-Cup99 and NSL-KDD datasets and a sensor network dataset were employed to test the performance of the model. These experimental results indicate that the SCDNN classifier not only performs better than backpropagation neural network (BPNN), support vector machine (SVM), random forest (RF) and Bayes tree models in detection accuracy and the types of abnormal attacks found. It also provides an effective tool of study and analysis of intrusion detection in large networks. PMID:27754380

A Hybrid Spectral Clustering and Deep Neural Network Ensemble Algorithm for Intrusion Detection in Sensor Networks.

PubMed

Ma, Tao; Wang, Fen; Cheng, Jianjun; Yu, Yang; Chen, Xiaoyun

2016-10-13

The development of intrusion detection systems (IDS) that are adapted to allow routers and network defence systems to detect malicious network traffic disguised as network protocols or normal access is a critical challenge. This paper proposes a novel approach called SCDNN, which combines spectral clustering (SC) and deep neural network (DNN) algorithms. First, the dataset is divided into k subsets based on sample similarity using cluster centres, as in SC. Next, the distance between data points in a testing set and the training set is measured based on similarity features and is fed into the deep neural network algorithm for intrusion detection. Six KDD-Cup99 and NSL-KDD datasets and a sensor network dataset were employed to test the performance of the model. These experimental results indicate that the SCDNN classifier not only performs better than backpropagation neural network (BPNN), support vector machine (SVM), random forest (RF) and Bayes tree models in detection accuracy and the types of abnormal attacks found. It also provides an effective tool of study and analysis of intrusion detection in large networks.

Prediction of forced expiratory volume in pulmonary function test using radial basis neural networks and k-means clustering.

PubMed

Manoharan, Sujatha C; Ramakrishnan, Swaminathan

2009-10-01

In this work, prediction of forced expiratory volume in pulmonary function test, carried out using spirometry and neural networks is presented. The pulmonary function data were recorded from volunteers using commercial available flow volume spirometer in standard acquisition protocol. The Radial Basis Function neural networks were used to predict forced expiratory volume in 1 s (FEV1) from the recorded flow volume curves. The optimal centres of the hidden layer of radial basis function were determined by k-means clustering algorithm. The performance of the neural network model was evaluated by computing their prediction error statistics of average value, standard deviation, root mean square and their correlation with the true data for normal, restrictive and obstructive cases. Results show that the adopted neural networks are capable of predicting FEV1 in both normal and abnormal cases. Prediction accuracy was more in obstructive abnormality when compared to restrictive cases. It appears that this method of assessment is useful in diagnosing the pulmonary abnormalities with incomplete data and data with poor recording.

Diagnosis of Diabetes Mellitus by Extraction of Morphological Features of Red Blood Cells Using an Artificial Neural Network.

PubMed

Palanisamy, Vinupritha; Mariamichael, Anburajan

2016-10-01

Background and Aim: Diabetes mellitus is a metabolic disorder characterized by varying hyperglycemias either due to insufficient secretion of insulin by the pancreas or improper utilization of glucose. The study was aimed to investigate the association of morphological features of erythrocytes among normal and diabetic subjects and its gender-based changes and thereby to develop a computer aided tool to diagnose diabetes using features extracted from RBC. Materials and Methods: The study involved 138 normal and 144 diabetic subjects. The blood was drawn from the subjects and the blood smear prepared was digitized using Zeiss fluorescent microscope. The digitized images were pre-processed and texture segmentation was performed to extract the various morphological features. The Pearson correlation test was performed and subsequently, classification of subjects as normal and diabetes was carried out by a neural network classifier based on the features that demonstrated significance at the level of P <0.05. Result: The proposed system demonstrated an overall accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 93.3, 93.71, 92.8, 93.1 and 93.5% respectively. Conclusion: The morphological features exhibited a statistically significant difference (P<0.01) between the normal and diabetic cells, suggesting that it could be helpful in the diagnosis of Diabetes mellitus using a computer aided system. © Georg Thieme Verlag KG Stuttgart · New York.

Automated embolic signal detection using Deep Convolutional Neural Network.

PubMed

Sombune, Praotasna; Phienphanich, Phongphan; Phuechpanpaisal, Sutanya; Muengtaweepongsa, Sombat; Ruamthanthong, Anuchit; Tantibundhit, Charturong

2017-07-01

This work investigated the potential of Deep Neural Network in detection of cerebral embolic signal (ES) from transcranial Doppler ultrasound (TCD). The resulting system is aimed to couple with TCD devices in diagnosing a risk of stroke in real-time with high accuracy. The Adaptive Gain Control (AGC) approach developed in our previous study is employed to capture suspected ESs in real-time. By using spectrograms of the same TCD signal dataset as that of our previous work as inputs and the same experimental setup, Deep Convolutional Neural Network (CNN), which can learn features while training, was investigated for its ability to bypass the traditional handcrafted feature extraction and selection process. Extracted feature vectors from the suspected ESs are later determined whether they are of an ES, artifact (AF) or normal (NR) interval. The effectiveness of the developed system was evaluated over 19 subjects going under procedures generating emboli. The CNN-based system could achieve in average of 83.0% sensitivity, 80.1% specificity, and 81.4% accuracy, with considerably much less time consumption in development. The certainly growing set of training samples and computational resources will contribute to high performance. Besides having potential use in various clinical ES monitoring settings, continuation of this promising study will benefit developments of wearable applications by leveraging learnable features to serve demographic differentials.

Hard to Swallow: Developmental Biological Insights into Pediatric Dysphagia

PubMed Central

LaMantia, Anthony-Samuel; Moody, Sally A.; Maynard, Thomas M.; Karpinski, Beverly A.; Zohn, Irene E.; Mendelowitz, David; Lee, Norman H.; Popratiloff, Anastas

2015-01-01

Pediatric dysphagia—feeding and swallowing difficulties that begin at birth, last throughout childhood, and continue into maturity—is one of the most common, least understood complications in children with developmental disorders. We argue that a major cause of pediatric dysphagia is altered hindbrain patterning during pre-natal development. Such changes can compromise craniofacial structures including oropharyngeal muscles and skeletal elements as well as motor and sensory circuits necessary for normal feeding and swallowing. Animal models of developmental disorders that include pediatric dysphagia in their phenotypic spectrum can provide mechanistic insight into pathogenesis of feeding and swallowing difficulties. A fairly common human genetic developmental disorder, DiGeorge/22q11.2 Deletion Syndrome (22q11DS) includes a substantial incidence of pediatric dysphagia in its phenotypic spectrum. Infant mice carrying a parallel deletion to 22q11DS patients have feeding and swallowing difficulties. Altered hindbrain patterning, neural crest migration, craniofacial malformations, and changes in cranial nerve growth prefigure these difficulties. Thus, in addition to craniofacial and pharyngeal anomalies that arise independently of altered neural development, pediatric dysphagia may reflect disrupted hindbrain patterning and its impact on neural circuit development critical for feeding and swallowing. The mechanisms that disrupt hindbrain patterning and circuitry may provide a foundation to develop novel therapeutic approaches for improved clinical management of pediatric dysphagia. PMID:26554723

Vestigial-like 3 is a novel Ets1 interacting partner and regulates trigeminal nerve formation and cranial neural crest migration

PubMed Central

Simon, Emilie; Thézé, Nadine; Fédou, Sandrine; Thiébaud, Pierre

2017-01-01

ABSTRACT Drosophila Vestigial is the founding member of a protein family containing a highly conserved domain, called Tondu, which mediates their interaction with members of the TEAD family of transcription factors (Scalloped in Drosophila). In Drosophila, the Vestigial/Scalloped complex controls wing development by regulating the expression of target genes through binding to MCAT sequences. In vertebrates, there are four Vestigial-like genes, the functions of which are still not well understood. Here, we describe the regulation and function of vestigial-like 3 (vgll3) during Xenopus early development. A combination of signals, including FGF8, Wnt8a, Hoxa2, Hoxb2 and retinoic acid, limits vgll3 expression to hindbrain rhombomere 2. We show that vgll3 regulates trigeminal placode and nerve formation and is required for normal neural crest development by affecting their migration and adhesion properties. At the molecular level, vgll3 is a potent activator of pax3, zic1, Wnt and FGF, which are important for brain patterning and neural crest cell formation. Vgll3 interacts in the embryo with Tead proteins but unexpectedly with Ets1, with which it is able to stimulate a MCAT driven luciferase reporter gene. Our findings highlight a critical function for vgll3 in vertebrate early development. PMID:28870996

Target structures in the cochlea for infrared neural stimulation (INS)

NASA Astrophysics Data System (ADS)

Young, Hunter; Tan, Xiaodong; Richter, Claus-Peter

2014-03-01

Spatial selective infrared neural stimulation has potential to improve neural prostheses, including cochlear implants. The heating of a confined target volume depolarizes the cell membrane and results in an action potential. Tissue heating may also result in the generation of a stress relaxation wave causing mechanical stimulation of hair cells in the cochlea, creating an optoacoustic response. Data are presented that quantify the effect of an acoustical stimulus (noise masker) on the response obtained with INS in normal hearing, and chronic deaf animals. While in normal hearing animals an acoustic masker can reduce the response to INS, in chronic deaf animals this effect has not been detected. The responses to INS remain stable following the different degrees of cochlear damage.

A novel wavelet neural network based pathological stage detection technique for an oral precancerous condition

PubMed Central

Paul, R R; Mukherjee, A; Dutta, P K; Banerjee, S; Pal, M; Chatterjee, J; Chaudhuri, K; Mukkerjee, K

2005-01-01

Aim: To describe a novel neural network based oral precancer (oral submucous fibrosis; OSF) stage detection method. Method: The wavelet coefficients of transmission electron microscopy images of collagen fibres from normal oral submucosa and OSF tissues were used to choose the feature vector which, in turn, was used to train the artificial neural network. Results: The trained network was able to classify normal and oral precancer stages (less advanced and advanced) after obtaining the image as an input. Conclusions: The results obtained from this proposed technique were promising and suggest that with further optimisation this method could be used to detect and stage OSF, and could be adapted for other conditions. PMID:16126873

The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival

PubMed Central

Dworkin, Sebastian; Boglev, Yeliz; Owens, Harley; Goldie, Stephen J.

2016-01-01

Craniofacial defects (CFD) are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog (Shh), a vertebrate orthologue of Drosophila hedgehog, is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla) and lower jaw (mandible). PMID:29615588

The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival.

PubMed

Dworkin, Sebastian; Boglev, Yeliz; Owens, Harley; Goldie, Stephen J

2016-08-03

Craniofacial defects (CFD) are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog ( Shh ), a vertebrate orthologue of Drosophila hedgehog , is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla) and lower jaw (mandible).

Neural plasticity and its initiating conditions in tinnitus.

PubMed

Roberts, L E

2018-03-01

Deafferentation caused by cochlear pathology (which can be hidden from the audiogram) activates forms of neural plasticity in auditory pathways, generating tinnitus and its associated conditions including hyperacusis. This article discusses tinnitus mechanisms and suggests how these mechanisms may relate to those involved in normal auditory information processing. Research findings from animal models of tinnitus and from electromagnetic imaging of tinnitus patients are reviewed which pertain to the role of deafferentation and neural plasticity in tinnitus and hyperacusis. Auditory neurons compensate for deafferentation by increasing their input/output functions (gain) at multiple levels of the auditory system. Forms of homeostatic plasticity are believed to be responsible for this neural change, which increases the spontaneous and driven activity of neurons in central auditory structures in animals expressing behavioral evidence of tinnitus. Another tinnitus correlate, increased neural synchrony among the affected neurons, is forged by spike-timing-dependent neural plasticity in auditory pathways. Slow oscillations generated by bursting thalamic neurons verified in tinnitus animals appear to modulate neural plasticity in the cortex, integrating tinnitus neural activity with information in brain regions supporting memory, emotion, and consciousness which exhibit increased metabolic activity in tinnitus patients. The latter process may be induced by transient auditory events in normal processing but it persists in tinnitus, driven by phantom signals from the auditory pathway. Several tinnitus therapies attempt to suppress tinnitus through plasticity, but repeated sessions will likely be needed to prevent tinnitus activity from returning owing to deafferentation as its initiating condition.

Impaired activity-dependent neural circuit assembly and refinement in autism spectrum disorder genetic models

PubMed Central

Doll, Caleb A.; Broadie, Kendal

2014-01-01

Early-use activity during circuit-specific critical periods refines brain circuitry by the coupled processes of eliminating inappropriate synapses and strengthening maintained synapses. We theorize these activity-dependent (A-D) developmental processes are specifically impaired in autism spectrum disorders (ASDs). ASD genetic models in both mouse and Drosophila have pioneered our insights into normal A-D neural circuit assembly and consolidation, and how these developmental mechanisms go awry in specific genetic conditions. The monogenic fragile X syndrome (FXS), a common cause of heritable ASD and intellectual disability, has been particularly well linked to defects in A-D critical period processes. The fragile X mental retardation protein (FMRP) is positively activity-regulated in expression and function, in turn regulates excitability and activity in a negative feedback loop, and appears to be required for the A-D remodeling of synaptic connectivity during early-use critical periods. The Drosophila FXS model has been shown to functionally conserve the roles of human FMRP in synaptogenesis, and has been centrally important in generating our current mechanistic understanding of the FXS disease state. Recent advances in Drosophila optogenetics, transgenic calcium reporters, highly-targeted transgenic drivers for individually-identified neurons, and a vastly improved connectome of the brain are now being combined to provide unparalleled opportunities to both manipulate and monitor A-D processes during critical period brain development in defined neural circuits. The field is now poised to exploit this new Drosophila transgenic toolbox for the systematic dissection of A-D mechanisms in normal versus ASD brain development, particularly utilizing the well-established Drosophila FXS disease model. PMID:24570656

Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marks, Shawn M.; Lockhart, Samuel N.; Baker, Suzanne L.

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turnmore » associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer’s disease-related protein aggregation as an underlying mechanism of age-related memory impairment.« less

Marginalization in neural circuits with divisive normalization

PubMed Central

Beck, J.M.; Latham, P.E.; Pouget, A.

2011-01-01

A wide range of computations performed by the nervous system involves a type of probabilistic inference known as marginalization. This computation comes up in seemingly unrelated tasks, including causal reasoning, odor recognition, motor control, visual tracking, coordinate transformations, visual search, decision making, and object recognition, to name just a few. The question we address here is: how could neural circuits implement such marginalizations? We show that when spike trains exhibit a particular type of statistics – associated with constant Fano factors and gain-invariant tuning curves, as is often reported in vivo – some of the more common marginalizations can be achieved with networks that implement a quadratic nonlinearity and divisive normalization, the latter being a type of nonlinear lateral inhibition that has been widely reported in neural circuits. Previous studies have implicated divisive normalization in contrast gain control and attentional modulation. Our results raise the possibility that it is involved in yet another, highly critical, computation: near optimal marginalization in a remarkably wide range of tasks. PMID:22031877

Investigating Models of Social Development Using a Humanoid Robot

DTIC Science & Technology

1998-01-01

robot interaction and cooper- and neural models of spinal motor neurons (Williamson ation (Takanishi, Hirano & Sato 1998, Morita, Shibuya 1996...etiology and behavioral manifestations of pervasive de- Individuals with autism tend to have normal sensory velopmental disorders such as autism and...grasp the implications of this information. Wlile interested in joint attention both as an explanation the deficits of autism certainly cover many other

Network Analysis: Applications for the Developing Brain

PubMed Central

Chu-Shore, Catherine J.; Kramer, Mark A.; Bianchi, Matt T.; Caviness, Verne S.; Cash, Sydney S.

2011-01-01

Development of the human brain follows a complex trajectory of age-specific anatomical and physiological changes. The application of network analysis provides an illuminating perspective on the dynamic interregional and global properties of this intricate and complex system. Here, we provide a critical synopsis of methods of network analysis with a focus on developing brain networks. After discussing basic concepts and approaches to network analysis, we explore the primary events of anatomical cortical development from gestation through adolescence. Upon this framework, we describe early work revealing the evolution of age-specific functional brain networks in normal neurodevelopment. Finally, we review how these relationships can be altered in disease and perhaps even rectified with treatment. While this method of description and inquiry remains in early form, there is already substantial evidence that the application of network models and analysis to understanding normal and abnormal human neural development holds tremendous promise for future discovery. PMID:21303762

Does fractality in heart rate variability indicate the development of fetal neural processes?

NASA Astrophysics Data System (ADS)

Echeverría, J. C.; Woolfson, M. S.; Crowe, J. A.; Hayes-Gill, B. R.; Piéri, Jean F.; Spencer, C. J.; James, D. K.

2004-10-01

By using an improved detrended fluctuation analysis we studied the scaling behaviour of 53 long-term series of fetal heart rate fluctuations. Our results suggest that fractality begins to arise around 24 weeks of normal human gestation and that this condition, showing some additional developments, seems to be preserved during gestation. This may provide new evidence of a role played by cortical-to-subcortical pathways in the long-term fractal nature of heart rate variability data.

Lack of a p21waf1/cip -dependent G1/S checkpoint in neural stem and progenitor cells after DNA damage in vivo.

PubMed

Roque, Telma; Haton, Céline; Etienne, Olivier; Chicheportiche, Alexandra; Rousseau, Laure; Martin, Ludovic; Mouthon, Marc-André; Boussin, François D

2012-03-01

The cyclin-dependent kinase inhibitor p21(waf1/cip) mediates the p53-dependent G1/S checkpoint, which is generally considered to be a critical requirement to maintain genomic stability after DNA damage. We used staggered 5-ethynyl-2'deoxyuridine/5-bromo-2'-deoxyuridine double-labeling in vivo to investigate the cell cycle progression and the role of p21(waf1/cip) in the DNA damage response of neural stem and progenitor cells (NSPCs) after exposure of the developing mouse cortex to ionizing radiation. We observed a radiation-induced p21-dependent apoptotic response in migrating postmitotic cortical cells. However, neural stem and progenitor cells (NSPCs) did not initiate a p21(waf1/cip1) -dependent G1/S block and continued to enter S-phase at a similar rate to the non-irradiated controls. The G1/S checkpoint is not involved in the mechanisms underlying the faithful transmission of the NSPC genome and/or the elimination of critically damaged cells. These processes typically involve intra-S and G2/M checkpoints that are rapidly activated after irradiation. p21 is normally repressed in neural cells during brain development except at the G1 to G0 transition. Lack of activation of a G1/S checkpoint and apoptosis of postmitotic migrating cells after DNA damage appear to depend on the expression of p21 in neural cells, since substantial cell-to-cell variations are found in the irradiated cortex. This suggests that repression of p21 during brain development prevents the induction of the G1/S checkpoint after DNA damage. Copyright © 2011 AlphaMed Press.

Neural net classification of liver ultrasonogram for quantitative evaluation of diffuse liver disease

NASA Astrophysics Data System (ADS)

Lee, Dong Hyuk; Kim, JongHyo; Kim, Hee C.; Lee, Yong W.; Min, Byong Goo

1997-04-01

There have been a number of studies on the quantitative evaluation of diffuse liver disease by using texture analysis technique. However, the previous studies have been focused on the classification between only normal and abnormal pattern based on textural properties, resulting in lack of clinically useful information about the progressive status of liver disease. Considering our collaborative research experience with clinical experts, we judged that not only texture information but also several shape properties are necessary in order to successfully classify between various states of disease with liver ultrasonogram. Nine image parameters were selected experimentally. One of these was texture parameter and others were shape parameters measured as length, area and curvature. We have developed a neural-net algorithm that classifies liver ultrasonogram into 9 categories of liver disease: 3 main category and 3 sub-steps for each. Nine parameters were collected semi- automatically from the user by using graphical user interface tool, and then processed to give a grade for each parameter. Classifying algorithm consists of two steps. At the first step, each parameter was graded into pre-defined levels using neural network. in the next step, neural network classifier determined disease status using graded nine parameters. We implemented a PC based computer-assist diagnosis workstation and installed it in radiology department of Seoul National University Hospital. Using this workstation we collected 662 cases during 6 months. Some of these were used for training and others were used for evaluating accuracy of the developed algorithm. As a conclusion, a liver ultrasonogram classifying algorithm was developed using both texture and shape parameters and neural network classifier. Preliminary results indicate that the proposed algorithm is useful for evaluation of diffuse liver disease.

Feed-Forward Neural Network Prediction of the Mechanical Properties of Sandcrete Materials

PubMed Central

Asteris, Panagiotis G.; Roussis, Panayiotis C.; Douvika, Maria G.

2017-01-01

This work presents a soft-sensor approach for estimating critical mechanical properties of sandcrete materials. Feed-forward (FF) artificial neural network (ANN) models are employed for building soft-sensors able to predict the 28-day compressive strength and the modulus of elasticity of sandcrete materials. To this end, a new normalization technique for the pre-processing of data is proposed. The comparison of the derived results with the available experimental data demonstrates the capability of FF ANNs to predict with pinpoint accuracy the mechanical properties of sandcrete materials. Furthermore, the proposed normalization technique has been proven effective and robust compared to other normalization techniques available in the literature. PMID:28598400

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Yu, E-mail: tanyu2048@163.com; Fu, Runqing, E-mail: furunqing@sjtu.edu.cn; Liu, Jiaqiang, E-mail: liujqmj@163.com

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of themore » craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.« less

Losing the music: aging affects the perception and subcortical neural representation of musical harmony.

PubMed

Bones, Oliver; Plack, Christopher J

2015-03-04

When two musical notes with simple frequency ratios are played simultaneously, the resulting musical chord is pleasing and evokes a sense of resolution or "consonance". Complex frequency ratios, on the other hand, evoke feelings of tension or "dissonance". Consonance and dissonance form the basis of harmony, a central component of Western music. In earlier work, we provided evidence that consonance perception is based on neural temporal coding in the brainstem (Bones et al., 2014). Here, we show that for listeners with clinically normal hearing, aging is associated with a decline in both the perceptual distinction and the distinctiveness of the neural representations of different categories of two-note chords. Compared with younger listeners, older listeners rated consonant chords as less pleasant and dissonant chords as more pleasant. Older listeners also had less distinct neural representations of consonant and dissonant chords as measured using a Neural Consonance Index derived from the electrophysiological "frequency-following response." The results withstood a control for the effect of age on general affect, suggesting that different mechanisms are responsible for the perceived pleasantness of musical chords and affective voices and that, for listeners with clinically normal hearing, age-related differences in consonance perception are likely to be related to differences in neural temporal coding. Copyright © 2015 Bones and Plack.

Losing the Music: Aging Affects the Perception and Subcortical Neural Representation of Musical Harmony

PubMed Central

Plack, Christopher J.

2015-01-01

When two musical notes with simple frequency ratios are played simultaneously, the resulting musical chord is pleasing and evokes a sense of resolution or “consonance”. Complex frequency ratios, on the other hand, evoke feelings of tension or “dissonance”. Consonance and dissonance form the basis of harmony, a central component of Western music. In earlier work, we provided evidence that consonance perception is based on neural temporal coding in the brainstem (Bones et al., 2014). Here, we show that for listeners with clinically normal hearing, aging is associated with a decline in both the perceptual distinction and the distinctiveness of the neural representations of different categories of two-note chords. Compared with younger listeners, older listeners rated consonant chords as less pleasant and dissonant chords as more pleasant. Older listeners also had less distinct neural representations of consonant and dissonant chords as measured using a Neural Consonance Index derived from the electrophysiological “frequency-following response.” The results withstood a control for the effect of age on general affect, suggesting that different mechanisms are responsible for the perceived pleasantness of musical chords and affective voices and that, for listeners with clinically normal hearing, age-related differences in consonance perception are likely to be related to differences in neural temporal coding. PMID:25740534

Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

PubMed

Ignatius, Myron S; Unal Eroglu, Arife; Malireddy, Smitha; Gallagher, Glen; Nambiar, Roopa M; Henion, Paul D

2013-01-01

The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382) mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382) mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382) mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382) defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

Auditory-nerve responses predict pitch attributes related to musical consonance-dissonance for normal and impaired hearinga

PubMed Central

Bidelman, Gavin M.; Heinz, Michael G.

2011-01-01

Human listeners prefer consonant over dissonant musical intervals and the perceived contrast between these classes is reduced with cochlear hearing loss. Population-level activity of normal and impaired model auditory-nerve (AN) fibers was examined to determine (1) if peripheral auditory neurons exhibit correlates of consonance and dissonance and (2) if the reduced perceptual difference between these qualities observed for hearing-impaired listeners can be explained by impaired AN responses. In addition, acoustical correlates of consonance-dissonance were also explored including periodicity and roughness. Among the chromatic pitch combinations of music, consonant intervals∕chords yielded more robust neural pitch-salience magnitudes (determined by harmonicity∕periodicity) than dissonant intervals∕chords. In addition, AN pitch-salience magnitudes correctly predicted the ordering of hierarchical pitch and chordal sonorities described by Western music theory. Cochlear hearing impairment compressed pitch salience estimates between consonant and dissonant pitch relationships. The reduction in contrast of neural responses following cochlear hearing loss may explain the inability of hearing-impaired listeners to distinguish musical qualia as clearly as normal-hearing individuals. Of the neural and acoustic correlates explored, AN pitch salience was the best predictor of behavioral data. Results ultimately show that basic pitch relationships governing music are already present in initial stages of neural processing at the AN level. PMID:21895089

What Are Neural Tube Defects?

MedlinePlus

... are born with spina bifida will have normal intelligence, but some will have learning or intellectual disabilities . ... effects, some children with this condition have normal intelligence. 6 Iniencephaly Iniencephaly(pronounced in-ee-ehn-SEF- ...

Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

PubMed

Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

2012-01-01

Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and represent important end-points for analysis in studies of therapeutic strategies to protect patients from neural dysfunction.

Automatic segmentation method of pelvic floor levator hiatus in ultrasound using a self-normalizing neural network

PubMed Central

Dietz, Hans Peter; D’hooge, Jan; Barratt, Dean; Deprest, Jan

2018-01-01

Abstract. Segmentation of the levator hiatus in ultrasound allows the extraction of biometrics, which are of importance for pelvic floor disorder assessment. We present a fully automatic method using a convolutional neural network (CNN) to outline the levator hiatus in a two-dimensional image extracted from a three-dimensional ultrasound volume. In particular, our method uses a recently developed scaled exponential linear unit (SELU) as a nonlinear self-normalizing activation function, which for the first time has been applied in medical imaging with CNN. SELU has important advantages such as being parameter-free and mini-batch independent, which may help to overcome memory constraints during training. A dataset with 91 images from 35 patients during Valsalva, contraction, and rest, all labeled by three operators, is used for training and evaluation in a leave-one-patient-out cross validation. Results show a median Dice similarity coefficient of 0.90 with an interquartile range of 0.08, with equivalent performance to the three operators (with a Williams’ index of 1.03), and outperforming a U-Net architecture without the need for batch normalization. We conclude that the proposed fully automatic method achieved equivalent accuracy in segmenting the pelvic floor levator hiatus compared to a previous semiautomatic approach. PMID:29340289

Automatic segmentation method of pelvic floor levator hiatus in ultrasound using a self-normalizing neural network.

PubMed

Bonmati, Ester; Hu, Yipeng; Sindhwani, Nikhil; Dietz, Hans Peter; D'hooge, Jan; Barratt, Dean; Deprest, Jan; Vercauteren, Tom

2018-04-01

Segmentation of the levator hiatus in ultrasound allows the extraction of biometrics, which are of importance for pelvic floor disorder assessment. We present a fully automatic method using a convolutional neural network (CNN) to outline the levator hiatus in a two-dimensional image extracted from a three-dimensional ultrasound volume. In particular, our method uses a recently developed scaled exponential linear unit (SELU) as a nonlinear self-normalizing activation function, which for the first time has been applied in medical imaging with CNN. SELU has important advantages such as being parameter-free and mini-batch independent, which may help to overcome memory constraints during training. A dataset with 91 images from 35 patients during Valsalva, contraction, and rest, all labeled by three operators, is used for training and evaluation in a leave-one-patient-out cross validation. Results show a median Dice similarity coefficient of 0.90 with an interquartile range of 0.08, with equivalent performance to the three operators (with a Williams' index of 1.03), and outperforming a U-Net architecture without the need for batch normalization. We conclude that the proposed fully automatic method achieved equivalent accuracy in segmenting the pelvic floor levator hiatus compared to a previous semiautomatic approach.

Predict human body indentation lying on a spring mattress using a neural network approach.

PubMed

Zhong, Shilu; Shen, Liming; Zhou, Lijuan; Guan, Zhongwei

2014-08-01

This article presents a method to predict and assess the interaction between a human body and a spring mattress. A three-layer artificial neural network model was developed to simulate and predict an indentation curve of human spine, characterized with the depth of lumbar lordosis and four inclination angles: cervicothoracic, thoracolumbar, lumbosacral and the back-hip (β). By comparing the spinal indentation curves described by the optimal evaluation parameters (depth of lumbar lordosis, cervicothoracic, thoracolumbar and lumbosacral), a better design of five-zone spring mattresses was obtained for individuals to have an effective support to the main part of the body. Using such approach, an operating process was further introduced, in which appropriate stiffness proportions were proposed to design mattress for the normal body types of Chinese young women. Finally, case studies were undertaken, which show that the method developed is feasible and practical. © IMechE 2014.

Movement maintains forebrain neurogenesis via peripheral neural feedback in larval zebrafish

PubMed Central

Hall, Zachary Jonas

2018-01-01

The postembryonic brain exhibits experience-dependent development, in which sensory experience guides normal brain growth. This neuroplasticity is thought to occur primarily through structural and functional changes in pre-existing neurons. Whether neurogenesis also mediates the effects of experience on brain growth is unclear. Here, we characterized the importance of motor experience on postembryonic neurogenesis in larval zebrafish. We found that movement maintains an expanded pool of forebrain neural precursors by promoting progenitor self-renewal over the production of neurons. Physical cues associated with swimming (bodily movement) increase neurogenesis and these cues appear to be conveyed by dorsal root ganglia (DRG) in the zebrafish body: DRG-deficient larvae exhibit attenuated neurogenic responses to movement and targeted photoactivation of DRG in immobilized larvae expands the pallial pool of proliferative cells. Our results demonstrate the importance of movement in neurogenic brain growth and reveal a fundamental sensorimotor association that may couple early motor and brain development. PMID:29528285

The intracellular responses of frog eggs to novel orientations to gravity

NASA Technical Reports Server (NTRS)

Radice, G. P.; Neff, A. W.; Malacinski, G. M.

1982-01-01

It is found that multiple short doses of ultraviolet light are as effective as a single large dose in producing neural defects. In addition, 180 deg rotation (inversion) of irradiated eggs reduces the ultraviolet effect. Since yolk platelets may be the gravity sensing mechanism, their size, density, and distribution in normal and inverted eggs are investigated. Large platelets are denser and for the most part are in a distinct zone in the vegetal hemisphere, whereas small platelets are less dense and occur in the animal hemisphere. When inverted, the large platelets flow into the animal hemisphere as a coherent mass and partially displace the small platelets. Inversion is thought to rearrange cytoplasmic components necessary for later neural development into an appropriate configuration.

Grain-Boundary Resistance in Copper Interconnects: From an Atomistic Model to a Neural Network

NASA Astrophysics Data System (ADS)

Valencia, Daniel; Wilson, Evan; Jiang, Zhengping; Valencia-Zapata, Gustavo A.; Wang, Kuang-Chung; Klimeck, Gerhard; Povolotskyi, Michael

2018-04-01

Orientation effects on the specific resistance of copper grain boundaries are studied systematically with two different atomistic tight-binding methods. A methodology is developed to model the specific resistance of grain boundaries in the ballistic limit using the embedded atom model, tight- binding methods, and nonequilibrium Green's functions. The methodology is validated against first-principles calculations for thin films with a single coincident grain boundary, with 6.4% deviation in the specific resistance. A statistical ensemble of 600 large, random structures with grains is studied. For structures with three grains, it is found that the distribution of specific resistances is close to normal. Finally, a compact model for grain-boundary-specific resistance is constructed based on a neural network.

Coding of sounds in the auditory system and its relevance to signal processing and coding in cochlear implants.

PubMed

Moore, Brian C J

2003-03-01

To review how the properties of sounds are "coded" in the normal auditory system and to discuss the extent to which cochlear implants can and do represent these codes. Data are taken from published studies of the response of the cochlea and auditory nerve to simple and complex stimuli, in both the normal and the electrically stimulated ear. REVIEW CONTENT: The review describes: 1) the coding in the normal auditory system of overall level (which partly determines perceived loudness), spectral shape (which partly determines perceived timbre and the identity of speech sounds), periodicity (which partly determines pitch), and sound location; 2) the role of the active mechanism in the cochlea, and particularly the fast-acting compression associated with that mechanism; 3) the neural response patterns evoked by cochlear implants; and 4) how the response patterns evoked by implants differ from those observed in the normal auditory system in response to sound. A series of specific issues is then discussed, including: 1) how to compensate for the loss of cochlear compression; 2) the effective number of independent channels in a normal ear and in cochlear implantees; 3) the importance of independence of responses across neurons; 4) the stochastic nature of normal neural responses; 5) the possible role of across-channel coincidence detection; and 6) potential benefits of binaural implantation. Current cochlear implants do not adequately reproduce several aspects of the neural coding of sound in the normal auditory system. Improved electrode arrays and coding systems may lead to improved coding and, it is hoped, to better performance.

Analysis of NUAK1 and NUAK2 expression during early chick development reveals specific patterns in the developing head.

PubMed

Bekri, Abdelhamid; Billaud, Marc; Thélu, Jacques

2014-01-01

Several human diseases are associated with the NUAK1 and NUAK2 genes. These genes encode kinases, members of the AMPK-related kinases (ARK) gene family. Both NUAK1 and NUAK2 are known targets of the serine threonine kinase LKB1, a tumor suppressor involved in regulating cell polarity. While much is known about their functions in disease, their expression pattern in normal development has not been extensively studied. Here, we present the expression patterns for NUAK1 and NUAK2 in the chick during early-stage embryogenesis, until day 3 (Hamburger and Hamilton stage HH20). Several embryonic structures, in particular the nascent head, showed distinct expression levels. NUAK1 expression was first detected at stage HH6 in the rostral neural folds. It was then expressed (HH7-11) throughout the encephalalon, predominantly in the telencephalon and mesencephalon. NUAK1 expression was also detected in the splanchnic endoderm area at HH8-10, and in the vitellin vein derived from this area, but not in the heart. NUAK2 expression was first detected at stage HH6 in the neural folds. It was then found throughout the encephalon at stage HH20. Particular attention was paid in this study to the dorsal ectoderm at stages HH7 and HH8, where a local deficit or accumulation of NUAK2 mRNA were found to correlate with the direction of curvature of the neural plate. This is the first description of NUAK1 and NUAK2 expression patterns in the chick during early development; it reveals non-identical expression profiles for both genes in neural development.

Local and long-range endogenous resting potential gradients antagonistically regulate apoptosis and proliferation in the embryonic CNS.

PubMed

Pai, Vaibhav P; Lemire, Joan M; Chen, Ying; Lin, Gufa; Levin, Michael

2015-01-01

Bioelectric signals, particularly transmembrane voltage potentials (Vmem), play an important role in large-scale patterning during embryonic development. Endogenous bioelectric gradients across tissues function as instructive factors during eye, brain, and other morphogenetic processes. An important and still poorly-understood aspect is the control of cell behaviors by the voltage states of distant cell groups. Here, experimental alteration of endogenous Vmem was induced in Xenopus laevis embryos by misexpression of well-characterized ion channel mRNAs, a strategy often used to identify functional roles of Vmem gradients during embryonic development and regeneration. Immunofluorescence analysis (for activated caspase 3 and phosphor-histone H3P) on embryonic sections was used to characterize apoptosis and proliferation. Disrupting local bioelectric signals (within the developing neural tube region) increased caspase 3 and decreased H3P in the brain, resulting in brain mispatterning. Disrupting remote (ventral, non-neural region) bioelectric signals decreased caspase 3 and highly increased H3P within the brain, with normal brain patterning. Disrupting both the local and distant bioelectric signals produced antagonistic effects on caspase 3 and H3P. Thus, two components of bioelectric signals regulate apoptosis-proliferation balance within the developing brain and spinal cord: local (developing neural tube region) and distant (ventral non-neural region). Together, the local and long-range bioelectric signals create a binary control system capable of fine-tuning apoptosis and proliferation with the brain and spinal cord to achieve correct pattern and size control. Our data suggest a roadmap for utilizing bioelectric state as a diagnostic modality and convenient intervention parameter for birth defects and degenerative disease states of the CNS.

Altered behavior and neural activity in conspecific cagemates co-housed with mouse models of brain disorders.

PubMed

Yang, Hyunwoo; Jung, Seungmoon; Seo, Jinsoo; Khalid, Arshi; Yoo, Jung-Seok; Park, Jihyun; Kim, Soyun; Moon, Jangsup; Lee, Soon-Tae; Jung, Keun-Hwa; Chu, Kon; Lee, Sang Kun; Jeon, Daejong

2016-09-01

The psychosocial environment is one of the major contributors of social stress. Family members or caregivers who consistently communicate with individuals with brain disorders are considered at risk for physical and mental health deterioration, possibly leading to mental disorders. However, the underlying neural mechanisms of this phenomenon remain poorly understood. To address this, we developed a social stress paradigm in which a mouse model of epilepsy or depression was housed long-term (>4weeks) with normal conspecifics. We characterized the behavioral phenotypes and electrophysiologically investigated the neural activity of conspecific cagemate mice. The cagemates exhibited deficits in behavioral tasks assessing anxiety, locomotion, learning/memory, and depression-like behavior. Furthermore, they showed severe social impairment in social behavioral tasks involving social interaction or aggression. Strikingly, behavioral dysfunction remained in the cagemates 4weeks following co-housing cessation with the mouse models. In an electrophysiological study, the cagemates showed an increased number of spikes in medial prefrontal cortex (mPFC) neurons. Our results demonstrate that conspecifics co-housed with mouse models of brain disorders develop chronic behavioral dysfunctions, and suggest a possible association between abnormal mPFC neural activity and their behavioral pathogenesis. These findings contribute to the understanding of the psychosocial and psychiatric symptoms frequently present in families or caregivers of patients with brain disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Performance of wavelet analysis and neural networks for pathological voices identification

NASA Astrophysics Data System (ADS)

Salhi, Lotfi; Talbi, Mourad; Abid, Sabeur; Cherif, Adnane

2011-09-01

Within the medical environment, diverse techniques exist to assess the state of the voice of the patient. The inspection technique is inconvenient for a number of reasons, such as its high cost, the duration of the inspection, and above all, the fact that it is an invasive technique. This study focuses on a robust, rapid and accurate system for automatic identification of pathological voices. This system employs non-invasive, non-expensive and fully automated method based on hybrid approach: wavelet transform analysis and neural network classifier. First, we present the results obtained in our previous study while using classic feature parameters. These results allow visual identification of pathological voices. Second, quantified parameters drifting from the wavelet analysis are proposed to characterise the speech sample. On the other hand, a system of multilayer neural networks (MNNs) has been developed which carries out the automatic detection of pathological voices. The developed method was evaluated using voice database composed of recorded voice samples (continuous speech) from normophonic or dysphonic speakers. The dysphonic speakers were patients of a National Hospital 'RABTA' of Tunis Tunisia and a University Hospital in Brussels, Belgium. Experimental results indicate a success rate ranging between 75% and 98.61% for discrimination of normal and pathological voices using the proposed parameters and neural network classifier. We also compared the average classification rate based on the MNN, Gaussian mixture model and support vector machines.

A Systematic Review for Functional Neuroimaging Studies of Cognitive Reserve Across the Cognitive Aging Spectrum.

PubMed

Anthony, Mia; Lin, Feng

2017-12-13

Cognitive reserve has been proposed to explain the discrepancy between clinical symptoms and the effects of aging or Alzheimer's pathology. Functional magnetic resonance imaging (fMRI) may help elucidate how neural reserve and compensation delay cognitive decline and identify brain regions associated with cognitive reserve. This systematic review evaluated neural correlates of cognitive reserve via fMRI (resting-state and task-related) studies across the cognitive aging spectrum (i.e., normal cognition, mild cognitive impairment, and Alzheimer's disease). This review examined published articles up to March 2017. There were 13 cross-sectional observational studies that met the inclusion criteria, including relevance to cognitive reserve, subjects 60 years or older with normal cognition, mild cognitive impairment, and/or Alzheimer's disease, at least one quantitative measure of cognitive reserve, and fMRI as the imaging modality. Quality assessment of included studies was conducted using the Newcastle-Ottawa Scale adapted for cross-sectional studies. Across the cognitive aging spectrum, medial temporal regions and an anterior or posterior cingulate cortex-seeded default mode network were associated with neural reserve. Frontal regions and the dorsal attentional network were related to neural compensation. Compared to neural reserve, neural compensation was more common in mild cognitive impairment and Alzheimer's disease. Neural reserve and compensation both support cognitive reserve, with compensation more common in later stages of the cognitive aging spectrum. Longitudinal and intervention studies are needed to investigate changes between neural reserve and compensation during the transition between clinical stages, and to explore the causal relationship between cognitive reserve and potential neural substrates. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Dynamic divisive normalization predicts time-varying value coding in decision-related circuits.

PubMed

Louie, Kenway; LoFaro, Thomas; Webb, Ryan; Glimcher, Paul W

2014-11-26

Normalization is a widespread neural computation, mediating divisive gain control in sensory processing and implementing a context-dependent value code in decision-related frontal and parietal cortices. Although decision-making is a dynamic process with complex temporal characteristics, most models of normalization are time-independent and little is known about the dynamic interaction of normalization and choice. Here, we show that a simple differential equation model of normalization explains the characteristic phasic-sustained pattern of cortical decision activity and predicts specific normalization dynamics: value coding during initial transients, time-varying value modulation, and delayed onset of contextual information. Empirically, we observe these predicted dynamics in saccade-related neurons in monkey lateral intraparietal cortex. Furthermore, such models naturally incorporate a time-weighted average of past activity, implementing an intrinsic reference-dependence in value coding. These results suggest that a single network mechanism can explain both transient and sustained decision activity, emphasizing the importance of a dynamic view of normalization in neural coding. Copyright © 2014 the authors 0270-6474/14/3416046-12$15.00/0.

Application of an artificial neural network and morphing techniques in the redesign of dysplastic trochlea.

PubMed

Cho, Kyung Jin; Müller, Jacobus H; Erasmus, Pieter J; DeJour, David; Scheffer, Cornie

2014-01-01

Segmentation and computer assisted design tools have the potential to test the validity of simulated surgical procedures, e.g., trochleoplasty. A repeatable measurement method for three dimensional femur models that enables quantification of knee parameters of the distal femur is presented. Fifteen healthy knees are analysed using the method to provide a training set for an artificial neural network. The aim is to use this artificial neural network for the prediction of parameter values that describe the shape of a normal trochlear groove geometry. This is achieved by feeding the artificial neural network with the unaffected parameters of a dysplastic knee. Four dysplastic knees (Type A through D) are virtually redesigned by way of morphing the groove geometries based on the suggested shape from the artificial neural network. Each of the four resulting shapes is analysed and compared to its initial dysplastic shape in terms of three anteroposterior dimensions: lateral, central and medial. For the four knees the trochlear depth is increased, the ventral trochlear prominence reduced and the sulcus angle corrected to within published normal ranges. The results show a lateral facet elevation inadequate, with a sulcus deepening or a depression trochleoplasty more beneficial to correct trochlear dysplasia.

Neural preservation underlies speech improvement from auditory deprivation in young cochlear implant recipients.

PubMed

Feng, Gangyi; Ingvalson, Erin M; Grieco-Calub, Tina M; Roberts, Megan Y; Ryan, Maura E; Birmingham, Patrick; Burrowes, Delilah; Young, Nancy M; Wong, Patrick C M

2018-01-30

Although cochlear implantation enables some children to attain age-appropriate speech and language development, communicative delays persist in others, and outcomes are quite variable and difficult to predict, even for children implanted early in life. To understand the neurobiological basis of this variability, we used presurgical neural morphological data obtained from MRI of individual pediatric cochlear implant (CI) candidates implanted younger than 3.5 years to predict variability of their speech-perception improvement after surgery. We first compared neuroanatomical density and spatial pattern similarity of CI candidates to that of age-matched children with normal hearing, which allowed us to detail neuroanatomical networks that were either affected or unaffected by auditory deprivation. This information enables us to build machine-learning models to predict the individual children's speech development following CI. We found that regions of the brain that were unaffected by auditory deprivation, in particular the auditory association and cognitive brain regions, produced the highest accuracy, specificity, and sensitivity in patient classification and the most precise prediction results. These findings suggest that brain areas unaffected by auditory deprivation are critical to developing closer to typical speech outcomes. Moreover, the findings suggest that determination of the type of neural reorganization caused by auditory deprivation before implantation is valuable for predicting post-CI language outcomes for young children.

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate

PubMed Central

Falcone, Mary; Cao, Wen; Bernardo, Leah; Tyndale, Rachel F; Loughead, James; Lerman, Caryn

2017-01-01

Background Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (NMR, 3′-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance, and a well validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers. Methods Sixty-nine treatment-seeking smokers (30 slow, 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once following 24 hours of smoking abstinence. Results In whole brain analysis, normal (compared to slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were even more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke. Conclusion Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy. PMID:26805583

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate.

PubMed

Falcone, Mary; Cao, Wen; Bernardo, Leah; Tyndale, Rachel F; Loughead, James; Lerman, Caryn

2016-08-01

Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (3'-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance and a well-validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers. Treatment-seeking smokers (N = 69; 30 slow metabolizers and 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once after 24 hours of smoking abstinence. In whole-brain analysis, normal (compared with slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke. Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Fractional Snow Cover Mapping by Artificial Neural Networks and Support Vector Machines

NASA Astrophysics Data System (ADS)

Çiftçi, B. B.; Kuter, S.; Akyürek, Z.; Weber, G.-W.

2017-11-01

Snow is an important land cover whose distribution over space and time plays a significant role in various environmental processes. Hence, snow cover mapping with high accuracy is necessary to have a real understanding for present and future climate, water cycle, and ecological changes. This study aims to investigate and compare the design and use of artificial neural networks (ANNs) and support vector machines (SVMs) algorithms for fractional snow cover (FSC) mapping from satellite data. ANN and SVM models with different model building settings are trained by using Moderate Resolution Imaging Spectroradiometer surface reflectance values of bands 1-7, normalized difference snow index and normalized difference vegetation index as predictor variables. Reference FSC maps are generated from higher spatial resolution Landsat ETM+ binary snow cover maps. Results on the independent test data set indicate that the developed ANN model with hyperbolic tangent transfer function in the output layer and the SVM model with radial basis function kernel produce high FSC mapping accuracies with the corresponding values of R = 0.93 and R = 0.92, respectively.

[Injuries of the cervical spine in patients with ankylosing spondylitis].

PubMed

Vaverka, M; Hrabálek, L

2001-01-01

A brittle and rigid, osteoporotic and injury prone "bamboo" spine which develops as a result of transformation of the normal spine in the final stage of Bekhterev's disease contains normal neural elements. Unstable fractures occur frequently even after a minimal injury and the morbidity and mortality is significantly higher than in the group of routine injuries of the cervical, spine, in particular as a result of pulmonary complications. Diagnosis of the fracture based on simple X-ray pictures is difficult, CT examination is essential. The authors present an account on their experience with three patients. They draw attention to problems of skeletal traction when the spinal axis is altered by disease and to risks associated with semiconservative treatment. The authors therefore recommend traction with a minimal load and with subsequent early decompression and stabilization by a combined anterior and posterior approach in a single session. By this approach secondary affection of neural structures in unstable fractures can be prevented, and early rehabilitation with verticalization without restriction of respiratory excursions by an orthesis then significantly reduces the risk of pulmonary complications.

Program Aids Analysis And Optimization Of Design

NASA Technical Reports Server (NTRS)

Rogers, James L., Jr.; Lamarsh, William J., II

1994-01-01

NETS/ PROSSS (NETS Coupled With Programming System for Structural Synthesis) computer program developed to provide system for combining NETS (MSC-21588), neural-network application program and CONMIN (Constrained Function Minimization, ARC-10836), optimization program. Enables user to reach nearly optimal design. Design then used as starting point in normal optimization process, possibly enabling user to converge to optimal solution in significantly fewer iterations. NEWT/PROSSS written in C language and FORTRAN 77.

F-15 837 IFCS Intelligent Flight Control System Project

NASA Technical Reports Server (NTRS)

Bosworth, John T.

2007-01-01

This viewgraph presentation reviews the use of Intelligent Flight Control System (IFCS) for the F-15. The goals of the project are: (1) Demonstrate Revolutionary Control Approaches that can Efficiently Optimize Aircraft Performance in both Normal and Failure Conditions (2) Advance Neural Network-Based Flight Control Technology for New Aerospace Systems Designs. The motivation for the development are to reduce the chance and skill required for survival.

Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways

NASA Astrophysics Data System (ADS)

Chung, Won-Suk; Clarke, Laura E.; Wang, Gordon X.; Stafford, Benjamin K.; Sher, Alexander; Chakraborty, Chandrani; Joung, Julia; Foo, Lynette C.; Thompson, Andrew; Chen, Chinfei; Smith, Stephen J.; Barres, Ben A.

2013-12-01

To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodelling. Recently, microglial cells have been shown to be responsible for a portion of synaptic pruning, but the remaining mechanisms remain unknown. Here we report a new role for astrocytes in actively engulfing central nervous system synapses. This process helps to mediate synapse elimination, requires the MEGF10 and MERTK phagocytic pathways, and is strongly dependent on neuronal activity. Developing mice deficient in both astrocyte pathways fail to refine their retinogeniculate connections normally and retain excess functional synapses. Finally, we show that in the adult mouse brain, astrocytes continuously engulf both excitatory and inhibitory synapses. These studies reveal a novel role for astrocytes in mediating synapse elimination in the developing and adult brain, identify MEGF10 and MERTK as critical proteins in the synapse remodelling underlying neural circuit refinement, and have important implications for understanding learning and memory as well as neurological disease processes.

The N-Methyl-D-Aspartate Receptor in Heart Development: A Gene Knockdown Model Using siRNA

PubMed Central

Lie, Octavian V.; Bennett, Gregory D.; Rosenquist, Thomas H

2009-01-01

Antagonists of the N-methyl-D-aspartate receptor (NMDAR) may disrupt the development of the cardiac neural crest (CNC) and contribute to conotruncal heart defects. To test this interaction, a loss-of-function model was generated using small interfering RNAs (siRNA) directed against the critical NR1-subunit of this receptor in avian embryos. The coding sequence of the chicken NR1-gene and predicted protein sequences were characterized and found to be homologous with other vertebrate species. Analysis of its spatiotemporal expression demonstrated its expression within the neural tube at pre-migratory CNC sites. siRNA targeted to the NR1-mRNA in pre-migratory CNC lead to a significant decrease in NR1 protein expression. However, embryo survival and heart development were not adversely affected. These results indicate that the CNC may function normally in the absence of functional NMDAR, and that NMDAR antagonists may have a complex impact upon the CNC that transcends impairment of a single receptor type. PMID:19737608

The epigenetic switches for neural development and psychiatric disorders.

PubMed

Lv, Jingwen; Xin, Yongjuan; Zhou, Wenhao; Qiu, Zilong

2013-07-20

The most remarkable feature of the nervous system is that the development and functions of the brain are largely reshaped by postnatal experiences, in joint with genetic landscapes. The nature vs. nurture argument reminds us that both genetic and epigenetic information is indispensable for the normal function of the brain. The epigenetic regulatory mechanisms in the central nervous system have been revealed over last a decade. Moreover, the mutations of epigenetic modulator genes have been shown to be implicated in neuropsychiatric disorders, such as autism spectrum disorders. The epigenetic study has initiated in the neuroscience field for a relative short period of time. In this review, we will summarize recent discoveries about epigenetic regulation on neural development, synaptic plasticity, learning and memory, as well as neuropsychiatric disorders. Although the comprehensive view of how epigenetic regulation contributes to the function of the brain is still not completed, the notion that brain, the most complicated organ of organisms, is profoundly shaped by epigenetic switches is widely accepted. Copyright © 2013. Published by Elsevier Ltd.

Blood pressure long term regulation: A neural network model of the set point development

PubMed Central

2011-01-01

Background The notion of the nucleus tractus solitarius (NTS) as a comparator evaluating the error signal between its rostral neural structures (RNS) and the cardiovascular receptor afferents into it has been recently presented. From this perspective, stress can cause hypertension via set point changes, so offering an answer to an old question. Even though the local blood flow to tissues is influenced by circulating vasoactive hormones and also by local factors, there is yet significant sympathetic control. It is well established that the state of maturation of sympathetic innervation of blood vessels at birth varies across animal species and it takes place mostly during the postnatal period. During ontogeny, chemoreceptors are functional; they discharge when the partial pressures of oxygen and carbon dioxide in the arterial blood are not normal. Methods The model is a simple biological plausible adaptative neural network to simulate the development of the sympathetic nervous control. It is hypothesized that during ontogeny, from the RNS afferents to the NTS, the optimal level of each sympathetic efferent discharge is learned through the chemoreceptors' feedback. Its mean discharge leads to normal oxygen and carbon dioxide levels in each tissue. Thus, the sympathetic efferent discharge sets at the optimal level if, despite maximal drift, the local blood flow is compensated for by autoregulation. Such optimal level produces minimum chemoreceptor output, which must be maintained by the nervous system. Since blood flow is controlled by arterial blood pressure, the long-term mean level is stabilized to regulate oxygen and carbon dioxide levels. After development, the cardiopulmonary reflexes play an important role in controlling efferent sympathetic nerve activity to the kidneys and modulating sodium and water excretion. Results Starting from fixed RNS afferents to the NTS and random synaptic weight values, the sympathetic efferents converged to the optimal values. When learning was completed, the output from the chemoreceptors became zero because the sympathetic efferents led to normal partial pressures of oxygen and carbon dioxide. Conclusions We introduce here a simple simulating computational theory to study, from a neurophysiologic point of view, the sympathetic development of cardiovascular regulation due to feedback signals sent off by cardiovascular receptors. The model simulates, too, how the NTS, as emergent property, acts as a comparator and how its rostral afferents behave as set point. PMID:21693057

Meninges: from protective membrane to stem cell niche.

PubMed

Decimo, Ilaria; Fumagalli, Guido; Berton, Valeria; Krampera, Mauro; Bifari, Francesco

2012-01-01

Meninges are a three tissue membrane primarily known as coverings of the brain. More in depth studies on meningeal function and ultrastructure have recently changed the view of meninges as a merely protective membrane. Accurate evaluation of the anatomical distribution in the CNS reveals that meninges largely penetrate inside the neural tissue. Meninges enter the CNS by projecting between structures, in the stroma of choroid plexus and form the perivascular space (Virchow-Robin) of every parenchymal vessel. Thus, meninges may modulate most of the physiological and pathological events of the CNS throughout the life. Meninges are present since the very early embryonic stages of cortical development and appear to be necessary for normal corticogenesis and brain structures formation. In adulthood meninges contribute to neural tissue homeostasis by secreting several trophic factors including FGF2 and SDF-1. Recently, for the first time, we have identified the presence of a stem cell population with neural differentiation potential in meninges. In addition, we and other groups have further described the presence in meninges of injury responsive neural precursors. In this review we will give a comprehensive view of meninges and their multiple roles in the context of a functional network with the neural tissue. We will highlight the current literature on the developmental feature of meninges and their role in cortical development. Moreover, we will elucidate the anatomical distribution of the meninges and their trophic properties in adult CNS. Finally, we will emphasize recent evidences suggesting the potential role of meninges as stem cell niche harbouring endogenous precursors that can be activated by injury and are able to contribute to CNS parenchymal reaction.

Prototype to product—developing a commercially viable neural prosthesis

NASA Astrophysics Data System (ADS)

Seligman, Peter

2009-12-01

The Cochlear implant or 'Bionic ear' is a device that enables people who do not get sufficient benefit from a hearing aid to communicate with the hearing world. The Cochlear implant is not an amplifier, but a device that electrically stimulates the auditory nerve in a way that crudely mimics normal hearing, thus providing a hearing percept. Many recipients are able to understand running speech without the help of lipreading. Cochlear implants have reached a stage of maturity where there are now 170 000 recipients implanted worldwide. The commercial development of these devices has occurred over the last 30 years. This development has been multidisciplinary, including audiologists, engineers, both mechanical and electrical, histologists, materials scientists, physiologists, surgeons and speech pathologists. This paper will trace the development of the device we have today, from the engineering perspective. The special challenges of designing an active device that will work in the human body for a lifetime will be outlined. These challenges include biocompatibility, extreme reliability, safety, patient fitting and surgical issues. It is emphasized that the successful development of a neural prosthesis requires the partnership of academia and industry.

Prototype to product-developing a commercially viable neural prosthesis.

PubMed

Seligman, Peter

2009-12-01

The Cochlear implant or 'Bionic ear' is a device that enables people who do not get sufficient benefit from a hearing aid to communicate with the hearing world. The Cochlear implant is not an amplifier, but a device that electrically stimulates the auditory nerve in a way that crudely mimics normal hearing, thus providing a hearing percept. Many recipients are able to understand running speech without the help of lipreading. Cochlear implants have reached a stage of maturity where there are now 170 000 recipients implanted worldwide. The commercial development of these devices has occurred over the last 30 years. This development has been multidisciplinary, including audiologists, engineers, both mechanical and electrical, histologists, materials scientists, physiologists, surgeons and speech pathologists. This paper will trace the development of the device we have today, from the engineering perspective. The special challenges of designing an active device that will work in the human body for a lifetime will be outlined. These challenges include biocompatibility, extreme reliability, safety, patient fitting and surgical issues. It is emphasized that the successful development of a neural prosthesis requires the partnership of academia and industry.

Establishment and Characterization of Immortalized Minipig Neural Stem Cell Line

PubMed Central

Choi, Sung S.; Yoon, Seung-Bin; Lee, Sang-Rae; Kim, Sun-Uk; Cha, Young Joo; Lee, Daniel; Kim, Seung U.; Chang, Kyu-Tae; Lee, Hong J.

2017-01-01

Despite the increasing importance of minipigs in biomedical research, there has been relatively little research concerning minipig-derived adult stem cells as a promising research tool that could be used to develop stem cell-based therapies. We first generated immortalized neural stem cells (iNSCs) from primary minipig olfactory bulb cells (pmpOBCs) and defined the characteristics of the cell line. Primary neural cells were prepared from minipig neonate olfactory bulbs and immortalized by infection with retrovirus carrying the v-myc gene. The minipig iNSCs (mpiNSCs) had normal karyotypes and expressed NSC-specific markers, including nestin, vimentin, Musashi1, and SOX2, suggesting a similarity to human NSCs. On the basis of the global gene expression profiles from the microarray analysis, neurogenesis-associated transcript levels were predominantly altered in mpiNSCs compared with pmpOBCs. These findings increase our understanding of minipig stem cells and contribute to the utility of mpiNSCs as resources for immortalized stem cell experiments. PMID:27524466

On-line Tool Wear Detection on DCMT070204 Carbide Tool Tip Based on Noise Cutting Audio Signal using Artificial Neural Network

NASA Astrophysics Data System (ADS)

Prasetyo, T.; Amar, S.; Arendra, A.; Zam Zami, M. K.

2018-01-01

This study develops an on-line detection system to predict the wear of DCMT070204 tool tip during the cutting process of the workpiece. The machine used in this research is CNC ProTurn 9000 to cut ST42 steel cylinder. The audio signal has been captured using the microphone placed in the tool post and recorded in Matlab. The signal is recorded at the sampling rate of 44.1 kHz, and the sampling size of 1024. The recorded signal is 110 data derived from the audio signal while cutting using a normal chisel and a worn chisel. And then perform signal feature extraction in the frequency domain using Fast Fourier Transform. Feature selection is done based on correlation analysis. And tool wear classification was performed using artificial neural networks with 33 input features selected. This artificial neural network is trained with back propagation method. Classification performance testing yields an accuracy of 74%.

Statistical Modeling and Prediction for Tourism Economy Using Dendritic Neural Network

PubMed Central

Yu, Ying; Wang, Yirui; Tang, Zheng

2017-01-01

With the impact of global internationalization, tourism economy has also been a rapid development. The increasing interest aroused by more advanced forecasting methods leads us to innovate forecasting methods. In this paper, the seasonal trend autoregressive integrated moving averages with dendritic neural network model (SA-D model) is proposed to perform the tourism demand forecasting. First, we use the seasonal trend autoregressive integrated moving averages model (SARIMA model) to exclude the long-term linear trend and then train the residual data by the dendritic neural network model and make a short-term prediction. As the result showed in this paper, the SA-D model can achieve considerably better predictive performances. In order to demonstrate the effectiveness of the SA-D model, we also use the data that other authors used in the other models and compare the results. It also proved that the SA-D model achieved good predictive performances in terms of the normalized mean square error, absolute percentage of error, and correlation coefficient. PMID:28246527

Statistical Modeling and Prediction for Tourism Economy Using Dendritic Neural Network.

PubMed

Yu, Ying; Wang, Yirui; Gao, Shangce; Tang, Zheng

2017-01-01

With the impact of global internationalization, tourism economy has also been a rapid development. The increasing interest aroused by more advanced forecasting methods leads us to innovate forecasting methods. In this paper, the seasonal trend autoregressive integrated moving averages with dendritic neural network model (SA-D model) is proposed to perform the tourism demand forecasting. First, we use the seasonal trend autoregressive integrated moving averages model (SARIMA model) to exclude the long-term linear trend and then train the residual data by the dendritic neural network model and make a short-term prediction. As the result showed in this paper, the SA-D model can achieve considerably better predictive performances. In order to demonstrate the effectiveness of the SA-D model, we also use the data that other authors used in the other models and compare the results. It also proved that the SA-D model achieved good predictive performances in terms of the normalized mean square error, absolute percentage of error, and correlation coefficient.

Establishment and Characterization of Immortalized Minipig Neural Stem Cell Line.

PubMed

Choi, Sung S; Yoon, Seung-Bin; Lee, Sang-Rae; Kim, Sun-Uk; Cha, Young Joo; Lee, Daniel; Kim, Seung U; Chang, Kyu-Tae; Lee, Hong J

2017-02-16

Despite the increasing importance of minipigs in biomedical research, there has been relatively little research concerning minipig-derived adult stem cells as a promising research tool that could be used to develop stem cell-based therapies. We first generated immortalized neural stem cells (iNSCs) from primary minipig olfactory bulb cells (pmpOBCs) and defined the characteristics of the cell line. Primary neural cells were prepared from minipig neonate olfactory bulbs and immortalized by infection with retrovirus carrying the v-myc gene. The minipig iNSCs (mpiNSCs) had normal karyotypes and expressed NSC-specific markers, including nestin, vimentin, Musashi1, and SOX2, suggesting a similarity to human NSCs. On the basis of the global gene expression profiles from the microarray analysis, neurogenesis-associated transcript levels were predominantly altered in mpiNSCs compared with pmpOBCs. These findings increase our understanding of minipig stem cells and contribute to the utility of mpiNSCs as resources for immortalized stem cell experiments.

Consciousness of Unification: The Mind-Matter Phallacy Bites the Dust

NASA Astrophysics Data System (ADS)

Beichler, James E.

A complete theoretical model of how consciousness arises in neural nets can be developed based on a mixed quantum/classical basis. Both mind and consciousness are multi-leveled scalar and vector electromagnetic complexity patterns, respectively, which emerge within all living organisms through the process of evolution. Like life, the mind and consciousness patterns extend throughout living organisms (bodies), but the neural nets and higher level groupings that distinguish higher levels of consciousness only exist in the brain so mind and consciousness have been traditionally associated with the brain alone. A close study of neurons and neural nets in the brain shows that the microtubules within axons are classical bio-magnetic inductors that emit and absorb electromagnetic pulses from each other. These pulses establish interference patterns that influence the quantized vector potential patterns of interstitial water molecules within the neurons as well as create the coherence within neurons and neural nets that scientists normally associate with more complex memories, thought processes and streams of thought. Memory storage and recall are guided by the microtubules and the actual memory patterns are stored as magnetic vector potential complexity patterns in the points of space at the quantum level occupied by the water molecules. This model also accounts for the plasticity of the brain and implies that mind and consciousness, like life itself, are the result of evolutionary processes. However, consciousness can evolve independent of an organism's birth genetics once it has evolved by normal bottom-up genetic processes and thus force a new type of top-down evolution on living organisms and species as a whole that can be explained by expanding the laws of thermodynamics to include orderly systems.

Probing transcription-specific outputs of β-catenin in vivo

PubMed Central

Valenta, Tomas; Gay, Max; Steiner, Sarah; Draganova, Kalina; Zemke, Martina; Hoffmans, Raymond; Cinelli, Paolo; Aguet, Michel; Sommer, Lukas; Basler, Konrad

2011-01-01

β-Catenin, apart from playing a cell-adhesive role, is a key nuclear effector of Wnt signaling. Based on activity assays in Drosophila, we generated mouse strains where the endogenous β-catenin protein is replaced by mutant forms, which retain the cell adhesion function but lack either or both of the N- and the C-terminal transcriptional outputs. The C-terminal activity is essential for mesoderm formation and proper gastrulation, whereas N-terminal outputs are required later during embryonic development. By combining the double-mutant β-catenin with a conditional null allele and a Wnt1-Cre driver, we probed the role of Wnt/β-catenin signaling in dorsal neural tube development. While loss of β-catenin protein in the neural tube results in severe cell adhesion defects, the morphology of cells and tissues expressing the double-mutant form is normal. Surprisingly, Wnt/β-catenin signaling activity only moderately regulates cell proliferation, but is crucial for maintaining neural progenitor identity and for neuronal differentiation in the dorsal spinal cord. Our model animals thus allow dissecting signaling and structural functions of β-catenin in vivo and provide the first genetic tool to generate cells and tissues that entirely and exclusively lack canonical Wnt pathway activity. PMID:22190459

Computational neuroanatomy: ontology-based representation of neural components and connectivity

PubMed Central

Rubin, Daniel L; Talos, Ion-Florin; Halle, Michael; Musen, Mark A; Kikinis, Ron

2009-01-01

Background A critical challenge in neuroscience is organizing, managing, and accessing the explosion in neuroscientific knowledge, particularly anatomic knowledge. We believe that explicit knowledge-based approaches to make neuroscientific knowledge computationally accessible will be helpful in tackling this challenge and will enable a variety of applications exploiting this knowledge, such as surgical planning. Results We developed ontology-based models of neuroanatomy to enable symbolic lookup, logical inference and mathematical modeling of neural systems. We built a prototype model of the motor system that integrates descriptive anatomic and qualitative functional neuroanatomical knowledge. In addition to modeling normal neuroanatomy, our approach provides an explicit representation of abnormal neural connectivity in disease states, such as common movement disorders. The ontology-based representation encodes both structural and functional aspects of neuroanatomy. The ontology-based models can be evaluated computationally, enabling development of automated computer reasoning applications. Conclusion Neuroanatomical knowledge can be represented in machine-accessible format using ontologies. Computational neuroanatomical approaches such as described in this work could become a key tool in translational informatics, leading to decision support applications that inform and guide surgical planning and personalized care for neurological disease in the future. PMID:19208191

Motoneuron and sensory neuron plasticity to varying neuromuscular activity levels

NASA Technical Reports Server (NTRS)

Ishihara, Akihiko; Roy, Roland R.; Ohira, Yoshinobu; Edgerton, V. Reggie

2002-01-01

The size and phenotypic properties of the neural and muscular elements of the neuromuscular unit are matched under normal conditions. When subjected to chronic decreases or increases in neuromuscular activity, however, the adaptations in these properties are much more limited in the neural compared with the muscular elements.

A computational perspective on autism

PubMed Central

Rosenberg, Ari; Patterson, Jaclyn Sky; Angelaki, Dora E.

2015-01-01

Autism is a neurodevelopmental disorder that manifests as a heterogeneous set of social, cognitive, motor, and perceptual symptoms. This system-wide pervasiveness suggests that, rather than narrowly impacting individual systems such as affection or vision, autism may broadly alter neural computation. Here, we propose that alterations in nonlinear, canonical computations occurring throughout the brain may underlie the behavioral characteristics of autism. One such computation, called divisive normalization, balances a neuron’s net excitation with inhibition reflecting the overall activity of the neuronal population. Through neural network simulations, we investigate how alterations in divisive normalization may give rise to autism symptomatology. Our findings show that a reduction in the amount of inhibition that occurs through divisive normalization can account for perceptual consequences of autism, consistent with the hypothesis of an increased ratio of neural excitation to inhibition (E/I) in the disorder. These results thus establish a bridge between an E/I imbalance and behavioral data on autism that is currently absent. Interestingly, our findings implicate the context-dependent, neuronal milieu as a key factor in autism symptomatology, with autism reflecting a less “social” neuronal population. Through a broader discussion of perceptual data, we further examine how altered divisive normalization may contribute to a wide array of the disorder’s behavioral consequences. These analyses show how a computational framework can provide insights into the neural basis of autism and facilitate the generation of falsifiable hypotheses. A computational perspective on autism may help resolve debates within the field and aid in identifying physiological pathways to target in the treatment of the disorder. PMID:26170299

Vestigial-like 3 is a novel Ets1 interacting partner and regulates trigeminal nerve formation and cranial neural crest migration.

PubMed

Simon, Emilie; Thézé, Nadine; Fédou, Sandrine; Thiébaud, Pierre; Faucheux, Corinne

2017-10-15

Drosophila Vestigial is the founding member of a protein family containing a highly conserved domain, called Tondu, which mediates their interaction with members of the TEAD family of transcription factors (Scalloped in Drosophila ). In Drosophila , the Vestigial/Scalloped complex controls wing development by regulating the expression of target genes through binding to MCAT sequences. In vertebrates, there are four Vestigial-like genes, the functions of which are still not well understood. Here, we describe the regulation and function of vestigial-like 3 (vgll3) during Xenopus early development. A combination of signals, including FGF8, Wnt8a, Hoxa2, Hoxb2 and retinoic acid, limits vgll3 expression to hindbrain rhombomere 2. We show that vgll3 regulates trigeminal placode and nerve formation and is required for normal neural crest development by affecting their migration and adhesion properties. At the molecular level, vgll3 is a potent activator of pax3 , zic1 , Wnt and FGF , which are important for brain patterning and neural crest cell formation. Vgll3 interacts in the embryo with Tead proteins but unexpectedly with Ets1, with which it is able to stimulate a MCAT driven luciferase reporter gene. Our findings highlight a critical function for vgll3 in vertebrate early development. © 2017. Published by The Company of Biologists Ltd.

Decoding the language of epigenetics during neural development is key for understanding development as well as developmental neurotoxicity.

PubMed

Yeo, Michele; Patisaul, Heather; Liedtke, Wolfgang

2013-11-01

Neural development is a delicate process that can be disrupted by pollution that exerts detrimental impact on neural signaling. This commentary highlights recent discoveries in the arena of research at the interface of environmental toxicology and developmental neuroscience relating to toxicity mechanisms of bisphenol A (BPA), a ubiquitous chemical used in manufacturing of plastics and epoxy resins that is known to bind to and interfere with estrogen receptors, estrogen-receptor-related receptors and other receptors for gonadal steroids. It was recently observed that BPA disrupts the perinatal chloride shift, a key neurodevelopmental mechanism that brings down neuronal chloride from ~100 mM to ~20 mM within weeks. The chloride shift happens in all central nervous systems of vertebrates around parturition. High neuronal chloride supports neuron precursors' migrations, low neuronal chloride is the prerequisite for inhibitory action of neurotransmitters GABA and glycine, and thus an absolute requisite for normal functioning of the mature CNS. One critical contributor to the neuronal chloride shift is the concomitant upregulation of expression of the chloride-extruding transporter molecule, KCC2. We highlight recent findings including our discovery that BPA disrupts the chloride shift in a sex-specific manner by recruiting epigenetics mechanisms. These could be relevant for childhood neuropsychiatric disorders as well as for liability to develop chronic neuropsychiatric diseases later in life.

Predicting CYP2C19 Catalytic Parameters for Enantioselective Oxidations Using Artificial Neural Networks and a Chirality Code

PubMed Central

Hartman, Jessica H.; Cothren, Steven D.; Park, Sun-Ha; Yun, Chul-Ho; Darsey, Jerry A.; Miller, Grover P.

2013-01-01

Cytochromes P450 (CYP for isoforms) play a central role in biological processes especially metabolism of chiral molecules; thus, development of computational methods to predict parameters for chiral reactions is important for advancing this field. In this study, we identified the most optimal artificial neural networks using conformation-independent chirality codes to predict CYP2C19 catalytic parameters for enantioselective reactions. Optimization of the neural networks required identifying the most suitable representation of structure among a diverse array of training substrates, normalizing distribution of the corresponding catalytic parameters (kcat, Km, and kcat/Km), and determining the best topology for networks to make predictions. Among different structural descriptors, the use of partial atomic charges according to the CHelpG scheme and inclusion of hydrogens yielded the most optimal artificial neural networks. Their training also required resolution of poorly distributed output catalytic parameters using a Box-Cox transformation. End point leave-one-out cross correlations of the best neural networks revealed that predictions for individual catalytic parameters (kcat and Km) were more consistent with experimental values than those for catalytic efficiency (kcat/Km). Lastly, neural networks predicted correctly enantioselectivity and comparable catalytic parameters measured in this study for previously uncharacterized CYP2C19 substrates, R- and S-propranolol. Taken together, these seminal computational studies for CYP2C19 are the first to predict all catalytic parameters for enantioselective reactions using artificial neural networks and thus provide a foundation for expanding the prediction of cytochrome P450 reactions to chiral drugs, pollutants, and other biologically active compounds. PMID:23673224

Neural correlates of conscious self-regulation of emotion.

PubMed

Beauregard, M; Lévesque, J; Bourgouin, P

2001-09-15

A fundamental question about the relationship between cognition and emotion concerns the neural substrate underlying emotional self-regulation. To address this issue, brain activation was measured in normal male subjects while they either responded in a normal manner to erotic film excerpts or voluntarily attempted to inhibit the sexual arousal induced by viewing erotic stimuli. Results demonstrated that the sexual arousal experienced, in response to the erotic film excerpts, was associated with activation in "limbic" and paralimbic structures, such as the right amygdala, right anterior temporal pole, and hypothalamus. In addition, the attempted inhibition of the sexual arousal generated by viewing the erotic stimuli was associated with activation of the right superior frontal gyrus and right anterior cingulate gyrus. No activation was found in limbic areas. These findings reinforce the view that emotional self-regulation is normally implemented by a neural circuit comprising various prefrontal regions and subcortical limbic structures. They also suggest that humans have the capacity to influence the electrochemical dynamics of their brains, by voluntarily changing the nature of the mind processes unfolding in the psychological space.

What you see is what you eat: an ALE meta-analysis of the neural correlates of food viewing in children and adolescents.

PubMed

van Meer, Floor; van der Laan, Laura N; Adan, Roger A H; Viergever, Max A; Smeets, Paul A M

2015-01-01

Food cues are omnipresent and may enhance overconsumption. In the last two decades the prevalence of childhood obesity has increased dramatically all over the world, largely due to overconsumption. Understanding children's neural responses to food may help to develop better interventions for preventing or reducing overconsumption. We aimed to determine which brain regions are concurrently activated in children/adolescents in response to viewing food pictures, and how these relate to adult findings. Two activation likelihood estimation (ALE) meta-analyses were performed: one with studies in normal weight children/adolescents (aged 8-18, 8 studies, 137 foci) and one with studies in normal weight adults (aged 18-45, 16 studies, 178 foci). A contrast analysis was performed for children/adolescents vs. adults. In children/adolescents, the most concurrent clusters were in the left lateral orbitofrontal cortex (OFC), the bilateral fusiform gyrus, and the right superior parietal lobule. In adults, clusters in similar areas were found. Although the number of studies for a direct statistical comparison between the groups was relatively low, there were indications that children/adolescents may not activate areas important for cognitive control. Overall, the number of studies that contributed to the significant clusters was moderate (6-75%). In summary, the brain areas most consistently activated in children/adolescents by food viewing are part of the appetitive brain network and overlap with those found in adults. However, the age range of the children studied was rather broad. This study offers important recommendations for future research; studies making a direct comparison between adults and children in a sufficiently narrow age range would further elucidate how neural responses to food cues change during development. Copyright © 2014 Elsevier Inc. All rights reserved.

Murine Dishevelled 3 Functions in Redundant Pathways with Dishevelled 1 and 2 in Normal Cardiac Outflow Tract, Cochlea, and Neural Tube Development

PubMed Central

Etheridge, S. Leah; Ray, Saugata; Li, Shuangding; Hamblet, Natasha S.; Lijam, Nardos; Tsang, Michael; Greer, Joy; Kardos, Natalie; Wang, Jianbo; Sussman, Daniel J.; Chen, Ping; Wynshaw-Boris, Anthony

2008-01-01

Dishevelled (Dvl) proteins are important signaling components of both the canonical β-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP) pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE) movements that produce narrowing and elongation of the tissue. Three mammalian Dvl genes have been identified and the developmental roles of Dvl1 and Dvl2 were previously determined. Here, we identify the functions of Dvl3 in development and provide evidence of functional redundancy among the three murine Dvls. Dvl3 −/− mice died perinatally with cardiac outflow tract abnormalities, including double outlet right ventricle and persistent truncus arteriosis. These mutants also displayed a misorientated stereocilia in the organ of Corti, a phenotype that was enhanced with the additional loss of a single allele of the PCP component Vangl2/Ltap (LtapLp/+). Although neurulation appeared normal in both Dvl3 −/− and LtapLp/+ mutants, Dvl3 +/−;LtapLp/+ combined mutants displayed incomplete neural tube closure. Importantly, we show that many of the roles of Dvl3 are also shared by Dvl1 and Dvl2. More severe phenotypes were observed in Dvl3 mutants with the deficiency of another Dvl, and increasing Dvl dosage genetically with Dvl transgenes demonstrated the ability of Dvls to compensate for each other to enable normal development. Interestingly, global canonical Wnt signaling appeared largely unaffected in the double Dvl mutants, suggesting that low Dvl levels are sufficient for functional canonical Wnt signals. In summary, we demonstrate that Dvl3 is required for cardiac outflow tract development and describe its importance in the PCP pathway during neurulation and cochlea development. Finally, we establish several developmental processes in which the three Dvls are functionally redundant. PMID:19008950

Murine dishevelled 3 functions in redundant pathways with dishevelled 1 and 2 in normal cardiac outflow tract, cochlea, and neural tube development.

PubMed

Etheridge, S Leah; Ray, Saugata; Li, Shuangding; Hamblet, Natasha S; Lijam, Nardos; Tsang, Michael; Greer, Joy; Kardos, Natalie; Wang, Jianbo; Sussman, Daniel J; Chen, Ping; Wynshaw-Boris, Anthony

2008-11-01

Dishevelled (Dvl) proteins are important signaling components of both the canonical beta-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP) pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE) movements that produce narrowing and elongation of the tissue. Three mammalian Dvl genes have been identified and the developmental roles of Dvl1 and Dvl2 were previously determined. Here, we identify the functions of Dvl3 in development and provide evidence of functional redundancy among the three murine Dvls. Dvl3(-/-) mice died perinatally with cardiac outflow tract abnormalities, including double outlet right ventricle and persistent truncus arteriosis. These mutants also displayed a misorientated stereocilia in the organ of Corti, a phenotype that was enhanced with the additional loss of a single allele of the PCP component Vangl2/Ltap (LtapLp/+). Although neurulation appeared normal in both Dvl3(-/-) and LtapLp/+ mutants, Dvl3(+/-);LtapLp/+ combined mutants displayed incomplete neural tube closure. Importantly, we show that many of the roles of Dvl3 are also shared by Dvl1 and Dvl2. More severe phenotypes were observed in Dvl3 mutants with the deficiency of another Dvl, and increasing Dvl dosage genetically with Dvl transgenes demonstrated the ability of Dvls to compensate for each other to enable normal development. Interestingly, global canonical Wnt signaling appeared largely unaffected in the double Dvl mutants, suggesting that low Dvl levels are sufficient for functional canonical Wnt signals. In summary, we demonstrate that Dvl3 is required for cardiac outflow tract development and describe its importance in the PCP pathway during neurulation and cochlea development. Finally, we establish several developmental processes in which the three Dvls are functionally redundant.

The Interleukin 3 Gene (IL3) Contributes to Human Brain Volume Variation by Regulating Proliferation and Survival of Neural Progenitors

PubMed Central

Huang, Liang; Nho, Kwangsik; Deng, Min; Chen, Qiang; Weinberger, Daniel R.; Vasquez, Alejandro Arias; Rijpkema, Mark; Mattay, Venkata S.; Saykin, Andrew J.; Shen, Li; Fernández, Guillén; Franke, Barbara; Chen, Jing-chun; Chen, Xiang-ning; Wang, Jin-kai; Xiao, Xiao; Qi, Xue-bin; Xiang, Kun; Peng, Ying-Mei; Cao, Xiang-yu; Li, Yi; Shi, Xiao-dong; Gan, Lin; Su, Bing

2012-01-01

One of the most significant evolutionary changes underlying the highly developed cognitive abilities of humans is the greatly enlarged brain volume. In addition to being far greater than in most other species, the volume of the human brain exhibits extensive variation and distinct sexual dimorphism in the general population. However, little is known about the genetic mechanisms underlying normal variation as well as the observed sex difference in human brain volume. Here we show that interleukin-3 (IL3) is strongly associated with brain volume variation in four genetically divergent populations. We identified a sequence polymorphism (rs31480) in the IL3 promoter which alters the expression of IL3 by affecting the binding affinity of transcription factor SP1. Further analysis indicated that IL3 and its receptors are continuously expressed in the developing mouse brain, reaching highest levels at postnatal day 1–4. Furthermore, we found IL3 receptor alpha (IL3RA) was mainly expressed in neural progenitors and neurons, and IL3 could promote proliferation and survival of the neural progenitors. The expression level of IL3 thus played pivotal roles in the expansion and maintenance of the neural progenitor pool and the number of surviving neurons. Moreover, we found that IL3 activated both estrogen receptors, but estrogen didn’t directly regulate the expression of IL3. Our results demonstrate that genetic variation in the IL3 promoter regulates human brain volume and reveals novel roles of IL3 in regulating brain development. PMID:23226269

Dynamic network communication as a unifying neural basis for cognition, development, aging, and disease.

PubMed

Voytek, Bradley; Knight, Robert T

2015-06-15

Perception, cognition, and social interaction depend upon coordinated neural activity. This coordination operates within noisy, overlapping, and distributed neural networks operating at multiple timescales. These networks are built upon a structural scaffolding with intrinsic neuroplasticity that changes with development, aging, disease, and personal experience. In this article, we begin from the perspective that successful interregional communication relies upon the transient synchronization between distinct low-frequency (<80 Hz) oscillations, allowing for brief windows of communication via phase-coordinated local neuronal spiking. From this, we construct a theoretical framework for dynamic network communication, arguing that these networks reflect a balance between oscillatory coupling and local population spiking activity and that these two levels of activity interact. We theorize that when oscillatory coupling is too strong, spike timing within the local neuronal population becomes too synchronous; when oscillatory coupling is too weak, spike timing is too disorganized. Each results in specific disruptions to neural communication. These alterations in communication dynamics may underlie cognitive changes associated with healthy development and aging, in addition to neurological and psychiatric disorders. A number of neurological and psychiatric disorders-including Parkinson's disease, autism, depression, schizophrenia, and anxiety-are associated with abnormalities in oscillatory activity. Although aging, psychiatric and neurological disease, and experience differ in the biological changes to structural gray or white matter, neurotransmission, and gene expression, our framework suggests that any resultant cognitive and behavioral changes in normal or disordered states or their treatment are a product of how these physical processes affect dynamic network communication. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome

PubMed Central

Layman, W.S.; McEwen, D.P.; Beyer, L.A.; Lalani, S.R.; Fernbach, S.D.; Oh, E.; Swaroop, A.; Hegg, C.C.; Raphael, Y.; Martens, J.R.; Martin, D.M.

2009-01-01

Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies. The clinical features of CHARGE syndrome are highly variable and incompletely penetrant. Olfactory dysfunction is a common feature in CHARGE syndrome and has been potentially linked to primary olfactory bulb defects, but no data confirming this mechanistic link have been reported. On the basis of these observations, we hypothesized that loss of Chd7 disrupts mammalian olfactory tissue development and function. We found severe defects in olfaction in individuals with CHD7 mutations and CHARGE, and loss of odor evoked electro-olfactogram responses in Chd7 deficient mice, suggesting reduced olfaction is due to a dysfunctional olfactory epithelium. Chd7 expression was high in basal olfactory epithelial neural stem cells and down-regulated in mature olfactory sensory neurons. We observed smaller olfactory bulbs, reduced olfactory sensory neurons, and disorganized epithelial ultrastructure in Chd7 mutant mice, despite apparently normal functional cilia and sustentacular cells. Significant reductions in the proliferation of neural stem cells and regeneration of olfactory sensory neurons in the mature Chd7Gt/+ olfactory epithelium indicate critical roles for Chd7 in regulating neurogenesis. These studies provide evidence that mammalian olfactory dysfunction due to Chd7 haploinsufficiency is linked to primary defects in olfactory neural stem cell proliferation and may influence olfactory bulb development. PMID:19279158

Resting-State Functional Connectivity-Based Biomarkers and Functional MRI-Based Neurofeedback for Psychiatric Disorders: A Challenge for Developing Theranostic Biomarkers.

PubMed

Yamada, Takashi; Hashimoto, Ryu-Ichiro; Yahata, Noriaki; Ichikawa, Naho; Yoshihara, Yujiro; Okamoto, Yasumasa; Kato, Nobumasa; Takahashi, Hidehiko; Kawato, Mitsuo

2017-10-01

Psychiatric research has been hampered by an explanatory gap between psychiatric symptoms and their neural underpinnings, which has resulted in poor treatment outcomes. This situation has prompted us to shift from symptom-based diagnosis to data-driven diagnosis, aiming to redefine psychiatric disorders as disorders of neural circuitry. Promising candidates for data-driven diagnosis include resting-state functional connectivity MRI (rs-fcMRI)-based biomarkers. Although biomarkers have been developed with the aim of diagnosing patients and predicting the efficacy of therapy, the focus has shifted to the identification of biomarkers that represent therapeutic targets, which would allow for more personalized treatment approaches. This type of biomarker (i.e., "theranostic biomarker") is expected to elucidate the disease mechanism of psychiatric conditions and to offer an individualized neural circuit-based therapeutic target based on the neural cause of a condition. To this end, researchers have developed rs-fcMRI-based biomarkers and investigated a causal relationship between potential biomarkers and disease-specific behavior using functional MRI (fMRI)-based neurofeedback on functional connectivity. In this review, we introduce a recent approach for creating a theranostic biomarker, which consists mainly of 2 parts: (1) developing an rs-fcMRI-based biomarker that can predict diagnosis and/or symptoms with high accuracy, and (2) the introduction of a proof-of-concept study investigating the relationship between normalizing the biomarker and symptom changes using fMRI-based neurofeedback. In parallel with the introduction of recent studies, we review rs-fcMRI-based biomarker and fMRI-based neurofeedback, focusing on the technological improvements and limitations associated with clinical use. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Resting-State Functional Connectivity-Based Biomarkers and Functional MRI-Based Neurofeedback for Psychiatric Disorders: A Challenge for Developing Theranostic Biomarkers

PubMed Central

Yamada, Takashi; Hashimoto, Ryu-ichiro; Yahata, Noriaki; Ichikawa, Naho; Yoshihara, Yujiro; Okamoto, Yasumasa; Kato, Nobumasa; Takahashi, Hidehiko

2017-01-01

Abstract Psychiatric research has been hampered by an explanatory gap between psychiatric symptoms and their neural underpinnings, which has resulted in poor treatment outcomes. This situation has prompted us to shift from symptom-based diagnosis to data-driven diagnosis, aiming to redefine psychiatric disorders as disorders of neural circuitry. Promising candidates for data-driven diagnosis include resting-state functional connectivity MRI (rs-fcMRI)-based biomarkers. Although biomarkers have been developed with the aim of diagnosing patients and predicting the efficacy of therapy, the focus has shifted to the identification of biomarkers that represent therapeutic targets, which would allow for more personalized treatment approaches. This type of biomarker (i.e., “theranostic biomarker”) is expected to elucidate the disease mechanism of psychiatric conditions and to offer an individualized neural circuit-based therapeutic target based on the neural cause of a condition. To this end, researchers have developed rs-fcMRI-based biomarkers and investigated a causal relationship between potential biomarkers and disease-specific behavior using functional MRI (fMRI)-based neurofeedback on functional connectivity. In this review, we introduce a recent approach for creating a theranostic biomarker, which consists mainly of 2 parts: (1) developing an rs-fcMRI-based biomarker that can predict diagnosis and/or symptoms with high accuracy, and (2) the introduction of a proof-of-concept study investigating the relationship between normalizing the biomarker and symptom changes using fMRI-based neurofeedback. In parallel with the introduction of recent studies, we review rs-fcMRI-based biomarker and fMRI-based neurofeedback, focusing on the technological improvements and limitations associated with clinical use. PMID:28977523

Feedback associated with expectation for larger-reward improves visuospatial working memory performances in children with ADHD.

PubMed

Hammer, Rubi; Tennekoon, Michael; Cooke, Gillian E; Gayda, Jessica; Stein, Mark A; Booth, James R

2015-08-01

We tested the interactive effect of feedback and reward on visuospatial working memory in children with ADHD. Seventeen boys with ADHD and 17 Normal Control (NC) boys underwent functional magnetic resonance imaging (fMRI) while performing four visuospatial 2-back tasks that required monitoring the spatial location of letters presented on a display. Tasks varied in reward size (large; small) and feedback availability (no-feedback; feedback). While the performance of NC boys was high in all conditions, boys with ADHD exhibited higher performance (similar to those of NC boys) only when they received feedback associated with large-reward. Performance pattern in both groups was mirrored by neural activity in an executive function neural network comprised of few distinct frontal brain regions. Specifically, neural activity in the left and right middle frontal gyri of boys with ADHD became normal-like only when feedback was available, mainly when feedback was associated with large-reward. When feedback was associated with small-reward, or when large-reward was expected but feedback was not available, boys with ADHD exhibited altered neural activity in the medial orbitofrontal cortex and anterior insula. This suggests that contextual support normalizes activity in executive brain regions in children with ADHD, which results in improved working memory. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Brain-Derived Neurotrophic Factor (BDNF) Promotes Cochlear Spiral Ganglion Cell Survival and Function in Deafened, Developing Cats

PubMed Central

Leake, Patricia A.; Hradek, Gary T.; Hetherington, Alexander M.; Stakhovskaya, Olga

2011-01-01

Postnatal development and survival of spiral ganglion (SG) neurons depend upon both neural activity and neurotrophic support. Our previous studies showed that electrical stimulation from a cochlear implant only partly prevents SG degeneration after early deafness. Thus, neurotrophic agents that might be combined with an implant to improve neural survival are of interest. Recent studies reporting that BDNF promotes SG survival after deafness, have been conducted in rodents and limited to relatively short durations. Our study examined longer duration BDNF treatment in deafened cats that may better model the slow progression of SG degeneration in human cochleae and provides the first study of BDNF in the developing auditory system. Kittens were deafened neonatally, implanted at 4-5 weeks with intracochlear electrodes containing a drug-delivery cannula, and BDNF or artificial perilymph was infused for 10 weeks from a mini-osmotic pump. In BDNF-treated cochleae SG cells grew to normal size and were significantly larger than cells on the contralateral side. However, their morphology was not completely normal and many neurons lacked or had thinned perikaryl myelin. Unbiased stereology was employed to estimate SG cell density, independent of cell size. BDNF was effective in promoting significantly improved survival of SG neurons in these developing animals. BDNF treatment also resulted in higher density and larger size of myelinated radial nerve fibers, sprouting of fibers into the scala tympani, and improvement in electrically-evoked auditory brainstem response thresholds. Although BDNF may have potential therapeutic value in the developing auditory system, many serious obstacles currently preclude clinical application. PMID:21452221

Neuroprosthetics and Solutions for Restoring Sensorimotor Functions

DTIC Science & Technology

2009-01-01

in the stab wound control (A, C) and the 1-week implantation of the electrode (B, D). Striking neurofilament loss occurred surrounding both the stab...force. (Like in heel strike and toe of in normal gait cycle). (B) The Proof Test is a static test for foot ankle unit in which maximum load is...applied on heel and forefoot in one single time successively. Project 1. Develop a somatosensory neural interface (SSNI) -Completed pilot testing of

Sip1 mediates an E-cadherin-to-N-cadherin switch during cranial neural crest EMT

PubMed Central

Rogers, Crystal D.; Saxena, Ankur

2013-01-01

The neural crest, an embryonic stem cell population, initially resides within the dorsal neural tube but subsequently undergoes an epithelial-to-mesenchymal transition (EMT) to commence migration. Although neural crest and cancer EMTs are morphologically similar, little is known regarding conservation of their underlying molecular mechanisms. We report that Sip1, which is involved in cancer EMT, plays a critical role in promoting the neural crest cell transition to a mesenchymal state. Sip1 transcripts are expressed in premigratory/migrating crest cells. After Sip1 loss, the neural crest specifier gene FoxD3 was abnormally retained in the dorsal neuroepithelium, whereas Sox10, which is normally required for emigration, was diminished. Subsequently, clumps of adherent neural crest cells remained adjacent to the neural tube and aberrantly expressed E-cadherin while lacking N-cadherin. These findings demonstrate two distinct phases of neural crest EMT, detachment and mesenchymalization, with the latter involving a novel requirement for Sip1 in regulation of cadherin expression during completion of neural crest EMT. PMID:24297751

Human Frequency Following Response: Neural Representation of Envelope and Temporal Fine Structure in Listeners with Normal Hearing and Sensorineural Hearing Loss

PubMed Central

Ananthakrishnan, Saradha; Krishnan, Ananthanarayan; Bartlett, Edward

2015-01-01

Objective Listeners with sensorineural hearing loss (SNHL) typically experience reduced speech perception, which is not completely restored with amplification. This likely occurs because cochlear damage, in addition to elevating audiometric thresholds, alters the neural representation of speech transmitted to higher centers along the auditory neuroaxis. While the deleterious effects of SNHL on speech perception in humans have been well-documented using behavioral paradigms, our understanding of the neural correlates underlying these perceptual deficits remains limited. Using the scalp-recorded Frequency Following Response (FFR), the authors examine the effects of SNHL and aging on subcortical neural representation of acoustic features important for pitch and speech perception, namely the periodicity envelope (F0) and temporal fine structure (TFS) (formant structure), as reflected in the phase-locked neural activity generating the FFR. Design FFRs were obtained from 10 listeners with normal hearing (NH) and 9 listeners with mild-moderate SNHL in response to a steady-state English back vowel /u/ presented at multiple intensity levels. Use of multiple presentation levels facilitated comparisons at equal sound pressure level (SPL) and equal sensation level (SL). In a second follow-up experiment to address the effect of age on envelope and TFS representation, FFRs were obtained from 25 NH and 19 listeners with mild to moderately-severe SNHL to the same vowel stimulus presented at 80 dB SPL. Temporal waveforms, Fast Fourier Transform (FFT) and spectrograms were used to evaluate the magnitude of the phase-locked activity at F0 (periodicity envelope) and F1 (TFS). Results Neural representation of both envelope (F0) and TFS (F1) at equal SPLs was stronger in NH listeners compared to listeners with SNHL. Also, comparison of neural representation of F0 and F1 across stimulus levels expressed in SPL and SL (accounting for audibility) revealed that level-related changes in F0 and F1 magnitude were different for listeners with SNHL compared to listeners with normal hearing. Further, the degradation in subcortical neural representation was observed to persist in listeners with SNHL even when the effects of age were controlled for. Conclusions Overall, our results suggest a relatively greater degradation in the neural representation of TFS compared to periodicity envelope in individuals with SNHL. This degraded neural representation of TFS in SNHL, as reflected in the brainstem FFR, may reflect a disruption in the temporal pattern of phase-locked neural activity arising from altered tonotopic maps and/or wider filters causing poor frequency selectivity in these listeners. Lastly, while preliminary results indicate that the deleterious effects of SNHL may be greater than age-related degradation in subcortical neural representation, the lack of a balanced age-matched control group in this study does not permit us to completely rule out the effects of age on subcortical neural representation. PMID:26583482

Differences in Feedback- and Inhibition-Related Neural Activity in Adult ADHD

ERIC Educational Resources Information Center

Dibbets, Pauline; Evers, Lisbeth; Hurks, Petra; Marchetta, Natalie; Jolles, Jelle

2009-01-01

The objective of this study was to examine response inhibition- and feedback-related neural activity in adults with attention deficit hyperactivity disorder (ADHD) using event-related functional MRI. Sixteen male adults with ADHD and 13 healthy/normal controls participated in this study and performed a modified Go/NoGo task. Behaviourally,…

An Introduction to Normalization and Calibration Methods in Functional MRI

ERIC Educational Resources Information Center

Liu, Thomas T.; Glover, Gary H.; Mueller, Bryon A.; Greve, Douglas N.; Brown, Gregory G.

2013-01-01

In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes…

Learning and Generalization on Asynchrony and Order Tasks at Sound Offset: Implications for Underlying Neural Circuitry

ERIC Educational Resources Information Center

Mossbridge, Julia A.; Scissors, Beth N.; Wright, Beverly A.

2008-01-01

Normal auditory perception relies on accurate judgments about the temporal relationships between sounds. Previously, we used a perceptual-learning paradigm to investigate the neural substrates of two such relative-timing judgments made at sound onset: detecting stimulus asynchrony and discriminating stimulus order. Here, we conducted parallel…

Neurotrophic actions of dopamine on the development of a serotonergic feeding circuit in Drosophila melanogaster

PubMed Central

2012-01-01

Background In the fruit fly, Drosophila melanogaster, serotonin functions both as a neurotransmitter to regulate larval feeding, and in the development of the stomatogastric feeding circuit. There is an inverse relationship between neuronal serotonin levels during late embryogenesis and the complexity of the serotonergic fibers projecting from the larval brain to the foregut, which correlate with perturbations in feeding, the functional output of the circuit. Dopamine does not modulate larval feeding, and dopaminergic fibers do not innervate the larval foregut. Since dopamine can function in central nervous system development, separate from its role as a neurotransmitter, the role of neuronal dopamine was assessed on the development, and mature function, of the 5-HT larval feeding circuit. Results Both decreased and increased neuronal dopamine levels in late embryogenesis during development of this circuit result in depressed levels of larval feeding. Perturbations in neuronal dopamine during this developmental period also result in greater branch complexity of the serotonergic fibers innervating the gut, as well as increased size and number of the serotonin-containing vesicles along the neurite length. This neurotrophic action for dopamine is modulated by the D2 dopamine receptor expressed during late embryogenesis in central 5-HT neurons. Animals carrying transgenic RNAi constructs to knock down both dopamine and serotonin synthesis in the central nervous system display normal feeding and fiber architecture. However, disparate levels of neuronal dopamine and serotonin during development of the circuit result in abnormal gut fiber architecture and feeding behavior. Conclusions These results suggest that dopamine can exert a direct trophic influence on the development of a specific neural circuit, and that dopamine and serotonin may interact with each other to generate the neural architecture necessary for normal function of the circuit. PMID:22413901

High content screening of defined chemical libraries using normal and glioma-derived neural stem cell lines.

PubMed

Danovi, Davide; Folarin, Amos A; Baranowski, Bart; Pollard, Steven M

2012-01-01

Small molecules with potent biological effects on the fate of normal and cancer-derived stem cells represent both useful research tools and new drug leads for regenerative medicine and oncology. Long-term expansion of mouse and human neural stem cells is possible using adherent monolayer culture. These cultures represent a useful cellular resource to carry out image-based high content screening of small chemical libraries. Improvements in automated microscopy, desktop computational power, and freely available image processing tools, now means that such chemical screens are realistic to undertake in individual academic laboratories. Here we outline a cost effective and versatile time lapse imaging strategy suitable for chemical screening. Protocols are described for the handling and screening of human fetal Neural Stem (NS) cell lines and their malignant counterparts, Glioblastoma-derived neural stem cells (GNS). We focus on identification of cytostatic and cytotoxic "hits" and discuss future possibilities and challenges for extending this approach to assay lineage commitment and differentiation. Copyright © 2012 Elsevier Inc. All rights reserved.

Suggestion-Induced Modulation of Semantic Priming during Functional Magnetic Resonance Imaging

PubMed Central

Ulrich, Martin; Kiefer, Markus; Bongartz, Walter; Grön, Georg; Hoenig, Klaus

2015-01-01

Using functional magnetic resonance imaging during a primed visual lexical decision task, we investigated the neural and functional mechanisms underlying modulations of semantic word processing through hypnotic suggestions aimed at altering lexical processing of primes. The priming task was to discriminate between target words and pseudowords presented 200 ms after the prime word which was semantically related or unrelated to the target. In a counterbalanced study design, each participant performed the task once at normal wakefulness and once after the administration of hypnotic suggestions to perceive the prime as a meaningless symbol of a foreign language. Neural correlates of priming were defined as significantly lower activations upon semantically related compared to unrelated trials. We found significant suggestive treatment-induced reductions in neural priming, albeit irrespective of the degree of suggestibility. Neural priming was attenuated upon suggestive treatment compared with normal wakefulness in brain regions supporting automatic (fusiform gyrus) and controlled semantic processing (superior and middle temporal gyri, pre- and postcentral gyri, and supplementary motor area). Hence, suggestions reduced semantic word processing by conjointly dampening both automatic and strategic semantic processes. PMID:25923740

Explaining how brain stimulation can evoke memories.

PubMed

Jacobs, Joshua; Lega, Bradley; Anderson, Christopher

2012-03-01

An unexplained phenomenon in neuroscience is the discovery that electrical stimulation in temporal neocortex can cause neurosurgical patients to spontaneously experience memory retrieval. Here we provide the first detailed examination of the neural basis of stimulation-induced memory retrieval by probing brain activity in a patient who reliably recalled memories of his high school (HS) after stimulation at a site in his left temporal lobe. After stimulation, this patient performed a customized memory task in which he was prompted to retrieve information from HS and non-HS topics. At the one site where stimulation evoked HS memories, remembering HS information caused a distinctive pattern of neural activity compared with retrieving non-HS information. Together, these findings suggest that the patient had a cluster of neurons in his temporal lobe that help represent the "high school-ness" of the current cognitive state. We believe that stimulation here evoked HS memories because it altered local neural activity in a way that partially mimicked the normal brain state for HS memories. More broadly, our findings suggest that brain stimulation can evoke memories by recreating neural patterns from normal cognition.

The Potential Transformation of Our Species by Neural Enhancement

PubMed Central

Zehr, E. Paul

2015-01-01

ABSTRACT. Neural enhancement represents recovery of function that has been lost due to injury or disease pathology. Restoration of functional ability is the objective. For example, a neuroprosthetic to replace a forearm and hand lost to the ravages of war or industrial accident. However, the same basic constructs used for neural enhancement after injury could amplify abilities that are already in the natural normal range. That is, neural enhancement technologies to restore function and improve daily abilities for independent living could be used to improve so-called normal function to ultimate function. Approaching that functional level by use and integration of technology takes us toward the concept of a new species. This new subspecies—homo sapiens technologicus—is one that uses technology not just to assist but to change its own inherent biological function. The author uses examples from prosthetics and neuroprosthetics to address the issue of the limitations of constructs on the accepted range of human performance ability and aims to provide a cautionary view toward reflection on where our science may take the entire species. PMID:25575224

The Functional Neuroanatomy of Human Face Perception.

PubMed

Grill-Spector, Kalanit; Weiner, Kevin S; Kay, Kendrick; Gomez, Jesse

2017-09-15

Face perception is critical for normal social functioning and is mediated by a network of regions in the ventral visual stream. In this review, we describe recent neuroimaging findings regarding the macro- and microscopic anatomical features of the ventral face network, the characteristics of white matter connections, and basic computations performed by population receptive fields within face-selective regions composing this network. We emphasize the importance of the neural tissue properties and white matter connections of each region, as these anatomical properties may be tightly linked to the functional characteristics of the ventral face network. We end by considering how empirical investigations of the neural architecture of the face network may inform the development of computational models and shed light on how computations in the face network enable efficient face perception.

Planning Training Loads for the 400 M Hurdles in Three-Month Mesocycles using Artificial Neural Networks.

PubMed

Przednowek, Krzysztof; Iskra, Janusz; Wiktorowicz, Krzysztof; Krzeszowski, Tomasz; Maszczyk, Adam

2017-12-01

This paper presents a novel approach to planning training loads in hurdling using artificial neural networks. The neural models performed the task of generating loads for athletes' training for the 400 meters hurdles. All the models were calculated based on the training data of 21 Polish National Team hurdlers, aged 22.25 ± 1.96, competing between 1989 and 2012. The analysis included 144 training plans that represented different stages in the annual training cycle. The main contribution of this paper is to develop neural models for planning training loads for the entire career of a typical hurdler. In the models, 29 variables were used, where four characterized the runner and 25 described the training process. Two artificial neural networks were used: a multi-layer perceptron and a network with radial basis functions. To assess the quality of the models, the leave-one-out cross-validation method was used in which the Normalized Root Mean Squared Error was calculated. The analysis shows that the method generating the smallest error was the radial basis function network with nine neurons in the hidden layer. Most of the calculated training loads demonstrated a non-linear relationship across the entire competitive period. The resulting model can be used as a tool to assist a coach in planning training loads during a selected training period.

Abnormal Amygdalar Activation and Connectivity in Adolescents With Attention-Deficit/Hyperactivity Disorder

PubMed Central

Posner, Jonathan; Nagel, Bonnie J.; Maia, Tiago V.; Mechling, Anna; Oh, Milim; Wang, Zhishun; Peterson, Bradley S.

2011-01-01

Objective Emotional reactivity is one of the most disabling symptoms associated with ADHD. We aimed to identify neural substrates associated with emotional reactivity and assess the effects of stimulants on those substrates. Method We used functional magnetic resonance imaging (fMRI) to assess neural activity in adolescents with (N=15) and without (N=15) ADHD while they performed a task involving the subliminal presentation of fearful faces. Using dynamic causal modeling, we also examined the effective connectivity of two regions associated with emotional reactivity — the amygdala and the lateral prefrontal cortex (LPFC). The participants with ADHD were scanned both on and off stimulant medication in a counterbalanced fashion. Results During the task, we found that activity in the right amygdala was greater in adolescents with ADHD than in controls. Additionally, in adolescents with ADHD, greater connectivity was detected between the amygdala and LPFC. Stimulants had a normalizing effect on both the activity in the right amygdala and the connectivity between the amygdala and LPFC. Conclusions Our findings demonstrate that in adolescents with ADHD, a neural substrate of fear processing is atypical, as is the connectivity between the amygdala and LPFC. These findings suggest possible neural substrates for the emotional reactivity that is often present in youths with ADHD and provide putative neural targets for the development of novel therapeutic interventions for this condition. PMID:21784302

Planning Training Loads for the 400 M Hurdles in Three-Month Mesocycles using Artificial Neural Networks

PubMed Central

Iskra, Janusz; Wiktorowicz, Krzysztof; Krzeszowski, Tomasz; Maszczyk, Adam

2017-01-01

Abstract This paper presents a novel approach to planning training loads in hurdling using artificial neural networks. The neural models performed the task of generating loads for athletes’ training for the 400 meters hurdles. All the models were calculated based on the training data of 21 Polish National Team hurdlers, aged 22.25 ± 1.96, competing between 1989 and 2012. The analysis included 144 training plans that represented different stages in the annual training cycle. The main contribution of this paper is to develop neural models for planning training loads for the entire career of a typical hurdler. In the models, 29 variables were used, where four characterized the runner and 25 described the training process. Two artificial neural networks were used: a multi-layer perceptron and a network with radial basis functions. To assess the quality of the models, the leave-one-out cross-validation method was used in which the Normalized Root Mean Squared Error was calculated. The analysis shows that the method generating the smallest error was the radial basis function network with nine neurons in the hidden layer. Most of the calculated training loads demonstrated a non-linear relationship across the entire competitive period. The resulting model can be used as a tool to assist a coach in planning training loads during a selected training period. PMID:29339998

New animal models to study the role of tyrosinase in normal retinal development.

PubMed

Lavado, Alfonso; Montoliu, Lluis

2006-01-01

Albino animals display a hypopigmented phenotype associated with several visual abnormalities, including rod photoreceptor cell deficits, abnormal patterns of connections between the eye and the brain and a general underdevelopment of central retina. Oculocutaneous albinism type I, a common form of albinism, is caused by mutations in the tyrosinase gene. In mice, the albino phenotype can be corrected by functional tyrosinase transgenes. Tyrosinase transgenic animals not only show normal pigmentation but the correction of all visual abnormalities associated with albinism, confirming a role of tyrosinase, a key enzyme in melanin biosynthesis, in normal retinal development. Here, we will discuss recent work carried out with new tyrosinase transgenic mouse models, to further analyse the role of tyrosinase in retinal development. We will first report a transgenic model with inducible tyrosinase expression that has been used to address the regulated activation of this gene and its associated effects on the development of the visual system. Second, we will comment on an interesting yeast artificial chromosome (YAC)-tyrosinase transgene, lacking important regulatory elements, that has highlighted the significance of local interactions between the retinal pigment epithelium (RPE) and developing neural retina.

Postotic and preotic cranial neural crest cells differently contribute to thyroid development.

PubMed

Maeda, Kazuhiro; Asai, Rieko; Maruyama, Kazuaki; Kurihara, Yukiko; Nakanishi, Toshio; Kurihara, Hiroki; Miyagawa-Tomita, Sachiko

2016-01-01

Thyroid development and formation vary among species, but in most species the thyroid morphogenesis consists of five stages: specification, budding, descent, bilobation and folliculogenesis. The detailed mechanisms of these stages have not been fully clarified. During early development, the cranial neural crest (CNC) contributes to the thyroid gland. The removal of the postotic CNC (corresponding to rhombomeres 6, 7 and 8, also known as the cardiac neural crest) results in abnormalities of the cardiovascular system, thymus, parathyroid glands, and thyroid gland. To investigate the influence of the CNC on thyroid bilobation process, we divided the CNC into two regions, the postotic CNC and the preotic CNC (from the mesencephalon to rhombomere 5) regions and examined. We found that preotic CNC-ablated embryos had a unilateral thyroid lobe, and confirmed the presence of a single lobe or the absence of lobes in postotic CNC-ablated chick embryos. The thyroid anlage in each region-ablated embryos was of a normal size at the descent stage, but at a later stage, the thyroid in preotic CNC-ablated embryos was of a normal size, conflicting with a previous report in which the thyroid was reduced in size in the postotic CNC-ablated embryos. The postotic CNC cells differentiated into connective tissues of the thyroid in quail-to-chick chimeras. In contrast, the preotic CNC cells did not differentiate into connective tissues of the thyroid. We found that preotic CNC cells encompassed the thyroid anlage from the specification stage to the descent stage. Finally, we found that endothelin-1 and endothelin type A receptor-knockout mice and bosentan (endothelin receptor antagonist)-treated chick embryos showed bilobation anomalies that included single-lobe formation. Therefore, not only the postotic CNC, but also the preotic CNC plays an important role in thyroid morphogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Neural Decoding Reveals Impaired Face Configural Processing in the Right Fusiform Face Area of Individuals with Developmental Prosopagnosia

PubMed Central

Zhang, Jiedong; Liu, Jia

2015-01-01

Most of human daily social interactions rely on the ability to successfully recognize faces. Yet ∼2% of the human population suffers from face blindness without any acquired brain damage [this is also known as developmental prosopagnosia (DP) or congenital prosopagnosia]). Despite the presence of severe behavioral face recognition deficits, surprisingly, a majority of DP individuals exhibit normal face selectivity in the right fusiform face area (FFA), a key brain region involved in face configural processing. This finding, together with evidence showing impairments downstream from the right FFA in DP individuals, has led some to argue that perhaps the right FFA is largely intact in DP individuals. Using fMRI multivoxel pattern analysis, here we report the discovery of a neural impairment in the right FFA of DP individuals that may play a critical role in mediating their face-processing deficits. In seven individuals with DP, we discovered that, despite the right FFA's preference for faces and it showing decoding for the different face parts, it exhibited impaired face configural decoding and did not contain distinct neural response patterns for the intact and the scrambled face configurations. This abnormality was not present throughout the ventral visual cortex, as normal neural decoding was found in an adjacent object-processing region. To our knowledge, this is the first direct neural evidence showing impaired face configural processing in the right FFA in individuals with DP. The discovery of this neural impairment provides a new clue to our understanding of the neural basis of DP. PMID:25632131

Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

PubMed

Xu, Long-Chun; Zhang, Gang; Zou, Yue; Zhang, Min-Feng; Zhang, Dong-Sheng; Ma, Hua; Zhao, Wen-Bo; Zhang, Guang-Yu

2017-10-13

The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

Artificial Neural Network Based Fault Diagnostics of Rotating Machinery Using Wavelet Transforms as a Preprocessor

NASA Astrophysics Data System (ADS)

Paya, B. A.; Esat, I. I.; Badi, M. N. M.

1997-09-01

The purpose of condition monitoring and fault diagnostics are to detect and distinguish faults occurring in machinery, in order to provide a significant improvement in plant economy, reduce operational and maintenance costs and improve the level of safety. The condition of a model drive-line, consisting of various interconnected rotating parts, including an actual vehicle gearbox, two bearing housings, and an electric motor, all connected via flexible couplings and loaded by a disc brake, was investigated. This model drive-line was run in its normal condition, and then single and multiple faults were introduced intentionally to the gearbox, and to the one of the bearing housings. These single and multiple faults studied on the drive-line were typical bearing and gear faults which may develop during normal and continuous operation of this kind of rotating machinery. This paper presents the investigation carried out in order to study both bearing and gear faults introduced first separately as a single fault and then together as multiple faults to the drive-line. The real time domain vibration signals obtained for the drive-line were preprocessed by wavelet transforms for the neural network to perform fault detection and identify the exact kinds of fault occurring in the model drive-line. It is shown that by using multilayer artificial neural networks on the sets of preprocessed data by wavelet transforms, single and multiple faults were successfully detected and classified into distinct groups.

Development and Feasibility Assessment of a Rotational Orthosis for Walking with Arm Swing.

PubMed

Fang, Juan; Xie, Qing; Yang, Guo-Yuan; Xie, Le

2017-01-01

Interlimb neural coupling might underlie human bipedal locomotion, which is reflected in the fact that people swing their arms synchronously with leg movement in normal gait. Therefore, arm swing should be included in gait training to provide coordinated interlimb performance. The present study aimed to develop a Rotational Orthosis for Walking with Arm Swing (ROWAS), and evaluate its feasibility from the perspectives of implementation, acceptability and responsiveness. We developed the mechanical structures of the ROWAS system in SolidWorks, and implemented the concept in a prototype. Normal gait data were used as the reference performance of the shoulder, hip, knee and ankle joints of the prototype. The ROWAS prototype was tested for function assessment and further evaluated using five able-bodied subjects for user feedback. The ROWAS prototype produced coordinated performance in the upper and lower limbs, with joint profiles similar to those occurring in normal gait. The subjects reported a stronger feeling of walking with arm swing than without. The ROWAS system was deemed feasible according to the formal assessment criteria.

Development and Feasibility Assessment of a Rotational Orthosis for Walking with Arm Swing

PubMed Central

Fang, Juan; Xie, Qing; Yang, Guo-Yuan; Xie, Le

2017-01-01

Interlimb neural coupling might underlie human bipedal locomotion, which is reflected in the fact that people swing their arms synchronously with leg movement in normal gait. Therefore, arm swing should be included in gait training to provide coordinated interlimb performance. The present study aimed to develop a Rotational Orthosis for Walking with Arm Swing (ROWAS), and evaluate its feasibility from the perspectives of implementation, acceptability and responsiveness. We developed the mechanical structures of the ROWAS system in SolidWorks, and implemented the concept in a prototype. Normal gait data were used as the reference performance of the shoulder, hip, knee and ankle joints of the prototype. The ROWAS prototype was tested for function assessment and further evaluated using five able-bodied subjects for user feedback. The ROWAS prototype produced coordinated performance in the upper and lower limbs, with joint profiles similar to those occurring in normal gait. The subjects reported a stronger feeling of walking with arm swing than without. The ROWAS system was deemed feasible according to the formal assessment criteria. PMID:28203142

Central auditory neurons have composite receptive fields.

PubMed

Kozlov, Andrei S; Gentner, Timothy Q

2016-02-02

High-level neurons processing complex, behaviorally relevant signals are sensitive to conjunctions of features. Characterizing the receptive fields of such neurons is difficult with standard statistical tools, however, and the principles governing their organization remain poorly understood. Here, we demonstrate multiple distinct receptive-field features in individual high-level auditory neurons in a songbird, European starling, in response to natural vocal signals (songs). We then show that receptive fields with similar characteristics can be reproduced by an unsupervised neural network trained to represent starling songs with a single learning rule that enforces sparseness and divisive normalization. We conclude that central auditory neurons have composite receptive fields that can arise through a combination of sparseness and normalization in neural circuits. Our results, along with descriptions of random, discontinuous receptive fields in the central olfactory neurons in mammals and insects, suggest general principles of neural computation across sensory systems and animal classes.

Masking of infrared neural stimulation (INS) in hearing and deaf guinea pigs

NASA Astrophysics Data System (ADS)

Kadakia, Sama; Young, Hunter; Richter, Claus-Peter

2013-03-01

Spatial selective infrared neural stimulation has potential to improve neural prostheses, including cochlear implants. The heating of a confined target volume depolarizes the cell membrane and results in an action potential. Tissue heating may also results in thermal damage or the generation of a stress relaxation wave. Stress relaxation waves may result in a direct mechanical stimulation of remaining hair cells in the cochlea, so called optophony. Data are presented that quantify the effect of an acoustical stimulus (noise masker) on the response obtained with INS in normal hearing, acutely deafened, and chronic deaf animals. While in normal hearing animals an acoustic masker can reduce the response to INS, in acutely deafened animals the masking effect is reduced, and in chronic deaf animals this effect has not been detected. The responses to INS remain stable following the different degrees of cochlear damage.

Is the Cortical Deficit in Amblyopia Due to Reduced Cortical Magnification, Loss of Neural Resolution, or Neural Disorganization?

PubMed

Clavagnier, Simon; Dumoulin, Serge O; Hess, Robert F

2015-11-04

The neural basis of amblyopia is a matter of debate. The following possibilities have been suggested: loss of foveal cells, reduced cortical magnification, loss of spatial resolution of foveal cells, and topographical disarray in the cellular map. To resolve this we undertook a population receptive field (pRF) functional magnetic resonance imaging analysis in the central field in humans with moderate-to-severe amblyopia. We measured the relationship between averaged pRF size and retinal eccentricity in retinotopic visual areas. Results showed that cortical magnification is normal in the foveal field of strabismic amblyopes. However, the pRF sizes are enlarged for the amblyopic eye. We speculate that the pRF enlargement reflects loss of cellular resolution or an increased cellular positional disarray within the representation of the amblyopic eye. The neural basis of amblyopia, a visual deficit affecting 3% of the human population, remains a matter of debate. We undertook the first population receptive field functional magnetic resonance imaging analysis in participants with amblyopia and compared the projections from the amblyopic and fellow normal eye in the visual cortex. The projection from the amblyopic eye was found to have a normal cortical magnification factor, enlarged population receptive field sizes, and topographic disorganization in all early visual areas. This is consistent with an explanation of amblyopia as an immature system with a normal complement of cells whose spatial resolution is reduced and whose topographical map is disordered. This bears upon a number of competing theories for the psychophysical defect and affects future treatment therapies. Copyright © 2015 the authors 0270-6474/15/3514740-16$15.00/0.

Recovery from Posttraumatic Stress Requires Dynamic and Sequential Shifts in Amygdalar Connectivities

PubMed Central

Yoon, Sujung; Kim, Jieun E; Hwang, Jaeuk; Kang, Ilhyang; Jeon, Saerom; Im, Jooyeon J; Kim, Bori R; Lee, Sunho; Kim, Geon Ha; Rhim, Hyewhon; Lim, Soo Mee; Lyoo, In Kyoon

2017-01-01

The neural mechanisms underlying the development and maintenance of posttraumatic stress disorder (PTSD) have long been studied. However, little is known about the neural correlates of the recovery process from PTSD. A 5-year longitudinal study was conducted to investigate the trajectory of structural connectivities of the amygdala in disaster survivors with PTSD. Thirty disaster survivors, who were diagnosed with PTSD, and 29 healthy individuals, who were not exposed to trauma, underwent three waves of assessments including neuroimaging scanning over a 5-year period from the time of the disaster at approximately 1.3-year intervals. All disaster survivors showed significant improvements in PTSD symptoms over time. Using diffusion tensor imaging analysis, a 5-year trajectory of amygdalar structural connectivities with key brain regions was assessed. The amygdala–insula connection was initially strengthened and then normalized during recovery, while the amygdala–prefrontal cortex (PFC) connection was at first unaffected, then strengthened, and eventually normalized. The lower tract strength of the amygdala–thalamus connection normalized during recovery, while that of amygdala–hippocampus connection remained low. The greater amygdala–PFC connectivity was associated with less PTSD symptom severity. The present longitudinal study revealed that recovery from PTSD parallels dynamic and sequential shifts in amygdalar connectivities with multiple brain regions, suggesting the expanded view of fear circuitry including the insula and thalamus, beyond the traditional model which primarily involves the amygdala, PFC, and hippocampus. PMID:27461083

Visual influences on auditory spatial learning

PubMed Central

King, Andrew J.

2008-01-01

The visual and auditory systems frequently work together to facilitate the identification and localization of objects and events in the external world. Experience plays a critical role in establishing and maintaining congruent visual–auditory associations, so that the different sensory cues associated with targets that can be both seen and heard are synthesized appropriately. For stimulus location, visual information is normally more accurate and reliable and provides a reference for calibrating the perception of auditory space. During development, vision plays a key role in aligning neural representations of space in the brain, as revealed by the dramatic changes produced in auditory responses when visual inputs are altered, and is used throughout life to resolve short-term spatial conflicts between these modalities. However, accurate, and even supra-normal, auditory localization abilities can be achieved in the absence of vision, and the capacity of the mature brain to relearn to localize sound in the presence of substantially altered auditory spatial cues does not require visuomotor feedback. Thus, while vision is normally used to coordinate information across the senses, the neural circuits responsible for spatial hearing can be recalibrated in a vision-independent fashion. Nevertheless, early multisensory experience appears to be crucial for the emergence of an ability to match signals from different sensory modalities and therefore for the outcome of audiovisual-based rehabilitation of deaf patients in whom hearing has been restored by cochlear implantation. PMID:18986967

Neurovascular coupling and energy metabolism in the developing brain

PubMed Central

Kozberg, M.; Hillman, E.

2016-01-01

In the adult brain, increases in local neural activity are almost always accompanied by increases in local blood flow. However, many functional imaging studies of the newborn and developing human brain have observed patterns of hemodynamic responses that differ from adult responses. Among the proposed mechanisms for the observed variations is that neurovascular coupling itself is still developing in the perinatal brain. Many of the components thought to be involved in actuating and propagating this hemodynamic response are known to still be developing postnatally, including perivascular cells such as astrocytes and pericytes. Both neural and vascular networks expand and are then selectively pruned over the first year of human life. Additionally, the metabolic demands of the newborn brain are still evolving. These changes are highly likely to affect early postnatal neurovascular coupling, and thus may affect functional imaging signals in this age group. This chapter will discuss the literature relating to neurovascular development. Potential effects of normal and aberrant development of neurovascular coupling on the newborn brain will also be explored, as well as ways to effectively utilize imaging techniques that rely on hemodynamic modulation such as fMRI and NIRS in younger populations. PMID:27130418

Identification of pre-clinical Alzheimer’s disease by a profile of pathogenic proteins in neurally-derived blood exosomes: a case-control study

PubMed Central

Fiandaca, Massimo S.; Kapogiannis, Dimitrios; Mapstone, Mark; Boxer, Adam; Eitan, Erez; Schwartz, Janice B.; Abner, Erin L.; Petersen, Ronald C.; Federoff, Howard J.; Miller, Bruce L.; Goetzl, Edward J.

2014-01-01

Background Proteins pathogenic in Alzheimer’s disease (AD) were extracted from neurally-derived blood exosomes and quantified to develop biomarkers for staging of sporadic AD. Methods Blood exosomes obtained at one time-point from patients with AD (n=57) or frontotemporal dementia (FTD) (n=16), and at two time-points from others (n=24) when cognitively normal and one-ten years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD-pathogenic exosomal proteins were extracted and quantified by ELISAs. Results Mean exosomal levels of total Tau, P-T181-tau, P-S396-tau and Aβ1-42 for AD and levels of P-T181-tau and Aβ1-42 for FTD were significantly higher than for case-controls. Stepwise discriminant modeling incorporated P-T181-tau, P-S396-tau and Aβ1-42 in AD, but only P-T181-tau in FTD. Classification of 96.4% of AD patients and 87.5% of FTD patients was correct. In 24 AD patients, exosomal levels of P-S396-tau, P-T181-tau and Aβ1-42 were significantly higher than for controls both one to ten years before and when diagnosed with AD. Conclusions Levels of P-S396-tau, P-T181-tau and Aβ1-42 in extracts of neurally-derived blood exosomes predict development of AD up to 10 years prior to clinical onset. PMID:25130657

Sonic hedgehog is required for survival of both myogenic and chondrogenic somitic lineages.

PubMed

Teillet, M; Watanabe, Y; Jeffs, P; Duprez, D; Lapointe, F; Le Douarin, N M

1998-06-01

In vertebrates, the medial moieties of the somites give rise to the vertebrae and epaxial muscles, which develop in close relationship with the axial organs, neural tube and notochord. The lateral moieties contribute to the ribs and to limb and body wall muscles (hypaxial muscles) after a phase of lateral and ventral migration. Surgical ablation of the neural tube and notochord in the chick embryo during segmentation and early differentiation of the somites (day 2 of incubation) does not affect primary development of the hypaxial muscles, but leads to a complete absence of epaxial muscles, vertebrae and ribs, due to cell death in the somites. Here we demonstrate that cell death, which occurs within 24 hours of excision of the axial organs, affects both myogenic and chondrogenic cell lineages defined, respectively, by the expression of MyoD and Pax-1 genes. In contrast, Pax-3 transcripts, normally present in cells giving rise to hypaxial muscles, are preserved in the excised embryos. Backgrafting either the ventral neural tube or the notochord allows survival of MyoD- and Pax-1-expressing cells. Similarly, Sonic hedgehog-producing cells grafted in place of axial organs also rescue MyoD- and Pax-1-expressing cells from death and allow epaxial muscles, ribs and vertebrae to undergo organogenesis. These results demonstrate that the ventral neural tube and the notochord promote the survival of both myogenic and chondrogenic cell lineages in the somites and that this action is mediated by Sonic hedgehog.

Inactivation of Msx1 and Msx2 in neural crest reveals an unexpected role in suppressing heterotopic bone formation in the head

PubMed Central

Roybal, Paul G.; Wu, Nancy L.; Sun, Jingjing; Ting, Man-chun; Schaefer, Christopher; Maxson, Robert E.

2011-01-01

In an effort to understand the morphogenetic forces that shape the bones of the skull, we inactivated Msx1 and Msx2 conditionally in neural crest. We show that Wnt1-Cre inactivation of up to three Msx1/2 alleles results in a progressively larger defect in the neural crest-derived frontal bone. Unexpectedly, in embryos lacking all four Msx1/2 alleles, the large defect is filled in with mispatterned bone consisting of ectopic islands of bone between the reduced frontal bones, just anterior to the parietal bones. The bone is derived from neural crest, not mesoderm, and, from DiI cell marking experiments, originates in a normally non-osteogenic layer of cells through which the rudiment elongates apically. Associated with the heterotopic osteogeneis is an upregulation of Bmp signaling in this cell layer. Prevention of this upregulation by implantation of noggin-soaked beads in head explants also prevented heterotopic bone formation. These results suggest that Msx genes have a dual role in calvarial development: They are required for the differentiation and proliferation of osteogenic cells within rudiments, and they are also required to suppress an osteogenic program in a cell layer within which the rudiments grow. We suggest that the inactivation of this repressive activity may be one cause of Wormian bones, ectopic bones that are a feature of a variety of pathological conditions in which calvarial bone development is compromised. PMID:20398647

[Investigation of neural stem cell-derived donor contribution in the inner ear following blastocyst injection].

PubMed

Volkenstein, S; Brors, D; Hansen, S; Mlynski, R; Dinger, T C; Müller, A M; Dazert, S

2008-03-01

Utilising the enormous proliferation and multi-lineage differentiation potentials of somatic stem cells represents a possible therapeutical strategy for diseases of non-regenerative tissues like the inner ear. In the current study, the possibility of murine neural stem cells to contribute to the developing inner ear following blastocyst injection was investigated. Fetal brain-derived neural stem cells from the embryonic day 14 cortex of male mice were isolated and expanded for four weeks in neurobasal media supplemented with bFGF and EGF. Neural stem cells of male animals were harvested, injected into blastocysts and the blastocysts were transferred into pseudo-pregnant foster animals. Each blastocyst was injected with 5-15 microspheres growing from single cell suspension from neurospheres dissociated the day before. The resulting mice were investigated six months POST PARTUM for the presence of donor cells. Brainstem evoked response audiometry (BERA) was performed in six animals. To visualize donor cells Lac-Z staining was performed on sliced cochleas of two animals. In addition, the cochleas of four female animals were isolated and genomic DNA of the entire cochlea was analyzed for donor contribution by Y-chromosome-specific PCR. All animals had normal thresholds in brainstem evoked response audiometry. The male-specific PCR product indicating the presence of male donor cells were detected in the cochleas of three of the four female animals investigated. In two animals, male donor cells were detected unilateral, in one animal bilateral. The results suggest that descendants of neural stem cells are detectable in the inner ear after injection into blastocysts and possess the ability to integrate into the developing inner ear without obvious loss in hearing function.

Meninges: from protective membrane to stem cell niche

PubMed Central

Decimo, Ilaria; Fumagalli, Guido; Berton, Valeria; Krampera, Mauro; Bifari, Francesco

2012-01-01

Meninges are a three tissue membrane primarily known as coverings of the brain. More in depth studies on meningeal function and ultrastructure have recently changed the view of meninges as a merely protective membrane. Accurate evaluation of the anatomical distribution in the CNS reveals that meninges largely penetrate inside the neural tissue. Meninges enter the CNS by projecting between structures, in the stroma of choroid plexus and form the perivascular space (Virchow-Robin) of every parenchymal vessel. Thus, meninges may modulate most of the physiological and pathological events of the CNS throughout the life. Meninges are present since the very early embryonic stages of cortical development and appear to be necessary for normal corticogenesis and brain structures formation. In adulthood meninges contribute to neural tissue homeostasis by secreting several trophic factors including FGF2 and SDF-1. Recently, for the first time, we have identified the presence of a stem cell population with neural differentiation potential in meninges. In addition, we and other groups have further described the presence in meninges of injury responsive neural precursors. In this review we will give a comprehensive view of meninges and their multiple roles in the context of a functional network with the neural tissue. We will highlight the current literature on the developmental feature of meninges and their role in cortical development. Moreover, we will elucidate the anatomical distribution of the meninges and their trophic properties in adult CNS. Finally, we will emphasize recent evidences suggesting the potential role of meninges as stem cell niche harbouring endogenous precursors that can be activated by injury and are able to contribute to CNS parenchymal reaction. PMID:23671802

Zic1 and Zic4 regulate zebrafish roof plate specification and hindbrain ventricle morphogenesis

PubMed Central

Elsen, Gina E.; Choi, Louis; Millen, Kathleen; Grinblat, Yevgenya; Prince, Victoria E.

2008-01-01

During development, the lumen of the neural tube develops into a system of brain cavities or ventricles, which play important roles in normal CNS function. We have established that the formation of the hindbrain (4th) ventricle in zebrafish is dependent upon the pleiotropic functions of the genes implicated in human Dandy Walker Malformation, Zic1 and Zic4. Using morpholino knockdown we show that zebrafish Zic1 and Zic4 are required for normal morphogenesis of the 4th ventricle. In Zic1 and/or Zic4 morphants the ventricle does not open properly, but remains completely or partially fused from the level of rhombomere (r) 2 towards the posterior. In the absence of Zic function early hindbrain regionalization and neural crest development remain unaffected, but dorsal hindbrain progenitor cell proliferation is significantly reduced. Importantly, we find that Zic1 and Zic4 are required for development of the dorsal roof plate. In Zic morphants expression of roof plate markers, including lmx1b.1 and lmx1b.2, is disrupted. We further demonstrate that zebrafish Lmx1b function is required for both hindbrain roof plate development and 4th ventricle morphogenesis, confirming that roof plate formation is a critical component of ventricle development. Finally, we show that dorsal rhombomere boundary signaling centers depend on Zic1 and Zic4 function and on roof plate signals, and provide evidence that these boundary signals are also required for ventricle morphogenesis. In summary, we conclude that Zic1 and Zic4 control zebrafish 4th ventricle morphogenesis by regulating multiple mechanisms including cell proliferation and fate specification in the dorsal hindbrain. PMID:18191121

A Homolog of Subtilisin-Like Proprotein Convertase 7 Is Essential to Anterior Neural Development in Xenopus

PubMed Central

Senturker, Sema; Thomas, John Terrig; Mateshaytis, Jennifer; Moos, Malcolm

2012-01-01

Background Subtilisin-like Proprotein Convertase 7 (SPC7) is a member of the subtilisin/kexin family of pro-protein convertases. It cleaves many pro-proteins to release their active proteins, including members of the bone morphogenetic protein (BMP) family of signaling molecules. Other SPCs are known to be required during embryonic development but corresponding data regarding SPC7 have not been reported previously. Methodology/Principal Findings We demonstrated that Xenopus SPC7 (SPC7) was expressed predominantly in the developing brain and eye, throughout the neural plate initially, then more specifically in the lens and retina primordia as development progressed. Since no prior functional information has been reported for SPC7, we used gain- and loss-of-function experiments to investigate the possibility that it may also convey patterning or tissue specification information similarly to Furin, SPC4, and SPC6. Overexpression of SPC7 was without effect. In contrast, injection of SPC7 antisense morpholino oligonucleotides (MO) into a single blastomere at the 2- or 4-cell stage produced marked disruption of head structures; anophthalmia was salient. Bilateral injections suppressed head and eye formation completely. In parallel with suppression of eye and brain development by SPC7 knockdown, expression of early anterior neural markers (Sox2, Otx2, Rx2, and Pax6) and late eye-specific markers (β-Crystallin and Opsin), and of BMP target genes such as Tbx2 and Tbx3, was reduced or eliminated. Taken together, these findings suggest a critical role for SPC7–perhaps, at least in part, due to activation of one or more BMPs–in early patterning of the anterior neural plate and its derivatives. Conclusion/Significance SPC7 is required for normal development of the eye and brain, possibly through processing BMPs, though other potential substrates cannot be excluded. PMID:22761776

Musicians change their tune: how hearing loss alters the neural code.

PubMed

Parbery-Clark, Alexandra; Anderson, Samira; Kraus, Nina

2013-08-01

Individuals with sensorineural hearing loss have difficulty understanding speech, especially in background noise. This deficit remains even when audibility is restored through amplification, suggesting that mechanisms beyond a reduction in peripheral sensitivity contribute to the perceptual difficulties associated with hearing loss. Given that normal-hearing musicians have enhanced auditory perceptual skills, including speech-in-noise perception, coupled with heightened subcortical responses to speech, we aimed to determine whether similar advantages could be observed in middle-aged adults with hearing loss. Results indicate that musicians with hearing loss, despite self-perceptions of average performance for understanding speech in noise, have a greater ability to hear in noise relative to nonmusicians. This is accompanied by more robust subcortical encoding of sound (e.g., stimulus-to-response correlations and response consistency) as well as more resilient neural responses to speech in the presence of background noise (e.g., neural timing). Musicians with hearing loss also demonstrate unique neural signatures of spectral encoding relative to nonmusicians: enhanced neural encoding of the speech-sound's fundamental frequency but not of its upper harmonics. This stands in contrast to previous outcomes in normal-hearing musicians, who have enhanced encoding of the harmonics but not the fundamental frequency. Taken together, our data suggest that although hearing loss modifies a musician's spectral encoding of speech, the musician advantage for perceiving speech in noise persists in a hearing-impaired population by adaptively strengthening underlying neural mechanisms for speech-in-noise perception. Copyright © 2013 Elsevier B.V. All rights reserved.

Neural Correlates of Communication Skill and Symptom Severity in Autism: A Voxel-Based Morphometry Study

ERIC Educational Resources Information Center

Parks, Lauren K.; Hill, Dina E.; Thoma, Robert J.; Euler, Matthew J.; Lewine, Jeffrey D.; Yeo, Ronald A.

2009-01-01

Although many studies have compared the brains of normal controls and individuals with autism, especially older, higher-functioning individuals with autism, little is known of the neural correlates of the vast clinical heterogeneity characteristic of the disorder. In this study, we used voxel-based morphometry (VBM) to examine gray matter…

Normal and Abnormal Development of the Intrapericardial Arterial Trunks in Man and Mouse

PubMed Central

Anderson, Robert H.; Chaudhry, Bill; Mohun, Timothy J.; Bamforth, Simon D.; Hoyland, Darren; Phillips, Helen M.; Webb, Sandra; Moorman, Antoon F.J.; Brown, Nigel A.; Henderson, Deborah J.

2014-01-01

Aims The definitive cardiac outflow channels have three components: the intrapericardial arterial trunks; the arterial roots with valves; and the ventricular outflow tracts. We studied the normal and abnormal development of the most distal of these, the arterial trunks, comparing findings in mouse and man. Methods and Results Using lineage tracing and three-dimensional visualization by episcopic reconstruction and scanning electron microscopy, we studied embryonic day 9.5 to 12.5 mouse hearts, clarifying the development of the outflow tracts distal to the primordia of the arterial valves. We characterize a transient aortopulmonary foramen, located between the leading edge of a protrusion from the dorsal wall of the aortic sac and the distal margins of the two outflow cushions. The foramen is closed by fusion of the protrusion, with its cap of neural crest cells, with the neural crest cell-filled cushions; the resulting structure then functioning transiently as an aortopulmonary septum. Only subsequent to this closure is it possible to recognize, more proximally, the previously described aortopulmonary septal complex. The adjacent walls of the intrapericardial trunks are derived from the protrusion and distal parts of the outflow cushions, while the lateral walls are formed from intrapericardial extensions of pharyngeal mesenchyme derived from the second heart field. Conclusions We provide, for the first time, objective evidence of the mechanisms of closure of an aortopulmonary foramen that exists distally between the lumens of the developing intrapericardial arterial trunks. Our findings provide insights into the formation of aortopulmonary windows and the variants of common arterial trunk. PMID:22499773

Leptin and the brain: influences on brain development, cognitive functioning and psychiatric disorders.

PubMed

Farr, Olivia M; Tsoukas, Michael A; Mantzoros, Christos S

2015-01-01

Receptors of leptin, the prototypical adipokine, are expressed throughout the cortex and several other areas of the brain. Although typically studied for its role in energy intake and expenditure, leptin plays a critical role in many other neurocognitive processes and interacts with various other hormones and neurotransmitters to perform these functions. Here, we review the literature on how leptin influences brain development, neural degradation, Alzheimer's disease, psychiatric disorders, and more complicated cognitive functioning and feeding behaviors. We also discuss modulators of leptin and the leptin receptor as they relate to normal cognitive functioning and may mediate some of the actions of leptin in the brain. Although we are beginning to better understand the critical role leptin plays in normal cognitive functioning, there is much to be discovered. Copyright © 2015 Elsevier Inc. All rights reserved.

Sleep and Development in Genetically Tractable Model Organisms

PubMed Central

Kayser, Matthew S.; Biron, David

2016-01-01

Sleep is widely recognized as essential, but without a clear singular function. Inadequate sleep impairs cognition, metabolism, immune function, and many other processes. Work in genetic model systems has greatly expanded our understanding of basic sleep neurobiology as well as introduced new concepts for why we sleep. Among these is an idea with its roots in human work nearly 50 years old: sleep in early life is crucial for normal brain maturation. Nearly all known species that sleep do so more while immature, and this increased sleep coincides with a period of exuberant synaptogenesis and massive neural circuit remodeling. Adequate sleep also appears critical for normal neurodevelopmental progression. This article describes recent findings regarding molecular and circuit mechanisms of sleep, with a focus on development and the insights garnered from models amenable to detailed genetic analyses. PMID:27183564

Electrochemical Deposition of Nanostructured Conducting Polymer Coatings on Neural Prosthetic Devices

NASA Astrophysics Data System (ADS)

Yang, Junyan; Martin, David

2003-03-01

Micromachined neural prosthetic devices facilitate the functional stimulation of and recording from the central nervous system (CNS). These devices have been fabricated to consist of silicon shanks that have gold or iridium sites along their surface. Our goal is to improve the biocompatibility and long-term performance of the neural prosthetic probes when they are implanted chronically in the brain. In our most recent efforts we have established that electrochemical polymerization can be used to deposit fuzzy coatings of conducting polymers specifically on the electrode sites. For neural prosthetic devices that are intended for long term implantation, we need to develop surfaces that provide intimate contact and promote efficient signal transport at the interface of the microelectrode array and brain tissue. We have developed methods to rapidly and reliably fabricate nanostructured conducting polymer coatings on the electrode probes using templated and surfactant-mediated techniques. Conducting polymer nanomushrooms and nanohairs of polypyrrole (PPy) were electrochemically polymerized onto the functional sites of neural probes by using either nanoporous block copolymers thin films, "track-etched" polycarbonate films or anodic aluminium oxide membranes as templates. Nanofibers of conducting polymers have also been successfully obtained by polymerizations in the presence of surfactants. The influence of current density, monomer concentration, surfactant concentration, and deposition charge on the thickness and morphology of the nanostructured conducting polymer coatings has been studied by optical, scanned probe, scanning electron and transmission electron microscopy. As compared with the normal nodular morphology of polypyrrole, the nanostructured morphologies grown from the neural electrode result in fuzzy coatings with extremely high surface area. The electrical properties of the polymer coatings were studied by Impedance Spectroscopy (IS) and Cyclic Voltammetry (CV). The significant drop in impedance in magnitude and phase angle is consistent with an increase of the surface area due to the roughened surface morphology.

Disruption of the Flnb gene in mice phenocopies the human disease spondylocarpotarsal synostosis syndrome.

PubMed

Farrington-Rock, Claire; Kirilova, Veneta; Dillard-Telm, Lisa; Borowsky, Alexander D; Chalk, Sara; Rock, Matthew J; Cohn, Daniel H; Krakow, Deborah

2008-03-01

Spondylocarpotarsal synostosis syndrome (SCT) is an autosomal recessive disease that is characterized by short stature, and fusions of the vertebrae and carpal and tarsal bones. SCT results from homozygosity or compound heterozygosity for nonsense mutations in FLNB. FLNB encodes filamin B, a multifunctional cytoplasmic protein that plays a critical role in skeletal development. Protein extracts derived from cells of SCT patients with nonsense mutations in FLNB did not contain filamin B, demonstrating that SCT results from absence of filamin B. To understand the role of filamin B in skeletal development, an Flnb-/- mouse model was generated. The Flnb-/- mice were phenotypically similar to individuals with SCT as they exhibited short stature and similar skeletal abnormalities. Newborn Flnb-/- mice had fusions between the neural arches of the vertebrae in the cervical and thoracic spine. At postnatal day 60, the vertebral fusions were more widespread and involved the vertebral bodies as well as the neural arches. In addition, fusions were seen in sternum and carpal bones. Analysis of the Flnb-/- mice phenotype showed that an absence of filamin B causes progressive vertebral fusions, which is contrary to the previous hypothesis that SCT results from failure of normal spinal segmentation. These findings suggest that spinal segmentation can occur normally in the absence of filamin B, but the protein is required for maintenance of intervertebral, carpal and sternal joints, and the joint fusion process commences antenatally.

Tissue-specific targeting of Hsp26 has no effect on heat resistance of neural function in larval Drosophila.

PubMed

Mileva-Seitz, Viara; Xiao, Chengfeng; Seroude, Laurent; Robertson, R Meldrum

2008-01-01

Hsp26 belongs to the small heat-shock protein family and is normally expressed in all cells during heat stress. We aimed to determine if overexpression of this protein protects behavior and neural function in Drosophila melanogaster during heat stress, as has previously been shown for Hsp70. We used the UAS-GAL4 expression system to drive expression of Hsp26 in the whole animal (ubiquitously), in the motoneurons, and in the muscles of wandering third-instar larvae. There were slight increases in time to crawling failure and normalized excitatory junction potential (EJP) area for some of the transgenic lines, but these were not consistent. In addition, Hsp26 had no effect on the temperature at failure of EJPs, normalized EJP peak amplitude, and normalized EJP half-width. Overexpression larvae had a similar number of motoneuronal boutons and length of nerve terminals as controls, indicating that the occasional protective effects on locomotion were not due to changes at the synapse. We conclude that overexpression had a small thermoprotective effect on locomotion and no effect on neural function. As it has been shown that Hsp26 requires action of other Hsps to reactivate the denatured proteins to which it binds, we propose that at least in larvae, the function of Hsp26 was masked in the relative absence of other Hsps.

Mexican sign language recognition using normalized moments and artificial neural networks

NASA Astrophysics Data System (ADS)

Solís-V., J.-Francisco; Toxqui-Quitl, Carina; Martínez-Martínez, David; H.-G., Margarita

2014-09-01

This work presents a framework designed for the Mexican Sign Language (MSL) recognition. A data set was recorded with 24 static signs from the MSL using 5 different versions, this MSL dataset was captured using a digital camera in incoherent light conditions. Digital Image Processing was used to segment hand gestures, a uniform background was selected to avoid using gloved hands or some special markers. Feature extraction was performed by calculating normalized geometric moments of gray scaled signs, then an Artificial Neural Network performs the recognition using a 10-fold cross validation tested in weka, the best result achieved 95.83% of recognition rate.

Periconceptional Folic Acid Supplementation Benefit to Development of Early Sensory-Motor Function through Increase DNA Methylation in Rat Offspring

PubMed Central

Li, Wen; Li, Zhenshu; Li, Shou; Wang, Xinyan; Wilson, John X.; Huang, Guowei

2018-01-01

Periconceptional maternal folate levels may alter DNA methylation patterns and health outcomes in offspring. We hypothesized that maternal folic acid supplementation alters fetal neural development through DNA methylation in the fetal brain. Twenty-eight rats were randomly assigned to four groups: three groups of the female rats were fed folate-normal, folate-deficient or folate-supplemented diets from seven days before mating to delivery. In another group, folic acid supplementation diet short-period group was fed a folate-normal diet, except for 10 days (begin mating) when this group was fed a folate-supplemented diet. After delivery, the diets were changed to folate-normal diet for all four groups. The cliff avoidance and forelimb grip tests were used to assess sensory motor function of rat offspring. The results indicate that maternal folic acid supplementation improved the early development of sensory-motor function in offspring. Maternal folic acid supplementation increased the methylation potential, global DNA methylation (5-mC) and DNA methyltransferase expression and activity in the brains of the offspring. In conclusion, maternal folic acid supplementation increases DNA methylation pattern in offspring brain and improves the early development of sensory-motor function. PMID:29494536

Neural image analysis in the process of quality assessment: domestic pig oocytes

NASA Astrophysics Data System (ADS)

Boniecki, P.; Przybył, J.; Kuzimska, T.; Mueller, W.; Raba, B.; Lewicki, A.; Przybył, K.; Zaborowicz, M.; Koszela, K.

2014-04-01

The questions related to quality classification of animal oocytes are explored by numerous scientific and research centres. This research is important, particularly in the context of improving the breeding value of farm animals. The methods leading to the stimulation of normal development of a larger number of fertilised animal oocytes in extracorporeal conditions are of special importance. Growing interest in the techniques of supported reproduction resulted in searching for new, increasingly effective methods for quality assessment of mammalian gametes and embryos. Progress in the production of in vitro animal embryos in fact depends on proper classification of obtained oocytes. The aim of this paper was the development of an original method for quality assessment of oocytes, performed on the basis of their graphical presentation in the form of microscopic digital images. The classification process was implemented on the basis of the information coded in the form of microphotographic pictures of the oocytes of domestic pig, using the modern methods of neural image analysis.

Sonic Hedgehog modulates EGFR dependent proliferation of neural stem cells during late mouse embryogenesis through EGFR transactivation

PubMed Central

Reinchisi, Gisela; Parada, Margarita; Lois, Pablo; Oyanadel, Claudia; Shaughnessy, Ronan; Gonzalez, Alfonso; Palma, Verónica

2013-01-01

Sonic Hedgehog (Shh/GLI) and EGFR signaling pathways modulate Neural Stem Cell (NSC) proliferation. How these signals cooperate is therefore critical for understanding normal brain development and function. Here we report a novel acute effect of Shh signaling on EGFR function. We show that during late neocortex development, Shh mediates the activation of the ERK1/2 signaling pathway in Radial Glial cells (RGC) through EGFR transactivation. This process is dependent on metalloprotease activity and accounts for almost 50% of the EGFR-dependent mitogenic response of late NSCs. Furthermore, in HeLa cancer cells, a well-known model for studying the EGFR receptor function, Shh also induces cell proliferation involving EGFR activation, as reflected by EGFR internalization and ERK1/2 phosphorylation. These findings may have important implications for understanding the mechanisms that regulate NSC proliferation during neurogenesis and may lead to novel approaches to the treatment of tumors. PMID:24133411

Hippi is essential for node cilia assembly and Sonic hedgehog signaling

PubMed Central

Houde, Caroline; Dickinson, Robin J.; Houtzager, Vicky M.; Cullum, Rebecca; Montpetit, Rachel; Metzler, Martina; Simpson, Elizabeth M.; Roy, Sophie; Hayden, Michael R.; Hoodless, Pamela A.; Nicholson, Donald W.

2016-01-01

Hippi functions as an adapter protein that mediates pro-apoptotic signaling from poly-glutamine-expanded huntingtin, an established cause of Huntington disease, to the extrinsic cell death pathway. To explore other functions of Hippi we generated Hippi knock-out mice. This deletion causes randomization of the embryo turning process and heart looping, which are hallmarks of defective left–right (LR) axis patterning. We report that motile monocilia normally present at the surface of the embryonic node, and proposed to initiate the break in LR symmetry, are absent on Hippi−/− embryos. Furthermore, defects in central nervous system development are observed. The Sonic hedgehog (Shh) pathway is downregulated in the neural tube in the absence of Hippi, which results in failure to establish ventral neural cell fate. Together, these findings demonstrate a dual role for Hippi in cilia assembly and Shh signaling during development, in addition to its proposed role in apoptosis signal transduction in the adult brain under pathogenically stressful conditions. PMID:17027958

Localized states in an unbounded neural field equation with smooth firing rate function: a multi-parameter analysis.

PubMed

Faye, Grégory; Rankin, James; Chossat, Pascal

2013-05-01

The existence of spatially localized solutions in neural networks is an important topic in neuroscience as these solutions are considered to characterize working (short-term) memory. We work with an unbounded neural network represented by the neural field equation with smooth firing rate function and a wizard hat spatial connectivity. Noting that stationary solutions of our neural field equation are equivalent to homoclinic orbits in a related fourth order ordinary differential equation, we apply normal form theory for a reversible Hopf bifurcation to prove the existence of localized solutions; further, we present results concerning their stability. Numerical continuation is used to compute branches of localized solution that exhibit snaking-type behaviour. We describe in terms of three parameters the exact regions for which localized solutions persist.

Probing transcription-specific outputs of β-catenin in vivo.

PubMed

Valenta, Tomas; Gay, Max; Steiner, Sarah; Draganova, Kalina; Zemke, Martina; Hoffmans, Raymond; Cinelli, Paolo; Aguet, Michel; Sommer, Lukas; Basler, Konrad

2011-12-15

β-Catenin, apart from playing a cell-adhesive role, is a key nuclear effector of Wnt signaling. Based on activity assays in Drosophila, we generated mouse strains where the endogenous β-catenin protein is replaced by mutant forms, which retain the cell adhesion function but lack either or both of the N- and the C-terminal transcriptional outputs. The C-terminal activity is essential for mesoderm formation and proper gastrulation, whereas N-terminal outputs are required later during embryonic development. By combining the double-mutant β-catenin with a conditional null allele and a Wnt1-Cre driver, we probed the role of Wnt/β-catenin signaling in dorsal neural tube development. While loss of β-catenin protein in the neural tube results in severe cell adhesion defects, the morphology of cells and tissues expressing the double-mutant form is normal. Surprisingly, Wnt/β-catenin signaling activity only moderately regulates cell proliferation, but is crucial for maintaining neural progenitor identity and for neuronal differentiation in the dorsal spinal cord. Our model animals thus allow dissecting signaling and structural functions of β-catenin in vivo and provide the first genetic tool to generate cells and tissues that entirely and exclusively lack canonical Wnt pathway activity. © 2011 by Cold Spring Harbor Laboratory Press

Understanding the Basis of Auriculocondylar Syndrome: Insights From Human and Mouse Genetic Studies

PubMed Central

Clouthier, David E.; Passos Bueno, Maria Rita; Tavares, Andre L.P.; Lyonnet, Stanislas; Amiel, Jeanne; Gordon, Christopher T.

2014-01-01

Among human birth defect syndromes, malformations affecting the face are perhaps the most striking due to cultural and psychological expectations of facial shape. One such syndrome is auriculocondylar syndrome (ACS), in which patients present with defects in ear and mandible development. Affected structures arise from cranial neural crest cells, a population of cells in the embryo that reside in the pharyngeal arches and give rise to most of the bone, cartilage and connective tissue of the face. Recent studies have found that most cases of ACS arise from defects in signaling molecules associated with the endothelin signaling pathway. Disruption of this signaling pathway in both mouse and zebrafish results in loss of identity of neural crest cells of the mandibular portion of the first pharyngeal arch and the subsequent repatterning of these cells, leading to homeosis of lower jaw structures into more maxillary-like structures. These findings illustrate the importance of endothelin signaling in normal human craniofacial development and illustrate how clinical and basic science approaches can coalesce to improve our understanding of the genetic basis of human birth syndromes. Further, understanding the genetic basis for ACS that lies outside of known endothelin signaling components may help elucidate unknown aspects critical to the establishment of neural crest cell patterning during facial morphogenesis. PMID:24123988

Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure.

PubMed

Gavin, David P; Grayson, Dennis R; Varghese, Sajoy P; Guizzetti, Marina

2017-05-11

Prenatal alcohol exposure causes persistent neuropsychiatric deficits included under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges from a cascade of intrinsic and extrinsic (involving cell-cell interactions and signaling) processes that are partially initiated and maintained through changes in chromatin structure. Prenatal alcohol exposure influences neuronal and astrocyte development, permanently altering brain connectivity. Prenatal alcohol exposure also alters chromatin structure through histone and DNA modifications. However, the data linking alcohol-induced differentiation changes with developmental alterations in chromatin structure remain to be elucidated. In the first part of this review, we discuss the sequence of chromatin structural changes involved in neural cell differentiation during normal development. We then discuss the effects of prenatal alcohol on developmental histone modifications and DNA methylation in the context of neurogenesis and astrogliogenesis. We attempt to synthesize the developmental literature with the FASD literature, proposing that alcohol-induced changes to chromatin structure account for altered neurogenesis and astrogliogenesis as well as altered neuron and astrocyte differentiation. Together these changes may contribute to the cognitive and behavioral abnormalities in FASD. Future studies using standardized alcohol exposure paradigms at specific developmental stages will advance the understanding of how chromatin structural changes impact neural cell fate and maturation in FASD.

Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure

PubMed Central

Gavin, David P.; Grayson, Dennis R.; Varghese, Sajoy P.; Guizzetti, Marina

2017-01-01

Prenatal alcohol exposure causes persistent neuropsychiatric deficits included under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges from a cascade of intrinsic and extrinsic (involving cell-cell interactions and signaling) processes that are partially initiated and maintained through changes in chromatin structure. Prenatal alcohol exposure influences neuronal and astrocyte development, permanently altering brain connectivity. Prenatal alcohol exposure also alters chromatin structure through histone and DNA modifications. However, the data linking alcohol-induced differentiation changes with developmental alterations in chromatin structure remain to be elucidated. In the first part of this review, we discuss the sequence of chromatin structural changes involved in neural cell differentiation during normal development. We then discuss the effects of prenatal alcohol on developmental histone modifications and DNA methylation in the context of neurogenesis and astrogliogenesis. We attempt to synthesize the developmental literature with the FASD literature, proposing that alcohol-induced changes to chromatin structure account for altered neurogenesis and astrogliogenesis as well as altered neuron and astrocyte differentiation. Together these changes may contribute to the cognitive and behavioral abnormalities in FASD. Future studies using standardized alcohol exposure paradigms at specific developmental stages will advance the understanding of how chromatin structural changes impact neural cell fate and maturation in FASD. PMID:28492482

Augmented Indian hedgehog signaling in cranial neural crest cells leads to craniofacial abnormalities and dysplastic temporomandibular joint in mice

PubMed Central

Yang, Ling; Gu, Shuping; Ye, Wenduo; Song, Yingnan; Chen, YiPing

2016-01-01

Extensive studies have pinpointed the crucial role of Indian hedgehog (Ihh) signaling in the development of the appendicular skeleton and the essential function of Ihh in the formation of the temporomandibular joint (TMJ). In this study, we have investigated the effect of augmented Ihh signaling in TMJ development. We took a transgenic gain-of-function approach by overexpressing Ihh in the cranial neural crest (CNC) cells using a conditional Ihh transgenic allele and the Wnt1-Cre allele. We found that Wnt1-Cre-mediated tissue-specific overexpression of Ihh in the CNC lineage caused severe craniofacial abnormalities, including cleft lip/palate, encephalocele, anophthalmos, micrognathia, and defective TMJ development. In the mutant TMJ, the glenoid fossa was completely absent, whereas the condyle and the articular disc appeared relatively normal with slightly delayed chondrocyte differentiation. Our findings thus demonstrate that augmented Ihh signaling is detrimental to craniofacial development, and that finely tuned Ihh signaling is critical for TMJ formation. Our results also provide additional evidence that the development of the condyle and articular disc is independent of the glenoid fossa. PMID:26553654

The genetics of normal and defective color vision

PubMed Central

Neitz, Jay; Neitz, Maureen

2011-01-01

The contributions of genetics research to the science of normal and defective color vision over the previous few decades are reviewed emphasizing the developments in the 25 years since the last anniversary issue of Vision Research. Understanding of the biology underlying color vision has been vaulted forward through the application of the tools of molecular genetics. For all their complexity, the biological processes responsible for color vision are more accessible than for many other neural systems. This is partly because of the wealth of genetic variations that affect color perception, both within and across species, and because components of the color vision system lend themselves to genetic manipulation. Mutations and rearrangements in the genes encoding the long, middle, and short wavelength sensitive cone pigments are responsible for color vision deficiencies and mutations have been identified that affect the number of cone types, the absorption spectrum of the pigments, the functionality and viability of the cones, and the topography of the cone mosaic. The addition of an opsin gene, as occurred in the evolution of primate color vision, and has been done in experimental animals can produce expanded color vision capacities and this has provided insight into the underlying neural circuitry. PMID:21167193

Treatment of spinal fractures with paraplegia.

PubMed

Riska, E B; Myllynen, P

1981-01-01

Of 206 patients with vertebral fractures in the thoraco-lumbar spine with spinal cord injuries, an antero-lateral decompression with stabilization of the injured segment of the vertebral column was undertaken in 56 cases. In all these cases there was a compression of the spinal cord from the front. 8 patients made a complete recovery, 31 a good recovery, and 6 were improved. In 8 patients no improvement was noted. 2 patients developed pressure sores later and 1 patient died one year after the operation of uraemia. 22 patients out of 55 got a normal function of the bladder and 25 patients out of 54 a normal function of the anal sphincter. 16 patients out of 17 made a complete or good recovery after removal of a displaced rotated vertebral bony fragment from the spinal canal, and 7 patients out of 9 with wedge shaped fractures. In our clinic today, in cases of vertebral fractures with neural involvement, reduction and internal fixation with Harrington rods and fusion of the injured segment is undertaken as soon as possible, also during the night. If narrowing of the neural canal and compression of the spinal cord are verified, a decompression operation with interbody fusion is undertaken during the next days.

CRISPR-mediated genomic deletion of Sox2 in the axolotl shows a requirement in spinal cord neural stem cell amplification during tail regeneration.

PubMed

Fei, Ji-Feng; Schuez, Maritta; Tazaki, Akira; Taniguchi, Yuka; Roensch, Kathleen; Tanaka, Elly M

2014-09-09

The salamander is the only tetrapod that functionally regenerates all cell types of the limb and spinal cord (SC) and thus represents an important regeneration model, but the lack of gene-knockout technology has limited molecular analysis. We compared transcriptional activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPRs) in the knockout of three loci in the axolotl and find that CRISPRs show highly penetrant knockout with less toxic effects compared to TALENs. Deletion of Sox2 in up to 100% of cells yielded viable F0 larvae with normal SC organization and ependymoglial cell marker expression such as GFAP and ZO-1. However, upon tail amputation, neural stem cell proliferation was inhibited, resulting in spinal-cord-specific regeneration failure. In contrast, the mesodermal blastema formed normally. Sox3 expression during development, but not regeneration, most likely allowed embryonic survival and the regeneration-specific phenotype. This analysis represents the first tissue-specific regeneration phenotype from the genomic deletion of a gene in the axolotl. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Normalization regulates competition for visual awareness

PubMed Central

Ling, Sam; Blake, Randolph

2012-01-01

Summary Signals in our brain are in a constant state of competition, including those that vie for motor control, sensory dominance and awareness. To shed light on the mechanisms underlying neural competition, we exploit binocular rivalry, a phenomenon that allows us to probe the competitive process that ordinarily transpires outside of our awareness. By measuring psychometric functions under different states of rivalry, we discovered a pattern of gain changes that are consistent with a model of competition in which attention interacts with normalization processes, thereby driving the ebb and flow between states of awareness. Moreover, we reveal that attention plays a crucial role in modulating competition; without attention, rivalry suppression for high-contrast stimuli is negligible. We propose a framework whereby our visual awareness of competing sensory representations is governed by a common neural computation: normalization. PMID:22884335

Motor unit firing and its relation to tremor in the tonic vibration reflex of the decerebrate cat.

PubMed

Clark, F J; Matthews, P B; Muir, R B

1981-01-01

1. The discharge of single motor units has been recorded from the soleus muscle of the decerebrate cat during the tonic vibration reflex elicited isometrically, to further understanding of the tremor that is seen in the reflex contraction. The reflex was elicited by pulses of vibration of 50 micrometers amplitude at 150 Hz, and up to four units were studied concurrently. 2. Individual units fired rather regularly and at a low frequency (range 4-14 Hz). The rate of firing of any unit normally fell within the frequency band of the tremor recorded at the same time. On comparing different preparations a higher frequency of tremor was associated with a higher frequency of motor firing. 3. The responses of pairs of motor units recorded concurrently during repeated production of the reflex were compared by cross-correlation analysis; over 1000 spikes from each train were normally used for this. The major of the cross-correlograms were flat with no overt sign of any synchronization between the units other than that due to the vibration. 4. Clear indications of correlated motor unit firing could be produced deliberately by modulating the amplitude of vibration at a frequency comparable to that of the normal tremor and thereby introducing a rhythmic component into the tonic vibration reflex. 5. About 20% of the cross-correlograms obtained during normal tremor showed varying amounts of an irregular 'waviness' suggesting a possible correlation between the times of firing of a pair of units. But such waves never developed steadily throughout the period of analysis, in contrast to the comparable waves produced on modulating the vibration. Similar waves were seen on cross-correlating a motor unit with an electronic oscillator, confirming that their occurrence does not necessarily demonstrate the existence of active neural interactions. 6. It is concluded that there is no strong and widespread neural synchronizing mechanism active during the tonic vibration reflex, although the possibility of some weak neural interactions has not been excluded. The findings favour the idea that the tremor in this preparation is simply the inevitable result of motor units discharging asynchronously, but at closely similar subtetanic frequencies.

Neural responses during the anticipation and receipt of olfactory reward and punishment in human.

PubMed

Zou, Lai-Quan; Zhou, Han-Yu; Zhuang, Yuan; van Hartevelt, Tim J; Lui, Simon S Y; Cheung, Eric F C; Møller, Arne; Kringelbach, Morten L; Chan, Raymond C K

2018-03-01

Pleasure experience is an important part of normal healthy life and is essential for general and mental well-being. Many neuroimaging studies have investigated the underlying neural processing of verbal and visual modalities of reward. However, how the brain processes rewards in the olfactory modality is not fully understood. This study aimed to examine the neural basis of olfactory rewards in 25 healthy participants using functional magnetic resonance imaging (fMRI). We developed an Olfactory Incentive Delay (OLID) imaging task distinguishing between the anticipation and receipt of olfactory rewards and punishments. We found that the pallidum was activated during the anticipation of both olfactory rewards and punishments. The bilateral insula was activated independently from the odours' hedonic valence during the receipt phase. In addition, right caudate activation during the anticipation of unpleasant odours was correlated with self-reported anticipatory hedonic traits, whereas bilateral insular activation during the receipt of pleasant odours was correlated with self-reported consummatory hedonic traits. These findings suggest that activity in the insula and the caudate may be biomarkers of anhedonia. These findings also highlight a useful and valid paradigm to study the neural circuitry underlying reward processing in people with anhedonia. Copyright © 2018 Elsevier Ltd. All rights reserved.

Heterogeneity in perceptual category learning by high functioning children with autism spectrum disorder

PubMed Central

Mercado, Eduardo; Church, Barbara A.; Coutinho, Mariana V. C.; Dovgopoly, Alexander; Lopata, Christopher J.; Toomey, Jennifer A.; Thomeer, Marcus L.

2015-01-01

Previous research suggests that high functioning (HF) children with autism spectrum disorder (ASD) sometimes have problems learning categories, but often appear to perform normally in categorization tasks. The deficits that individuals with ASD show when learning categories have been attributed to executive dysfunction, general deficits in implicit learning, atypical cognitive strategies, or abnormal perceptual biases and abilities. Several of these psychological explanations for category learning deficits have been associated with neural abnormalities such as cortical underconnectivity. The present study evaluated how well existing neurally based theories account for atypical perceptual category learning shown by HF children with ASD across multiple category learning tasks involving novel, abstract shapes. Consistent with earlier results, children’s performances revealed two distinct patterns of learning and generalization associated with ASD: one was indistinguishable from performance in typically developing children; the other revealed dramatic impairments. These two patterns were evident regardless of training regimen or stimulus set. Surprisingly, some children with ASD showed both patterns. Simulations of perceptual category learning could account for the two observed patterns in terms of differences in neural plasticity. However, no current psychological or neural theory adequately explains why a child with ASD might show such large fluctuations in category learning ability across training conditions or stimulus sets. PMID:26157368

Neural network connectivity differences in children who stutter

PubMed Central

Zhu, David C.

2013-01-01

Affecting 1% of the general population, stuttering impairs the normally effortless process of speech production, which requires precise coordination of sequential movement occurring among the articulatory, respiratory, and resonance systems, all within millisecond time scales. Those afflicted experience frequent disfluencies during ongoing speech, often leading to negative psychosocial consequences. The aetiology of stuttering remains unclear; compared to other neurodevelopmental disorders, few studies to date have examined the neural bases of childhood stuttering. Here we report, for the first time, results from functional (resting state functional magnetic resonance imaging) and structural connectivity analyses (probabilistic tractography) of multimodal neuroimaging data examining neural networks in children who stutter. We examined how synchronized brain activity occurring among brain areas associated with speech production, and white matter tracts that interconnect them, differ in young children who stutter (aged 3–9 years) compared with age-matched peers. Results showed that children who stutter have attenuated connectivity in neural networks that support timing of self-paced movement control. The results suggest that auditory-motor and basal ganglia-thalamocortical networks develop differently in stuttering children, which may in turn affect speech planning and execution processes needed to achieve fluent speech motor control. These results provide important initial evidence of neurological differences in the early phases of symptom onset in children who stutter. PMID:24131593

Advances in Cochlear Implant Telemetry: Evoked Neural Responses, Electrical Field Imaging, and Technical Integrity

PubMed Central

Mens, Lucas H. M.

2007-01-01

During the last decade, cochlear implantation has evolved into a well-established treatment of deafness, predominantly because of many improvements in speech processing and the controlled excitation of the auditory nerve. Cochlear implants now also feature telemetry, which is highly useful to monitor the proper functioning of the implanted electronics and electrode contacts. Telemetry can also support the clinical management in young children and difficult cases where neural unresponsiveness is suspected. This article will review recent advances in the telemetry of the electrically evoked compound action potential that have made these measurements simple and routine procedures in most cases. The distribution of the electrical stimulus itself sampled by “electrical field imaging” reveals general patterns of current flow in the normal cochlea and gross abnormalities in individual patients; models have been developed to derive more subtle insights from an individual electrical field imaging. Finally, some thoughts are given to the extended application of telemetry, for example, in monitoring the neural responses or in combination with other treatments of the deaf ear. PMID:17709572

BDNF - A key player in cardiovascular system.

PubMed

Pius-Sadowska, Ewa; Machaliński, Bogusław

2017-09-01

Neurotrophins (NTs) were first identified as target-derived survival factors for neurons of the central and peripheral nervous system (PNS). They are known to control neural cell fate, development and function. Independently of their neuronal properties, NTs exert unique cardiovascular activity. The heart is innervated by sensory, sympathetic and parasympathetic neurons, which require NTs during early development and in the establishment of mature properties, contributing to the maintenance of cardiovascular homeostasis. The identification of molecular mechanisms regulated by NTs and involved in the crosstalk between cardiac sympathetic nerves, cardiomyocytes, cardiac fibroblasts, and vascular cells, has a fundamental importance in both normal heart function and disease. The article aims to review the recent data on the effects of Brain-Derived Neurotrophic Factor (BDNF) on various cardiovascular neuronal and non-neuronal functions such as the modulation of synaptic properties of autonomic neurons, axonal outgrowth and sprouting, formation of the vascular and neural networks, smooth muscle migration, and control of endothelial cell survival and cardiomyocytes. Understanding these mechanisms may be crucial for developing novel therapeutic strategies, including stem cell-based therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

MiRNA-128 regulates the proliferation and neurogenesis of neural precursors by targeting PCM1 in the developing cortex

PubMed Central

Zhang, Wei; Kim, Paul Jong; Chen, Zhongcan; Lokman, Hidayat; Qiu, Lifeng; Zhang, Ke; Rozen, Steven George; Tan, Eng King; Je, Hyunsoo Shawn; Zeng, Li

2016-01-01

During the development, tight regulation of the expansion of neural progenitor cells (NPCs) and their differentiation into neurons is crucial for normal cortical formation and function. In this study, we demonstrate that microRNA (miR)-128 regulates the proliferation and differentiation of NPCs by repressing pericentriolar material 1 (PCM1). Specifically, overexpression of miR-128 reduced NPC proliferation but promoted NPC differentiation into neurons both in vivo and in vitro. In contrast, the reduction of endogenous miR-128 elicited the opposite effects. Overexpression of miR-128 suppressed the translation of PCM1, and knockdown of endogenous PCM1 phenocopied the observed effects of miR-128 overexpression. Furthermore, concomitant overexpression of PCM1 and miR-128 in NPCs rescued the phenotype associated with miR-128 overexpression, enhancing neurogenesis but inhibiting proliferation, both in vitro and in utero. Taken together, these results demonstrate a novel mechanism by which miR-128 regulates the proliferation and differentiation of NPCs in the developing neocortex. DOI: http://dx.doi.org/10.7554/eLife.11324.001 PMID:26883496

Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure.

PubMed

Hamblet, Natasha S; Lijam, Nardos; Ruiz-Lozano, Pilar; Wang, Jianbo; Yang, Yasheng; Luo, Zhenge; Mei, Lin; Chien, Kenneth R; Sussman, Daniel J; Wynshaw-Boris, Anthony

2002-12-01

The murine dishevelled 2 (Dvl2) gene is an ortholog of the Drosophila segment polarity gene Dishevelled, a member of the highly conserved Wingless/Wnt developmental pathway. Dvl2-deficient mice were produced to determine the role of Dvl2 in mammalian development. Mice containing null mutations in Dvl2 present with 50% lethality in both inbred 129S6 and in a hybrid 129S6-NIH Black Swiss background because of severe cardiovascular outflow tract defects, including double outlet right ventricle, transposition of the great arteries and persistent truncus arteriosis. The majority of the surviving Dvl2(-/-) mice were female, suggesting that penetrance was influenced by sex. Expression of Pitx2 and plexin A2 was attenuated in Dvl2 null mutants, suggesting a defect in cardiac neural crest development during outflow tract formation. In addition, approximately 90% of Dvl2(-/-) mice have vertebral and rib malformations that affect the proximal as well as the distal parts of the ribs. These skeletal abnormalities were more pronounced in mice deficient for both Dvl1 and Dvl2. Somite differentiation markers used to analyze Dvl2(-/-) and Dvl1(-/-);Dvl2(-/-) mutant embryos revealed mildly aberrant expression of Uncx4.1, delta 1 and myogenin, suggesting defects in somite segmentation. Finally, 2-3% of Dvl2(-/-) embryos displayed thoracic spina bifida, while virtually all Dvl1/2 double mutant embryos displayed craniorachishisis, a completely open neural tube from the midbrain to the tail. Thus, Dvl2 is essential for normal cardiac morphogenesis, somite segmentation and neural tube closure, and there is functional redundancy between Dvl1 and Dvl2 in some phenotypes.

Application of artificial neural network model combined with four biomarkers in auxiliary diagnosis of lung cancer.

PubMed

Duan, Xiaoran; Yang, Yongli; Tan, Shanjuan; Wang, Sihua; Feng, Xiaolei; Cui, Liuxin; Feng, Feifei; Yu, Songcheng; Wang, Wei; Wu, Yongjun

2017-08-01

The purpose of the study was to explore the application of artificial neural network model in the auxiliary diagnosis of lung cancer and compare the effects of back-propagation (BP) neural network with Fisher discrimination model for lung cancer screening by the combined detections of four biomarkers of p16, RASSF1A and FHIT gene promoter methylation levels and the relative telomere length. Real-time quantitative methylation-specific PCR was used to detect the levels of three-gene promoter methylation, and real-time PCR method was applied to determine the relative telomere length. BP neural network and Fisher discrimination analysis were used to establish the discrimination diagnosis model. The levels of three-gene promoter methylation in patients with lung cancer were significantly higher than those of the normal controls. The values of Z(P) in two groups were 2.641 (0.008), 2.075 (0.038) and 3.044 (0.002), respectively. The relative telomere lengths of patients with lung cancer (0.93 ± 0.32) were significantly lower than those of the normal controls (1.16 ± 0.57), t = 4.072, P < 0.001. The areas under the ROC curve (AUC) and 95 % CI of prediction set from Fisher discrimination analysis and BP neural network were 0.670 (0.569-0.761) and 0.760 (0.664-0.840). The AUC of BP neural network was higher than that of Fisher discrimination analysis, and Z(P) was 0.76. Four biomarkers are associated with lung cancer. BP neural network model for the prediction of lung cancer is better than Fisher discrimination analysis, and it can provide an excellent and intelligent diagnosis tool for lung cancer.

Markov Chain Monte Carlo Bayesian Learning for Neural Networks

NASA Technical Reports Server (NTRS)

Goodrich, Michael S.

2011-01-01

Conventional training methods for neural networks involve starting al a random location in the solution space of the network weights, navigating an error hyper surface to reach a minimum, and sometime stochastic based techniques (e.g., genetic algorithms) to avoid entrapment in a local minimum. It is further typically necessary to preprocess the data (e.g., normalization) to keep the training algorithm on course. Conversely, Bayesian based learning is an epistemological approach concerned with formally updating the plausibility of competing candidate hypotheses thereby obtaining a posterior distribution for the network weights conditioned on the available data and a prior distribution. In this paper, we developed a powerful methodology for estimating the full residual uncertainty in network weights and therefore network predictions by using a modified Jeffery's prior combined with a Metropolis Markov Chain Monte Carlo method.

Taking a Toll on Self-Renewal: TLR-Mediated Innate Immune Signaling in Stem Cells.

PubMed

Alvarado, Alvaro G; Lathia, Justin D

2016-07-01

Innate immunity has evolved as the front-line cellular defense mechanism to acutely sense and decisively respond to microenvironmental alterations. The Toll-like receptor (TLR) family activates signaling pathways in response to stimuli and is well-characterized in both resident and infiltrating immune cells during neural inflammation, injury, and degeneration. Innate immune signaling has also been observed in neural cells during development and disease, including in the stem and progenitor cells that build the brain and are responsible for its homeostasis. Recently, the activation of developmental programs in malignant brain tumors has emerged as a driver for growth via cancer stem cells. In this review we discuss how innate immune signaling interfaces with stem cell maintenance in the normal and neoplastic brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tropical Timber Identification using Backpropagation Neural Network

NASA Astrophysics Data System (ADS)

Siregar, B.; Andayani, U.; Fatihah, N.; Hakim, L.; Fahmi, F.

2017-01-01

Each and every type of wood has different characteristics. Identifying the type of wood properly is important, especially for industries that need to know the type of timber specifically. However, it requires expertise in identifying the type of wood and only limited experts available. In addition, the manual identification even by experts is rather inefficient because it requires a lot of time and possibility of human errors. To overcome these problems, a digital image based method to identify the type of timber automatically is needed. In this study, backpropagation neural network is used as artificial intelligence component. Several stages were developed: a microscope image acquisition, pre-processing, feature extraction using gray level co-occurrence matrix and normalization of data extraction using decimal scaling features. The results showed that the proposed method was able to identify the timber with an accuracy of 94%.

Analysis and forecast of railway coal transportation volume based on BP neural network combined forecasting model

NASA Astrophysics Data System (ADS)

Xu, Yongbin; Xie, Haihong; Wu, Liuyi

2018-05-01

The share of coal transportation in the total railway freight volume is about 50%. As is widely acknowledged, coal industry is vulnerable to the economic situation and national policies. Coal transportation volume fluctuates significantly under the new economic normal. Grasp the overall development trend of railway coal transportation market, have important reference and guidance significance to the railway and coal industry decision-making. By analyzing the economic indicators and policy implications, this paper expounds the trend of the coal transportation volume, and further combines the economic indicators with the high correlation with the coal transportation volume with the traditional traffic prediction model to establish a combined forecasting model based on the back propagation neural network. The error of the prediction results is tested, which proves that the method has higher accuracy and has practical application.

System Identification for Nonlinear Control Using Neural Networks

NASA Technical Reports Server (NTRS)

Stengel, Robert F.; Linse, Dennis J.

1990-01-01

An approach to incorporating artificial neural networks in nonlinear, adaptive control systems is described. The controller contains three principal elements: a nonlinear inverse dynamic control law whose coefficients depend on a comprehensive model of the plant, a neural network that models system dynamics, and a state estimator whose outputs drive the control law and train the neural network. Attention is focused on the system identification task, which combines an extended Kalman filter with generalized spline function approximation. Continual learning is possible during normal operation, without taking the system off line for specialized training. Nonlinear inverse dynamic control requires smooth derivatives as well as function estimates, imposing stringent goals on the approximating technique.

An fMRI Investigation of the Neural Correlates Underlying the Processing of Novel Metaphoric Expressions

ERIC Educational Resources Information Center

Mashal, N.; Faust, M.; Hendler, T.; Jung-Beeman, M.

2007-01-01

The neural networks associated with processing related pairs of words forming literal, novel, and conventional metaphorical expressions and unrelated pairs of words were studied in a group of 15 normal adults using fMRI. Subjects read the four types of linguistic expressions and decided which relation exists between the two words (metaphoric,…

Patterns of brain reorganization subsequent to left fusiform damage: fMRI evidence from visual processing of words and pseudowords, faces and objects.

PubMed

Tsapkini, Kyrana; Vindiola, Manuel; Rapp, Brenda

2011-04-01

Little is known about the neural reorganization that takes place subsequent to lesions that affect orthographic processing (reading and/or spelling). We report on an fMRI investigation of an individual with a left mid-fusiform resection that affected both reading and spelling (Tsapkini & Rapp, 2010). To investigate possible patterns of functional reorganization, we compared the behavioral and neural activation patterns of this individual with those of a group of control participants for the tasks of silent reading of words and pseudowords and the passive viewing of faces and objects, all tasks that typically recruit the inferior temporal lobes. This comparison was carried out with methods that included a novel application of Mahalanobis distance statistics, and revealed: (1) normal behavioral and neural responses for face and object processing, (2) evidence of neural reorganization bilaterally in the posterior fusiform that supported normal performance in pseudoword reading and which contributed to word reading (3) evidence of abnormal recruitment of the bilateral anterior temporal lobes indicating compensatory (albeit insufficient) recruitment of mechanisms for circumventing the word reading deficit. Copyright © 2010 Elsevier Inc. All rights reserved.

Classification of antibiotics by neural network analysis of optical resonance data of whispering gallery modes in dielectric microspheres

NASA Astrophysics Data System (ADS)

Saetchnikov, Vladimir A.; Tcherniavskaia, Elina A.; Schweiger, Gustav; Ostendorf, Andreas

2012-04-01

A novel emerging technique for the label-free analysis of nanoparticles and biomolecules in liquid fluids using optical micro cavity resonance of whispering-gallery-type modes is being developed.A scheme based on polymer microspheres fixed by adhesive on the evanescence wave coupling element has been used. We demonstrated that the only spectral shift can't be used for identification of biological agents by developed approach. So neural network classifier for biological agents and micro/nano particles classification has been developed. The developed technique is the following. While tuning the laser wavelength images were recorded as avi-file. All sequences were broken into single frames and the location of the resonance was allocated in each frame. The image was filtered for noise reduction and integrated over two coordinates for evaluation of integrated energy of a measured signal. As input data normalized resonance shift of whispering-gallery modes and the relative efficiency of whispering-gallery modes excitation were used. Other parameters such as polarization of excited light, "center of gravity" of a resonance spectra etc. are also tested as input data for probabilistic neural network. After network designing and training we estimated the accuracy of classification. The classification of antibiotics such as penicillin and cephasolin have been performed with the accuracy of not less 97 %. Developed techniques can be used for lab-on-chip sensor based diagnostic tools as for identification of different biological molecules, e.g. proteins, oligonucleotides, oligosaccharides, lipids, small molecules, viral particles, cells and for dynamics of a delivery of medicines to bodies.

Neural bases of Theory of Mind in children with autism spectrum disorders and children with conduct problems and callous-unemotional traits.

PubMed

O'Nions, Elizabeth; Sebastian, Catherine L; McCrory, Eamon; Chantiluke, Kaylita; Happé, Francesca; Viding, Essi

2014-09-01

Individuals with autism spectrum disorders (ASD) have difficulty understanding other minds (Theory of Mind; ToM), with atypical processing evident at both behavioural and neural levels. Individuals with conduct problems and high levels of callous-unemotional (CU) traits (CP/HCU) exhibit reduced responsiveness to others' emotions and difficulties interacting with others, but nonetheless perform normally in experimental tests of ToM. The present study aimed to examine the neural underpinnings of ToM in children (aged 10-16) with ASD (N = 16), CP/HCU (N = 16) and typically developing (TD) controls (N = 16) using a non-verbal cartoon vignette task. Whilst individuals with ASD were predicted to show reduced fMRI responses across regions involved in ToM processing, CP/HCU individuals were predicted to show no differences compared with TD controls. The analyses indicated that neural responses did not differ between TD and CP/HCU groups during ToM. TD and CP/HCU children exhibited significantly greater medial prefrontal cortex responses during ToM than did the ASD group. Within the ASD group, responses in medial prefrontal cortex and right temporoparietal junction (TPJ) correlated with symptom severity as measured by the Autism Diagnostic Observation Schedule (ADOS). Findings suggest that although both ASD and CP/HCU are characterized by social difficulties, only children with ASD display atypical neural processing associated with ToM. © 2014 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.

PubMed

Zhukova, Nataliya; Ramaswamy, Vijay; Remke, Marc; Martin, Dianna C; Castelo-Branco, Pedro; Zhang, Cindy H; Fraser, Michael; Tse, Ken; Poon, Raymond; Shih, David J H; Baskin, Berivan; Ray, Peter N; Bouffet, Eric; Dirks, Peter; von Bueren, Andre O; Pfaff, Elke; Korshunov, Andrey; Jones, David T W; Northcott, Paul A; Kool, Marcel; Pugh, Trevor J; Pomeroy, Scott L; Cho, Yoon-Jae; Pietsch, Torsten; Gessi, Marco; Rutkowski, Stefan; Bognár, Laszlo; Cho, Byung-Kyu; Eberhart, Charles G; Conter, Cecile Faure; Fouladi, Maryam; French, Pim J; Grajkowska, Wieslawa A; Gupta, Nalin; Hauser, Peter; Jabado, Nada; Vasiljevic, Alexandre; Jung, Shin; Kim, Seung-Ki; Klekner, Almos; Kumabe, Toshihiro; Lach, Boleslaw; Leonard, Jeffrey R; Liau, Linda M; Massimi, Luca; Pollack, Ian F; Ra, Young Shin; Rubin, Joshua B; Van Meir, Erwin G; Wang, Kyu-Chang; Weiss, William A; Zitterbart, Karel; Bristow, Robert G; Alman, Benjamin; Hawkins, Cynthia E; Malkin, David; Clifford, Steven C; Pfister, Stefan M; Taylor, Michael D; Tabori, Uri

2014-12-24

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.

Estimation of cortical magnification from positional error in normally sighted and amblyopic subjects

PubMed Central

Hussain, Zahra; Svensson, Carl-Magnus; Besle, Julien; Webb, Ben S.; Barrett, Brendan T.; McGraw, Paul V.

2015-01-01

We describe a method for deriving the linear cortical magnification factor from positional error across the visual field. We compared magnification obtained from this method between normally sighted individuals and amblyopic individuals, who receive atypical visual input during development. The cortical magnification factor was derived for each subject from positional error at 32 locations in the visual field, using an established model of conformal mapping between retinal and cortical coordinates. Magnification of the normally sighted group matched estimates from previous physiological and neuroimaging studies in humans, confirming the validity of the approach. The estimate of magnification for the amblyopic group was significantly lower than the normal group: by 4.4 mm deg−1 at 1° eccentricity, assuming a constant scaling factor for both groups. These estimates, if correct, suggest a role for early visual experience in establishing retinotopic mapping in cortex. We discuss the implications of altered cortical magnification for cortical size, and consider other neural changes that may account for the amblyopic results. PMID:25761341

The different maturation of the corticospinal tract and corticoreticular pathway in normal brain development: diffusion tensor imaging study

PubMed Central

Yeo, Sang Seok; Jang, Sung Ho; Son, Su Min

2014-01-01

Background and Purpose: The corticospinal tract (CST) and corticoreticular pathway (CRP) are known to be important neural tracts for motor development. However, little is known about the difference in maturation of the CST and CRP. In this study, using diffusion tensor imaging (DTI), we investigated maturation of the CST and CRP in typically developed children and normal healthy adults. Methods: We recruited 75 normal healthy subjects for this study. DTI was performed using 1.5-T, and the CST and CRP were reconstructed using DTI-Studio software. Values of fractional anisotropy (FA) and fiber volume (FV) of the CST and CRP were measured. Results: In the current study, the threshold points for CST and CRP maturation were different in normal brain development. Change in FA value of the CST showed a steep increase until 7 years of age and then a gradual increase until adulthood, however, the CRP showed a steep increase only until 2 years of age and then a very gradual increase or plateau until adulthood. In terms of FV, the CST showed a steep increase until 12 years and then a gradual increase until adulthood, in contrast, the CRP showed gradual increase of FV across whole age range (0–25 years). Conclusion: The difference in maturation process between CST and CRP appears to be related to different periods of fine and gross motor development. This radiologic information can provide a scientific basis for understanding development in motor function. PMID:25309378

The Influence of Averageness on Adults' Perceptions of Attractiveness: The Effect of Early Visual Deprivation.

PubMed

Vingilis-Jaremko, Larissa; Maurer, Daphne; Rhodes, Gillian; Jeffery, Linda

2016-08-03

Adults who missed early visual input because of congenital cataracts later have deficits in many aspects of face processing. Here we investigated whether they make normal judgments of facial attractiveness. In particular, we studied whether their perceptions are affected normally by a face's proximity to the population mean, as is true of typically developing adults, who find average faces to be more attractive than most other faces. We compared the judgments of facial attractiveness of 12 cataract-reversal patients to norms established from 36 adults with normal vision. Participants viewed pairs of adult male and adult female faces that had been transformed 50% toward and 50% away from their respective group averages, and selected which face was more attractive. Averageness influenced patients' judgments of attractiveness, but to a lesser extent than controls. The results suggest that cataract-reversal patients are able to develop a system for representing faces with a privileged position for an average face, consistent with evidence from identity aftereffects. However, early visual experience is necessary to set up the neural architecture necessary for averageness to influence perceptions of attractiveness with its normal potency. © The Author(s) 2016.

Neurodynamic system theory: scope and limits.

PubMed

Erdi, P

1993-06-01

This paper proposes that neurodynamic system theory may be used to connect structural and functional aspects of neural organization. The paper claims that generalized causal dynamic models are proper tools for describing the self-organizing mechanism of the nervous system. In particular, it is pointed out that ontogeny, development, normal performance, learning, and plasticity, can be treated by coherent concepts and formalism. Taking into account the self-referential character of the brain, autopoiesis, endophysics and hermeneutics are offered as elements of a poststructuralist brain (-mind-computer) theory.

IDH1R132H in Neural Stem Cells: Differentiation Impaired by Increased Apoptosis

PubMed Central

Rosiak, Kamila; Smolarz, Maciej; Stec, Wojciech J.; Peciak, Joanna; Grzela, Dawid; Winiecka-Klimek, Marta; Stoczynska-Fidelus, Ewelina; Krynska, Barbara; Piaskowski, Sylwester; Rieske, Piotr

2016-01-01

Background The high frequency of mutations in the isocitrate dehydrogenase 1 (IDH1) gene in diffuse gliomas indicates its importance in the process of gliomagenesis. These mutations result in loss of the normal function and acquisition of the neomorphic activity converting α-ketoglutarate to 2-hydroxyglutarate. This potential oncometabolite may induce the epigenetic changes, resulting in the deregulated expression of numerous genes, including those related to the differentiation process or cell survivability. Methods Neural stem cells were derived from human induced pluripotent stem cells following embryoid body formation. Neural stem cells transduced with mutant IDH1R132H, empty vector, non-transduced and overexpressing IDH1WT controls were differentiated into astrocytes and neurons in culture. The neuronal and astrocytic differentiation was determined by morphology and expression of lineage specific markers (MAP2, Synapsin I and GFAP) as determined by real-time PCR and immunocytochemical staining. Apoptosis was evaluated by real-time observation of Caspase-3 activation and measurement of PARP cleavage by Western Blot. Results Compared with control groups, cells expressing IDH1R132H retained an undifferentiated state and lacked morphological changes following stimulated differentiation. The significant inhibitory effect of IDH1R132H on neuronal and astrocytic differentiation was confirmed by immunocytochemical staining for markers of neural stem cells. Additionally, real-time PCR indicated suppressed expression of lineage markers. High percentage of apoptotic cells was detected within IDH1R132H-positive neural stem cells population and their derivatives, if compared to normal neural stem cells and their derivatives. The analysis of PARP and Caspase-3 activity confirmed apoptosis sensitivity in mutant protein-expressing neural cells. Conclusions Our study demonstrates that expression of IDH1R132H increases apoptosis susceptibility of neural stem cells and their derivatives. Robust apoptosis causes differentiation deficiency of IDH1R132H-expressing cells. PMID:27145078

Surface electromyographic amplitude does not identify differences in neural drive to synergistic muscles.

PubMed

Martinez-Valdes, Eduardo; Negro, Francesco; Falla, Deborah; De Nunzio, Alessandro Marco; Farina, Dario

2018-04-01

Surface electromyographic (EMG) signal amplitude is typically used to compare the neural drive to muscles. We experimentally investigated this association by studying the motor unit (MU) behavior and action potentials in the vastus medialis (VM) and vastus lateralis (VL) muscles. Eighteen participants performed isometric knee extensions at four target torques [10, 30, 50, and 70% of the maximum torque (MVC)] while high-density EMG signals were recorded from the VM and VL. The absolute EMG amplitude was greater for VM than VL ( P < 0.001), whereas the EMG amplitude normalized with respect to MVC was greater for VL than VM ( P < 0.04). Because differences in EMG amplitude can be due to both differences in the neural drive and in the size of the MU action potentials, we indirectly inferred the neural drives received by the two muscles by estimating the synaptic inputs received by the corresponding motor neuron pools. For this purpose, we analyzed the increase in discharge rate from recruitment to target torque for motor units matched by recruitment threshold in the two muscles. This analysis indicated that the two muscles received similar levels of neural drive. Nonetheless, the size of the MU action potentials was greater for VM than VL ( P < 0.001), and this difference explained most of the differences in EMG amplitude between the two muscles (~63% of explained variance). These results indicate that EMG amplitude, even following normalization, does not reflect the neural drive to synergistic muscles. Moreover, absolute EMG amplitude is mainly explained by the size of MU action potentials. NEW & NOTEWORTHY Electromyographic (EMG) amplitude is widely used to compare indirectly the strength of neural drive received by synergistic muscles. However, there are no studies validating this approach with motor unit data. Here, we compared between-muscles differences in surface EMG amplitude and motor unit behavior. The results clarify the limitations of surface EMG to interpret differences in neural drive between muscles.

Auditory Processing in Noise Is Associated With Complex Patterns of Disrupted Functional Connectivity in Autism Spectrum Disorder

PubMed Central

Mamashli, Fahimeh; Khan, Sheraz; Bharadwaj, Hari; Michmizos, Konstantinos; Ganesan, Santosh; Garel, Keri-Lee A.; Hashmi, Javeria Ali; Herbert, Martha R.; Hämäläinen, Matti; Kenet, Tal

2017-01-01

Autism spectrum disorder (ASD) is associated with difficulty in processing speech in a noisy background, but the neural mechanisms that underlie this deficit have not been mapped. To address this question, we used magnetoencephalography to compare the cortical responses between ASD and typically developing (TD) individuals to a passive mismatch paradigm. We repeated the paradigm twice, once in a quiet background, and once in the presence of background noise. We focused on both the evoked mismatch field (MMF) response in temporal and frontal cortical locations, and functional connectivity with spectral specificity between those locations. In the quiet condition, we found common neural sources of the MMF response in both groups, in the right temporal gyrus and inferior frontal gyrus (IFG). In the noise condition, the MMF response in the right IFG was preserved in the TD group, but reduced relative to the quiet condition in ASD group. The MMF response in the right IFG also correlated with severity of ASD. Moreover, in noise, we found significantly reduced normalized coherence (deviant normalized by standard) in ASD relative to TD, in the beta band (14–25 Hz), between left temporal and left inferior frontal sub-regions. However, unnormalized coherence (coherence during deviant or standard) was significantly increased in ASD relative to TD, in multiple frequency bands. Our findings suggest increased recruitment of neural resources in ASD irrespective of the task difficulty, alongside a reduction in top-down modulations, usually mediated by the beta band, needed to mitigate the impact of noise on auditory processing. PMID:27910247

Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects

PubMed Central

Nie, Xuguang; Deng, Chu-xia; Wang, Qin; Jiao, Kai

2008-01-01

TGFβ/BMP signaling pathways are essential for normal development of neural crest cells (NCCs). Smad4 encodes the only common Smad protein in mammals, which is a critical nuclear mediator of TGFβ/BMP signaling. In this work, we sought to investigate the roles of Smad4 for development of NCCs. To overcome the early embryonic lethality of Smad4 null mice, we specifically disrupted Smad4 in NCCs using a Cre/loxP system. The mutant mice died at mid-gestation with defects in facial primordia, pharyngeal arches, outflow tract and cardiac ventricles. Further examination revealed that mutant embryos displayed severe molecular defects starting from E9.5. Expression of multiple genes, including Msx1, 2, Ap-2α, Pax3, and Sox9, which play critical roles for NCC development, was downregulated by NCC disruption of Smad4. Moreover, increased cell death was observed in pharyngeal arches from E10.5. However, the cell proliferation rate in these areas was not substantially altered. Taken together, these findings provide compelling genetic evidence that Smad4-mediated activities of TGFβ/BMP signals are essential for appropriate NCC development. PMID:18334251

Anatomy and development of the macula: specialisation and the vulnerability to macular degeneration.

PubMed

Provis, Jan M; Penfold, Philip L; Cornish, Elisa E; Sandercoe, Trent M; Madigan, Michele C

2005-09-01

The central retina in primates is adapted for high acuity vision. The most significant adaptations to neural retina in this respect are: 1. The very high density of cone photoreceptors on the visual axis; 2. The dominance of Midget pathways arising from these cones and 3. The diminishment of retinal blood supply in the macula, and its absence on the visual axis. Restricted blood supply to the part of the retina that has the highest density of neural elements is paradoxical. Inhibition of vascular growth and proliferation is evident during foetal life and results in metabolic stress in ganglion cells and Muller cells, which is resolved during formation of the foveal depression. In this review we argue that at the macula stressed retinal neurons adapt during development to a limited blood supply from the choriocapillaris, which supplies little in excess of metabolic demand of the neural retina under normal conditions. We argue also that while adaptation of the choriocapillaris underlying the foveal region may initially augment the local supply of oxygen and nutrients by diffusion, in the long term these adaptations make the region more vulnerable to age-related changes, including the accumulation of insoluble material in Bruch's membrane and beneath the retinal pigment epithelium. These changes eventually impact on delivery of oxygen and nutrients to the RPE and outer neural retina because of reduced flow in the choriocapillaris and the increasing barriers to effective diffusion. Both the inflammatory response and the sequelae of oxidative stress are predictable outcomes in this scenario.

Defective pulmonary innervation and autonomic imbalance in congenital diaphragmatic hernia

PubMed Central

Lath, Nikesh R.; Galambos, Csaba; Rocha, Alejandro Best; Malek, Marcus; Gittes, George K.

2012-01-01

Congenital diaphragmatic hernia (CDH) is associated with significant mortality due to lung hypoplasia and pulmonary hypertension. The role of embryonic pulmonary innervation in normal lung development and lung maldevelopment in CDH has not been defined. We hypothesize that developmental defects of intrapulmonary innervation, in particular autonomic innervation, occur in CDH. This abnormal embryonic pulmonary innervation may contribute to lung developmental defects and postnatal physiological derangement in CDH. To define patterns of pulmonary innervation in CDH, human CDH and control lung autopsy specimens were stained with the pan-neural marker S-100. To further characterize patterns of overall and autonomic pulmonary innervation during lung development in CDH, the murine nitrofen model of CDH was utilized. Immunostaining for protein gene product 9.5 (a pan-neuronal marker), tyrosine hydroxylase (a sympathetic marker), vesicular acetylcholine transporter (a parasympathetic marker), or VIP (a parasympathetic marker) was performed on lung whole mounts and analyzed via confocal microscopy and three-dimensional reconstruction. Peribronchial and perivascular neuronal staining pattern is less complex in human CDH than control lung. In mice, protein gene product 9.5 staining reveals less complex neuronal branching and decreased neural tissue in nitrofen-treated lungs from embryonic day 12.5 to 16.5 compared with controls. Furthermore, nitrofen-treated embryonic lungs exhibited altered autonomic innervation, with a relative increase in sympathetic nerve staining and a decrease in parasympathetic nerve staining compared with controls. These results suggest a primary defect in pulmonary neural developmental in CDH, resulting in less complex neural innervation and autonomic imbalance. Defective embryonic pulmonary innervation may contribute to lung developmental defects and postnatal physiological derangement in CDH. PMID:22114150

[Neural activity related to emotional and empathic deficits in subjects with post-traumatic stress disorder who survived the L'Aquila (Central Italy) 2009 earthquake].

PubMed

Mazza, Monica; Pino, Maria Chiara; Tempesta, Daniela; Catalucci, Alessia; Masciocchi, Carlo; Ferrara, Michele

2016-01-01

Post-Traumatic Stress Disorder (PTSD) is a chronic anxiety disorder. The continued efforts to control the distressing memories by traumatized individuals, together with the reduction of responsiveness to the outside world, are called Emotional Numbing (EN). The EN is one of the central symptoms in PTSD and it plays an integral role not only in the development and maintenance of post-traumatic symptomatology, but also in the disability of emotional regulation. This disorder shows an abnormal response of cortical and limbic regions which are normally involved in understanding emotions since the very earliest stages of the development of processing ability. Patients with PTSD exhibit exaggerated brain responses to emotionally negative stimuli. Identifying the neural correlates of emotion regulation in these subjects is important for elucidating the neural circuitry involved in emotional and empathic dysfunction. We showed that PTSD patients, all survivors of the L'Aquila 2009 earthquake, have a higher sensitivity to negative emotion and lower empathy levels. These emotional and empathic deficits are accompanied by neural brain functional correlates. Indeed PTSD subjects exhibit functional abnormalities in brain regions that are involved in stress regulation and emotional responses. The reduced activation of the frontal areas and a stronger activation of the limbic areas when responding to emotional stimuli could lead the subjects to enact coping strategies aimed at protecting themselves from the re-experience of pain related to traumatic events. This would result in a dysfunctional hyperactivation of subcortical areas, which may cause emotional distress and, consequently, impaired social relationships often reported by PTSD patients.

Sleep and Development in Genetically Tractable Model Organisms.

PubMed

Kayser, Matthew S; Biron, David

2016-05-01

Sleep is widely recognized as essential, but without a clear singular function. Inadequate sleep impairs cognition, metabolism, immune function, and many other processes. Work in genetic model systems has greatly expanded our understanding of basic sleep neurobiology as well as introduced new concepts for why we sleep. Among these is an idea with its roots in human work nearly 50 years old: sleep in early life is crucial for normal brain maturation. Nearly all known species that sleep do so more while immature, and this increased sleep coincides with a period of exuberant synaptogenesis and massive neural circuit remodeling. Adequate sleep also appears critical for normal neurodevelopmental progression. This article describes recent findings regarding molecular and circuit mechanisms of sleep, with a focus on development and the insights garnered from models amenable to detailed genetic analyses. Copyright © 2016 by the Genetics Society of America.

Synaptic up-scaling preserves motor circuit output after chronic, natural inactivity

PubMed Central

Vallejo, Mauricio; Hartzler, Lynn K

2017-01-01

Neural systems use homeostatic plasticity to maintain normal brain functions and to prevent abnormal activity. Surprisingly, homeostatic mechanisms that regulate circuit output have mainly been demonstrated during artificial and/or pathological perturbations. Natural, physiological scenarios that activate these stabilizing mechanisms in neural networks of mature animals remain elusive. To establish the extent to which a naturally inactive circuit engages mechanisms of homeostatic plasticity, we utilized the respiratory motor circuit in bullfrogs that normally remains inactive for several months during the winter. We found that inactive respiratory motoneurons exhibit a classic form of homeostatic plasticity, up-scaling of AMPA-glutamate receptors. Up-scaling increased the synaptic strength of respiratory motoneurons and acted to boost motor amplitude from the respiratory network following months of inactivity. Our results show that synaptic scaling sustains strength of the respiratory motor output following months of inactivity, thereby supporting a major neuroscience hypothesis in a normal context for an adult animal. PMID:28914603

Personality dimensions of people who suffer from visual stress.

PubMed

Hollis, J; Allen, P M; Fleischmann, D; Aulak, R

2007-11-01

Personality dimensions of participants who suffer from visual stress were compared with those of normal participants using the Eysenck Personality Inventory. Extraversion-Introversion scores showed no significant differences between the participants who suffered visual stress and those who were classified as normal. By contrast, significant differences were found between the normal participants and those with visual stress in respect of Neuroticism-Stability. These differences accord with Eysenck's personality theory which states that those who score highly on the neuroticism scale do so because they have a neurological system with a low threshold such that their neurological system is easily activated by external stimuli. The findings also relate directly to the theory of visual stress proposed by Wilkins which postulates that visual stress results from an excess of neural activity. The data may indicate that the excess activity is likely to be localised at particular neurological regions or neural processes.

Study on the echinococcosis blood serum detection based on Raman spectroscopy combined with neural network

NASA Astrophysics Data System (ADS)

Cheng, Jin-ying; Xu, Liang; Lü, Guo-dong; Tang, Jun; Mo, Jia-qing; Lü, Xiao-yi; Gao, Zhi-xian

2017-01-01

A Raman spectroscopy method combined with neural network is used for the invasive and rapid detection of echinococcosis. The Raman spectroscopy measurements are performed on two groups of blood serum samples, which are from 28 echinococcosis patients and 38 healthy persons, respectively. The normalized Raman reflection spectra show that the reflectivity of the echinococcosis blood serum is higher than that of the normal human blood serum in the wavelength ranges of 101—175 nm and 1 801—2 701 nm. Then the principal component analysis (PCA) and back propagation neural network (BPNN) model are used to obtain the diagnosis results. The diagnosis rates for healthy persons and echinococcosis persons are 93.333 3% and 90.909 1%, respectively, so the average final diagnosis rate is 92.121 2%. The results demonstrate that the Raman spectroscopy analysis of blood serum combined with PCA-BPNN has considerable potential for the non-invasive and rapid detection of echinococcosis.

Evaluation of Raman spectra of human brain tumor tissue using the learning vector quantization neural network

NASA Astrophysics Data System (ADS)

Liu, Tuo; Chen, Changshui; Shi, Xingzhe; Liu, Chengyong

2016-05-01

The Raman spectra of tissue of 20 brain tumor patients was recorded using a confocal microlaser Raman spectroscope with 785 nm excitation in vitro. A total of 133 spectra were investigated. Spectra peaks from normal white matter tissue and tumor tissue were analyzed. Algorithms, such as principal component analysis, linear discriminant analysis, and the support vector machine, are commonly used to analyze spectral data. However, in this study, we employed the learning vector quantization (LVQ) neural network, which is typically used for pattern recognition. By applying the proposed method, a normal diagnosis accuracy of 85.7% and a glioma diagnosis accuracy of 89.5% were achieved. The LVQ neural network is a recent approach to excavating Raman spectra information. Moreover, it is fast and convenient, does not require the spectra peak counterpart, and achieves a relatively high accuracy. It can be used in brain tumor prognostics and in helping to optimize the cutting margins of gliomas.

The neural network to determine the mechanical properties of the steels

NASA Astrophysics Data System (ADS)

Yemelyanov, Vitaliy; Yemelyanova, Nataliya; Safonova, Marina; Nedelkin, Aleksey

2018-04-01

The authors describe the neural network structure and software that is designed and developed to determine the mechanical properties of steels. The neural network is developed to refine upon the values of the steels properties. The results of simulations of the developed neural network are shown. The authors note the low standard error of the proposed neural network. To realize the proposed neural network the specialized software has been developed.

Detection and diagnosis of colitis on computed tomography using deep convolutional neural networks.

PubMed

Liu, Jiamin; Wang, David; Lu, Le; Wei, Zhuoshi; Kim, Lauren; Turkbey, Evrim B; Sahiner, Berkman; Petrick, Nicholas A; Summers, Ronald M

2017-09-01

Colitis refers to inflammation of the inner lining of the colon that is frequently associated with infection and allergic reactions. In this paper, we propose deep convolutional neural networks methods for lesion-level colitis detection and a support vector machine (SVM) classifier for patient-level colitis diagnosis on routine abdominal CT scans. The recently developed Faster Region-based Convolutional Neural Network (Faster RCNN) is utilized for lesion-level colitis detection. For each 2D slice, rectangular region proposals are generated by region proposal networks (RPN). Then, each region proposal is jointly classified and refined by a softmax classifier and bounding-box regressor. Two convolutional neural networks, eight layers of ZF net and 16 layers of VGG net are compared for colitis detection. Finally, for each patient, the detections on all 2D slices are collected and a SVM classifier is applied to develop a patient-level diagnosis. We trained and evaluated our method with 80 colitis patients and 80 normal cases using 4 × 4-fold cross validation. For lesion-level colitis detection, with ZF net, the mean of average precisions (mAP) were 48.7% and 50.9% for RCNN and Faster RCNN, respectively. The detection system achieved sensitivities of 51.4% and 54.0% at two false positives per patient for RCNN and Faster RCNN, respectively. With VGG net, Faster RCNN increased the mAP to 56.9% and increased the sensitivity to 58.4% at two false positive per patient. For patient-level colitis diagnosis, with ZF net, the average areas under the ROC curve (AUC) were 0.978 ± 0.009 and 0.984 ± 0.008 for RCNN and Faster RCNN method, respectively. The difference was not statistically significant with P = 0.18. At the optimal operating point, the RCNN method correctly identified 90.4% (72.3/80) of the colitis patients and 94.0% (75.2/80) of normal cases. The sensitivity improved to 91.6% (73.3/80) and the specificity improved to 95.0% (76.0/80) for the Faster RCNN method. With VGG net, Faster RCNN increased the AUC to 0.986 ± 0.007 and increased the diagnosis sensitivity to 93.7% (75.0/80) and specificity was unchanged at 95.0% (76.0/80). Colitis detection and diagnosis by deep convolutional neural networks is accurate and promising for future clinical application. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Early Binocular Input Is Critical for Development of Audiovisual but Not Visuotactile Simultaneity Perception.

PubMed

Chen, Yi-Chuan; Lewis, Terri L; Shore, David I; Maurer, Daphne

2017-02-20

Temporal simultaneity provides an essential cue for integrating multisensory signals into a unified perception. Early visual deprivation, in both animals and humans, leads to abnormal neural responses to audiovisual signals in subcortical and cortical areas [1-5]. Behavioral deficits in integrating complex audiovisual stimuli in humans are also observed [6, 7]. It remains unclear whether early visual deprivation affects visuotactile perception similarly to audiovisual perception and whether the consequences for either pairing differ after monocular versus binocular deprivation [8-11]. Here, we evaluated the impact of early visual deprivation on the perception of simultaneity for audiovisual and visuotactile stimuli in humans. We tested patients born with dense cataracts in one or both eyes that blocked all patterned visual input until the cataractous lenses were removed and the affected eyes fitted with compensatory contact lenses (mean duration of deprivation = 4.4 months; range = 0.3-28.8 months). Both monocularly and binocularly deprived patients demonstrated lower precision in judging audiovisual simultaneity. However, qualitatively different outcomes were observed for the two patient groups: the performance of monocularly deprived patients matched that of young children at immature stages, whereas that of binocularly deprived patients did not match any stage in typical development. Surprisingly, patients performed normally in judging visuotactile simultaneity after either monocular or binocular deprivation. Therefore, early binocular input is necessary to develop normal neural substrates for simultaneity perception of visual and auditory events but not visual and tactile events. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Lifespan Approach to Neuroinflammatory and Cognitive Disorders: A Critical Role for Glia

PubMed Central

Bilbo, Staci D.; Smith, Susan H.; Schwarz, Jaclyn M.

2011-01-01

Cognitive decline is a common problem of aging. Whereas multiple neural and glial mechanisms may account for these declines, microglial sensitization and/or dystrophy has emerged as a leading culprit in brain aging and dysfunction. However, glial activation is consistently observed in normal brain aging as well, independent of frank neuroinflammation or functional impairment. Such variability suggests the existence of additional vulnerability factors that can impact neuronal-glial interactions and thus overall brain and cognitive health. The goal of this review is to elucidate our working hypothesis that an individual‘s risk or resilience to neuroinflammatory disorders and poor cognitive aging may critically depend on their early life experience, which can change immune reactivity within the brain for the remainder of the lifespan. For instance, early-life infection in rats can profoundly disrupt memory function in young adulthood, as well as accelerate age-related cognitive decline, both of which are linked to enduring changes in glial function that occur in response to the initial infection. We discuss these findings within the context of the growing literature on the role of immune molecules and neuroimmune crosstalk in normal brain development. We highlight the intrinsic factors (e.g., chemokines, hormones) that regulate microglial development and their colonization of the embryonic and postnatal brain, and the capacity for disruption or “re-programming” of this crucial process by external events (e.g, stress, infection). An impact on glia, which in turn alters neural development, has the capacity to profoundly impact cognitive and mental health function at all stages of life. PMID:21822589

Disordered models of acquired dyslexia

NASA Astrophysics Data System (ADS)

Virasoro, M. A.

We show that certain specific correlations in the probability of errors observed in dyslexic patients that are normally explained by introducing additional complexity in the model for the reading process are typical of any Neural Network system that has learned to deal with a quasiregular environment. On the other hand we show that in Neural Networks the more regular behavior does not become naturally the default behavior.

Deep Convolutional Neural Networks for Endotracheal Tube Position and X-ray Image Classification: Challenges and Opportunities.

PubMed

Lakhani, Paras

2017-08-01

The goal of this study is to evaluate the efficacy of deep convolutional neural networks (DCNNs) in differentiating subtle, intermediate, and more obvious image differences in radiography. Three different datasets were created, which included presence/absence of the endotracheal (ET) tube (n = 300), low/normal position of the ET tube (n = 300), and chest/abdominal radiographs (n = 120). The datasets were split into training, validation, and test. Both untrained and pre-trained deep neural networks were employed, including AlexNet and GoogLeNet classifiers, using the Caffe framework. Data augmentation was performed for the presence/absence and low/normal ET tube datasets. Receiver operating characteristic (ROC), area under the curves (AUC), and 95% confidence intervals were calculated. Statistical differences of the AUCs were determined using a non-parametric approach. The pre-trained AlexNet and GoogLeNet classifiers had perfect accuracy (AUC 1.00) in differentiating chest vs. abdominal radiographs, using only 45 training cases. For more difficult datasets, including the presence/absence and low/normal position endotracheal tubes, more training cases, pre-trained networks, and data-augmentation approaches were helpful to increase accuracy. The best-performing network for classifying presence vs. absence of an ET tube was still very accurate with an AUC of 0.99. However, for the most difficult dataset, such as low vs. normal position of the endotracheal tube, DCNNs did not perform as well, but achieved a reasonable AUC of 0.81.

Invariant-feature-based adaptive automatic target recognition in obscured 3D point clouds

NASA Astrophysics Data System (ADS)

Khuon, Timothy; Kershner, Charles; Mattei, Enrico; Alverio, Arnel; Rand, Robert

2014-06-01

Target recognition and classification in a 3D point cloud is a non-trivial process due to the nature of the data collected from a sensor system. The signal can be corrupted by noise from the environment, electronic system, A/D converter, etc. Therefore, an adaptive system with a desired tolerance is required to perform classification and recognition optimally. The feature-based pattern recognition algorithm architecture as described below is particularly devised for solving a single-sensor classification non-parametrically. Feature set is extracted from an input point cloud, normalized, and classifier a neural network classifier. For instance, automatic target recognition in an urban area would require different feature sets from one in a dense foliage area. The figure above (see manuscript) illustrates the architecture of the feature based adaptive signature extraction of 3D point cloud including LIDAR, RADAR, and electro-optical data. This network takes a 3D cluster and classifies it into a specific class. The algorithm is a supervised and adaptive classifier with two modes: the training mode and the performing mode. For the training mode, a number of novel patterns are selected from actual or artificial data. A particular 3D cluster is input to the network as shown above for the decision class output. The network consists of three sequential functional modules. The first module is for feature extraction that extracts the input cluster into a set of singular value features or feature vector. Then the feature vector is input into the feature normalization module to normalize and balance it before being fed to the neural net classifier for the classification. The neural net can be trained by actual or artificial novel data until each trained output reaches the declared output within the defined tolerance. In case new novel data is added after the neural net has been learned, the training is then resumed until the neural net has incrementally learned with the new novel data. The associative memory capability of the neural net enables the incremental learning. The back propagation algorithm or support vector machine can be utilized for the classification and recognition.

Brain, body, and cognition: Neural, physiological and self-report correlates of phobic and normative fear

PubMed Central

Schaefer, Hillary S.; Larson, Christine L.; Davidson, Richard J.; Coan, James A.

2014-01-01

The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction. PMID:24561099

Adaptive template generation for amyloid PET using a deep learning approach.

PubMed

Kang, Seung Kwan; Seo, Seongho; Shin, Seong A; Byun, Min Soo; Lee, Dong Young; Kim, Yu Kyeong; Lee, Dong Soo; Lee, Jae Sung

2018-05-11

Accurate spatial normalization (SN) of amyloid positron emission tomography (PET) images for Alzheimer's disease assessment without coregistered anatomical magnetic resonance imaging (MRI) of the same individual is technically challenging. In this study, we applied deep neural networks to generate individually adaptive PET templates for robust and accurate SN of amyloid PET without using matched 3D MR images. Using 681 pairs of simultaneously acquired 11 C-PIB PET and T1-weighted 3D MRI scans of AD, MCI, and cognitively normal subjects, we trained and tested two deep neural networks [convolutional auto-encoder (CAE) and generative adversarial network (GAN)] that produce adaptive best PET templates. More specifically, the networks were trained using 685,100 pieces of augmented data generated by rotating 527 randomly selected datasets and validated using 154 datasets. The input to the supervised neural networks was the 3D PET volume in native space and the label was the spatially normalized 3D PET image using the transformation parameters obtained from MRI-based SN. The proposed deep learning approach significantly enhanced the quantitative accuracy of MRI-less amyloid PET assessment by reducing the SN error observed when an average amyloid PET template is used. Given an input image, the trained deep neural networks rapidly provide individually adaptive 3D PET templates without any discontinuity between the slices (in 0.02 s). As the proposed method does not require 3D MRI for the SN of PET images, it has great potential for use in routine analysis of amyloid PET images in clinical practice and research. © 2018 Wiley Periodicals, Inc.

Brain, body, and cognition: neural, physiological and self-report correlates of phobic and normative fear.

PubMed

Schaefer, Hillary S; Larson, Christine L; Davidson, Richard J; Coan, James A

2014-04-01

The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction. Copyright © 2014. Published by Elsevier B.V.

Alcohol and Drug Use and the Developing Brain

PubMed Central

Gray, Kevin M.

2016-01-01

Adolescence is an important neurodevelopmental period marked by rapidly escalating rates of alcohol and drug use. Over the past decade, research has attempted to disentangle pre- and post-substance use effects on brain development by using sophisticated longitudinal designs. This review focuses on recent, prospective studies and addresses the following important questions: (1) what neuropsychological and neural features predate adolescent substance use, making youth more vulnerable to engage in heavy alcohol or drug use, and (2) how does heavy alcohol and drug use affect normal neural development and cognitive functioning? Findings suggest that pre-existing neural features that relate to increased substance use during adolescence include poorer neuropsychological functioning on tests of inhibition and working memory, smaller gray and white matter volume, changes in white matter integrity, and altered brain activation during inhibition, working memory, reward, and resting state. After substance use is initiated, alcohol and marijuana use are associated with poorer cognitive functioning on tests of verbal memory, visuospatial functioning, psychomotor speed, working memory, attention, cognitive control, and overall IQ. Heavy alcohol use during adolescence is related to accelerated decreases in gray matter and attenuated increases in white matter volume, as well as increased brain activation during tasks of inhibition and working memory, relative to controls. Larger longitudinal studies with more diverse samples are needed to better understand the interactive effects of alcohol, marijuana, and other substances, as well as the role of sex, co-occurring psychopathology, genetics, sleep, and age of initiation on substance use. PMID:26984684

Effects of cordycepin on the microglia-overactivation-induced impairments of growth and development of hippocampal cultured neurons.

PubMed

Peng, Jie; Wang, Ping; Ge, Hongshan; Qu, Xianqin; Jin, Xingliang

2015-01-01

Microglial cells are normally activated in response to brain injury or immunological stimuli to protect central nervous system (CNS). However, over-activation of microglia conversely amplifies the inflammatory effects and mediates cellular degeneration, leading to the death of neurons. Recently, cordycepin, an active component found in Cordyceps militarisa known as a rare Chinese caterpillar fungus, has been reported as an effective drug for treating inflammatory diseases and cancer via unclear mechanisms. In this study, we attempted to identify the anti-inflammatory role of cordycepin and its protective effects on the impairments of neural growth and development induced by microglial over-activation. The results indicate that cordycepin could attenuate the lipopolysaccharide (LPS)-induced microglial activation, evidenced by the dramatically reduced release of TNF-α and IL-1β, as well as the down-regulation of mRNA levels of iNOS and COX-2 after cordycepin treatment. Besides, cordycepin reversed the LPS-induced activation of NF-κB pathway, resulting in anti-inflammatory effects. Furthermore, by employing the conditioned medium (CM), we found cordycepin was able to recover the impairments of neural growth and development in the primary hippocampal neurons cultured in LPS-CM, including cell viability, growth cone extension, neurite sprouting and outgrowth as well as spinogenesis. This study expands our knowledge of the anti-inflammatory function of cordycepin and paves the way for the biomedical applications of cordycepin in the therapies of neural injuries.

Neural and Muscular Contributions to the Age-Related Reductions in Rapid Strength.

PubMed

Gerstner, Gena R; Thompson, Brennan J; Rosenberg, Joseph G; Sobolewski, Eric J; Scharville, Michael J; Ryan, Eric D

2017-07-01

The purposes of this study were to investigate the age-related differences in absolute and normalized plantarflexion rate of torque development (RTD) at early (0-50 ms) and late (100-200 ms) time intervals and to examine specific neural and muscular mechanisms contributing to these differences. Thirty-two young (20.0 ± 2.1 yr) and 20 older (69.5 ± 3.3 yr) recreationally active men performed rapid plantarflexion isometric muscle actions to examine absolute and normalized RTD and muscle activation using EMG at early and late time intervals. Ultrasonography was used to examine medial gastrocnemius muscle size, echo intensity (EI), and muscle architecture (fascicle length [FL] and pennation angle [PA]). The older men were weaker (23.9%, P < 0.001) and had lower later absolute and normalized RTD (P = 0.001-0.034) variables when compared with the young men. The older men also had higher EI (P < 0.001), smaller PA (P = 0.004), and lower later EMG amplitude values (P = 0.009-0.046). However, there were no differences in early RTD and EMG amplitude values, muscle size, or FL between groups (P = 0.097-0.914). Lower late RTD values were related to higher EI, smaller PA, and lower EMG amplitude values (r = -0.28-0.59, P = 0.001-0.044); however, late RTD values were no longer related to PA after normalizing to peak torque. Age-related alterations in muscle quality (EI), architecture, and muscle activation may influence rapid torque production at late time intervals (≥100 ms) from contraction onset. These findings highlight specific neuromuscular factors that influence the age-related reductions in RTD, which has been shown to significantly influence function and performance in older adults.

Optical biopsy of head and neck cancer using hyperspectral imaging and convolutional neural networks

NASA Astrophysics Data System (ADS)

Halicek, Martin; Little, James V.; Wang, Xu; Patel, Mihir; Griffith, Christopher C.; El-Deiry, Mark W.; Chen, Amy Y.; Fei, Baowei

2018-02-01

Successful outcomes of surgical cancer resection necessitate negative, cancer-free surgical margins. Currently, tissue samples are sent to pathology for diagnostic confirmation. Hyperspectral imaging (HSI) is an emerging, non-contact optical imaging technique. A reliable optical method could serve to diagnose and biopsy specimens in real-time. Using convolutional neural networks (CNNs) as a tissue classifier, we developed a method to use HSI to perform an optical biopsy of ex-vivo surgical specimens, collected from 21 patients undergoing surgical cancer resection. Training and testing on samples from different patients, the CNN can distinguish squamous cell carcinoma (SCCa) from normal aerodigestive tract tissues with an area under the curve (AUC) of 0.82, 81% accuracy, 81% sensitivity, and 80% specificity. Additionally, normal oral tissues can be sub-classified into epithelium, muscle, and glandular mucosa using a decision tree method, with an average AUC of 0.94, 90% accuracy, 93% sensitivity, and 89% specificity. After separately training on thyroid tissue, the CNN differentiates between thyroid carcinoma and normal thyroid with an AUC of 0.95, 92% accuracy, 92% sensitivity, and 92% specificity. Moreover, the CNN can discriminate medullary thyroid carcinoma from benign multi-nodular goiter (MNG) with an AUC of 0.93, 87% accuracy, 88% sensitivity, and 85% specificity. Classical-type papillary thyroid carcinoma is differentiated from benign MNG with an AUC of 0.91, 86% accuracy, 86% sensitivity, and 86% specificity. Our preliminary results demonstrate that an HSI-based optical biopsy method using CNNs can provide multi-category diagnostic information for normal head-and-neck tissue, SCCa, and thyroid carcinomas. More patient data are needed in order to fully investigate the proposed technique to establish reliability and generalizability of the work.

A PML/Slit Axis Controls Physiological Cell Migration and Cancer Invasion in the CNS.

PubMed

Amodeo, Valeria; A, Deli; Betts, Joanne; Bartesaghi, Stefano; Zhang, Ying; Richard-Londt, Angela; Ellis, Matthew; Roshani, Rozita; Vouri, Mikaella; Galavotti, Sara; Oberndorfer, Sarah; Leite, Ana Paula; Mackay, Alan; Lampada, Aikaterini; Stratford, Eva Wessel; Li, Ningning; Dinsdale, David; Grimwade, David; Jones, Chris; Nicotera, Pierluigi; Michod, David; Brandner, Sebastian; Salomoni, Paolo

2017-07-11

Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/stem cell (NPC) and neuroblast migration in the adult mouse brain. The PML pro-migratory role is active also in transformed mouse NPCs and in human primary GBM cells. In both normal and neoplastic settings, PML controls cell migration via Polycomb repressive complex 2 (PRC2)-mediated repression of Slits, key regulators of axon guidance. Finally, a PML/SLIT1 axis regulates sensitivity to the PML-targeting drug arsenic trioxide in primary GBM cells. Taken together, these findings uncover a drug-targetable molecular axis controlling cell migration in both normal and neoplastic cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Application of a neural network to simulate analysis in an optimization process

NASA Technical Reports Server (NTRS)

Rogers, James L.; Lamarsh, William J., II

1992-01-01

A new experimental software package called NETS/PROSSS aimed at reducing the computing time required to solve a complex design problem is described. The software combines a neural network for simulating the analysis program with an optimization program. The neural network is applied to approximate results of a finite element analysis program to quickly obtain a near-optimal solution. Results of the NETS/PROSSS optimization process can also be used as an initial design in a normal optimization process and make it possible to converge to an optimum solution with significantly fewer iterations.

A Prior for Neural Networks utilizing Enclosing Spheres for Normalization

NASA Astrophysics Data System (ADS)

v. Toussaint, U.; Gori, S.; Dose, V.

2004-11-01

Neural Networks are famous for their advantageous flexibility for problems when there is insufficient knowledge to set up a proper model. On the other hand this flexibility can cause over-fitting and can hamper the generalization properties of neural networks. Many approaches to regularize NN have been suggested but most of them based on ad-hoc arguments. Employing the principle of transformation invariance we derive a general prior in accordance with the Bayesian probability theory for a class of feedforward networks. Optimal networks are determined by Bayesian model comparison verifying the applicability of this approach.

Differences in neural activation between preterm and full term born adolescents on a sentence comprehension task: implications for educational accommodations.

PubMed

Barde, Laura H F; Yeatman, Jason D; Lee, Eliana S; Glover, Gary; Feldman, Heidi M

2012-02-15

Adolescent survivors of preterm birth experience persistent functional problems that negatively impact academic outcomes, even when standardized measures of cognition and language suggest normal ability. In this fMRI study, we compared the neural activation supporting auditory sentence comprehension in two groups of adolescents (ages 9-16 years); sentences varied in length and syntactic difficulty. Preterms (n=18, mean gestational age 28.8 weeks) and full terms (n=14) had scores on verbal IQ, receptive vocabulary, and receptive language tests that were within or above normal limits and similar between groups. In early and late phases of the trial, we found interactions by group and length; in the late phase, we also found a group by syntactic difficulty interaction. Post hoc tests revealed that preterms demonstrated significant activation in the left and right middle frontal gyri as syntactic difficulty increased. ANCOVA showed that the interactions could not be attributed to differences in age, receptive language skill, or reaction time. Results are consistent with the hypothesis that preterm birth modulates brain-behavior relations in sentence comprehension as task demands increase. We suggest preterms' differences in neural processing may indicate a need for educational accommodations, even when formal test scores indicate normal academic achievement. Copyright © 2011 Elsevier Ltd. All rights reserved.

Using Neural Networks to Describe Tracer Correlations

NASA Technical Reports Server (NTRS)

Lary, D. J.; Mueller, M. D.; Mussa, H. Y.

2003-01-01

Neural networks are ideally suited to describe the spatial and temporal dependence of tracer-tracer correlations. The neural network performs well even in regions where the correlations are less compact and normally a family of correlation curves would be required. For example, the CH4-N2O correlation can be well described using a neural network trained with the latitude, pressure, time of year, and CH4 volume mixing ratio (v.m.r.). In this study a neural network using Quickprop learning and one hidden layer with eight nodes was able to reproduce the CH4-N2O correlation with a correlation co- efficient of 0.9995. Such an accurate representation of tracer-tracer correlations allows more use to be made of long-term datasets to constrain chemical models. Such as the dataset from the Halogen Occultation Experiment (HALOE) which has continuously observed CH4, (but not N2O) from 1991 till the present. The neural network Fortran code used is available for download.

Method of gear fault diagnosis based on EEMD and improved Elman neural network

NASA Astrophysics Data System (ADS)

Zhang, Qi; Zhao, Wei; Xiao, Shungen; Song, Mengmeng

2017-05-01

Aiming at crack and wear and so on of gears Fault information is difficult to diagnose usually due to its weak, a gear fault diagnosis method that is based on EEMD and improved Elman neural network fusion is proposed. A number of IMF components are obtained by decomposing denoised all kinds of fault signals with EEMD, and the pseudo IMF components is eliminated by using the correlation coefficient method to obtain the effective IMF component. The energy characteristic value of each effective component is calculated as the input feature quantity of Elman neural network, and the improved Elman neural network is based on standard network by adding a feedback factor. The fault data of normal gear, broken teeth, cracked gear and attrited gear were collected by field collecting. The results were analyzed by the diagnostic method proposed in this paper. The results show that compared with the standard Elman neural network, Improved Elman neural network has the advantages of high diagnostic efficiency.

Physiologic Inter-eye Differences in Monkey Optic Nerve Head Architecture and Their Relation to Changes in Early Experimental Glaucoma

PubMed Central

Yang, Hongli; Downs, J. Crawford; Burgoyne, Claude F.

2009-01-01

Purpose To characterize physiologic inter-eye differences in optic nerve head (ONH) architecture within six normal rhesus monkeys and compare them to inter-eye differences within three previously-reported cynomolgus monkeys with early experimental glaucoma (EEG). Methods Trephinated ONH and peripapillary sclera from both eyes of six normal monkeys were serial sectioned, 3D reconstructed, 3D delineated and parameterized. For each normal animal, and each parameter, physiologic inter-eye difference (PID) was calculated (both overall and regionally) by converting all OS data to OD configuration and subtracting the OS from the OD value and Physiologic Inter-eye Percent Difference (PIPD) was calculated as the PID divided by the measurement mean of the two eyes. For each EEG monkey, inter-eye (EEG minus normal) differences and percent differences for each parameter overall and regionally were compared to the PID and PIPD Maximums. Results For all parameters the PID Maximums were relatively small overall. Compared to overall PID maximums, overall inter-eye differences in EEG monkeys were greatest for laminar deformation and thickening, posterior scleral canal enlargement, cupping and prelaminar neural tissue thickening. Compared to the regional PID Maximums, the lamina cribrosa was posteriorly deformed centrally, inferiorly, inferonasally and superiorly and was thickened centrally. The prelaminar neural tissues were thickened inferiorly, inferonasally and superiorly. Conclusion These data provide the first characterization of PID/PIPD maximums for ONH neural and connective tissue parameters in normal monkeys and serve to further clarify the location and character of early ONH change in experimental glaucoma. However, because of the species differences, the findings in EEG need to be confirmed within EEG rhesus monkey eyes. PMID:18775866

Application of structured support vector machine backpropagation to a convolutional neural network for human pose estimation.

PubMed

Witoonchart, Peerajak; Chongstitvatana, Prabhas

2017-08-01

In this study, for the first time, we show how to formulate a structured support vector machine (SSVM) as two layers in a convolutional neural network, where the top layer is a loss augmented inference layer and the bottom layer is the normal convolutional layer. We show that a deformable part model can be learned with the proposed structured SVM neural network by backpropagating the error of the deformable part model to the convolutional neural network. The forward propagation calculates the loss augmented inference and the backpropagation calculates the gradient from the loss augmented inference layer to the convolutional layer. Thus, we obtain a new type of convolutional neural network called an Structured SVM convolutional neural network, which we applied to the human pose estimation problem. This new neural network can be used as the final layers in deep learning. Our method jointly learns the structural model parameters and the appearance model parameters. We implemented our method as a new layer in the existing Caffe library. Copyright © 2017 Elsevier Ltd. All rights reserved.

Estimation of Muscle Force Based on Neural Drive in a Hemispheric Stroke Survivor.

PubMed

Dai, Chenyun; Zheng, Yang; Hu, Xiaogang

2018-01-01

Robotic assistant-based therapy holds great promise to improve the functional recovery of stroke survivors. Numerous neural-machine interface techniques have been used to decode the intended movement to control robotic systems for rehabilitation therapies. In this case report, we tested the feasibility of estimating finger extensor muscle forces of a stroke survivor, based on the decoded descending neural drive through population motoneuron discharge timings. Motoneuron discharge events were obtained by decomposing high-density surface electromyogram (sEMG) signals of the finger extensor muscle. The neural drive was extracted from the normalized frequency of the composite discharge of the motoneuron pool. The neural-drive-based estimation was also compared with the classic myoelectric-based estimation. Our results showed that the neural-drive-based approach can better predict the force output, quantified by lower estimation errors and higher correlations with the muscle force, compared with the myoelectric-based estimation. Our findings suggest that the neural-drive-based approach can potentially be used as a more robust interface signal for robotic therapies during the stroke rehabilitation.

The Laplacian spectrum of neural networks

PubMed Central

de Lange, Siemon C.; de Reus, Marcel A.; van den Heuvel, Martijn P.

2014-01-01

The brain is a complex network of neural interactions, both at the microscopic and macroscopic level. Graph theory is well suited to examine the global network architecture of these neural networks. Many popular graph metrics, however, encode average properties of individual network elements. Complementing these “conventional” graph metrics, the eigenvalue spectrum of the normalized Laplacian describes a network's structure directly at a systems level, without referring to individual nodes or connections. In this paper, the Laplacian spectra of the macroscopic anatomical neuronal networks of the macaque and cat, and the microscopic network of the Caenorhabditis elegans were examined. Consistent with conventional graph metrics, analysis of the Laplacian spectra revealed an integrative community structure in neural brain networks. Extending previous findings of overlap of network attributes across species, similarity of the Laplacian spectra across the cat, macaque and C. elegans neural networks suggests a certain level of consistency in the overall architecture of the anatomical neural networks of these species. Our results further suggest a specific network class for neural networks, distinct from conceptual small-world and scale-free models as well as several empirical networks. PMID:24454286

Using an Extended Kalman Filter Learning Algorithm for Feed-Forward Neural Networks to Describe Tracer Correlations

NASA Technical Reports Server (NTRS)

Lary, David J.; Mussa, Yussuf

2004-01-01

In this study a new extended Kalman filter (EKF) learning algorithm for feed-forward neural networks (FFN) is used. With the EKF approach, the training of the FFN can be seen as state estimation for a non-linear stationary process. The EKF method gives excellent convergence performances provided that there is enough computer core memory and that the machine precision is high. Neural networks are ideally suited to describe the spatial and temporal dependence of tracer-tracer correlations. The neural network performs well even in regions where the correlations are less compact and normally a family of correlation curves would be required. For example, the CH4-N2O correlation can be well described using a neural network trained with the latitude, pressure, time of year, and CH4 volume mixing ratio (v.m.r.). The neural network was able to reproduce the CH4-N2O correlation with a correlation coefficient between simulated and training values of 0.9997. The neural network Fortran code used is available for download.

A novel material screening platform for nanoporous gold-based neural electrodes

NASA Astrophysics Data System (ADS)

Chapman, Christopher Abbott Reece

Neural-electrical interfaces have emerged in the past decades as a promising modality to facilitate the understanding of the electropathophysiology of neurological disorders as well as the normal functioning of the central nervous system, and enable the treatment of neurological defects through electrical stimulation or electrically-controlled drug delivery. However, chronically implanted electrodes face a myriad of design challenges, including their coupling to neural tissue (biocompatibility), small form factor requirement, and their electrical properties (maintaining a low electrical impedance). Planar electrode materials such as planar platinum and gold experience a large increase in electrical impedance when electrode dimensions are reduced to increase spatial resolution of neural recordings. A decrease in electrode surface area reduces the total capacitance of the electrode double layer resulting in an increase in electrode impedance. This high impedance can reduce the signal amplitude and increase the thermal noise, resulting in degradation of signal-to-noise ratio. Conventionally, this increase in electrical impedance at small electrode dimensions has been mitigated by coatings with rough morphologies such as platinum black, conducting polymers, and titanium nitride. Porous surfaces have high effective surface area enabling low impedance at small electrode dimensions. However, achieving long-term stability of cellular coupling to the electrode surface has remained difficult. Designing electrodes that can physically couple with neurons successfully and maintain low impedance at small electrode dimensions necessitates consideration of novel electrode coatings, such as carbon nanotubes and gold nanopillars. Another promising material, and focus of this proposal, is thin film nanoporous gold (np-Au). Nanoporous gold is a promising material for addressing these limitations because of its inherently large effective surface area allows for lower impedances at small form factors, and its modifiable surface morphology can be used to control cell-electrode coupling. Additionally, thin film nanoporous gold is fabricated by traditional microfabrication methods, and thus can be directly adopted by the current state-of-the-art neural electrode fabrication processes. All these properties make thin film nanoporous gold a promising candidate for use in neural electrode surfaces. This dissertation seeks to characterize both the morphological and the electrical response of neural cells to thin film nanoporous gold morphologies using an in vitro electrode morphology screening platform. The specific aims for this proposal are to: (i) develop a electrode morphology library that displays varying topographies to study structure-property relationships of thin film nanoporous gold and cellular response, (ii) characterize neural cell response to identified nanoporous gold topographies that reduce adverse tissue response in vitro, and (iii) develop an electrophysiology platform to characterize neural coupling to each identified nanoporous gold topography.

Stability switches and multistability coexistence in a delay-coupled neural oscillators system.

PubMed

Song, Zigen; Xu, Jian

2012-11-21

In this paper, we present a neural network system composed of two delay-coupled neural oscillators, where each of these can be regarded as the dynamical system describing the average activity of neural population. Analyzing the corresponding characteristic equation, the local stability of rest state is studied. The system exhibits the switch phenomenon between the rest state and periodic activity. Furthermore, the Hopf bifurcation is analyzed and the bifurcation curve is given in the parameters plane. The stability of the bifurcating periodic solutions and direction of the Hopf bifurcation are exhibited. Regarding time delay and coupled weight as the bifurcation parameters, the Fold-Hopf bifurcation is investigated in detail in terms of the central manifold reduction and normal form method. The neural system demonstrates the coexistence of the rest states and periodic activities in the different parameter regions. Employing the normal form of the original system, the coexistence regions are illustrated approximately near the Fold-Hopf singularity point. Finally, numerical simulations are performed to display more complex dynamics. The results illustrate that system may exhibit the rich coexistence of the different neuro-computational properties, such as the rest states, periodic activities, and quasi-periodic behavior. In particular, some periodic activities can evolve into the bursting-type behaviors with the varying time delay. It implies that the coexistence of the quasi-periodic activity and bursting-type behavior can be obtained if the suitable value of system parameter is chosen. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cancer diagnostics using neural network sorting of processed images

NASA Astrophysics Data System (ADS)

Wyman, Charles L.; Schreeder, Marshall; Grundy, Walt; Kinser, Jason M.

1996-03-01

A combination of image processing with neural network sorting was conducted to demonstrate feasibility of automated cervical smear screening. Nuclei were isolated to generate a series of data points relating to the density and size of individual nuclei. This was followed by segmentation to isolate entire cells for subsequent generation of data points to bound the size of the cytoplasm. Data points were taken on as many as ten cells per image frame and included correlation against a series of filters providing size and density readings on nuclei. Additional point data was taken on nuclei images to refine size information and on whole cells to bound the size of the cytoplasm, twenty data points per assessed cell were generated. These data point sets, designated as neural tensors, comprise the inputs for training and use of a unique neural network to sort the images and identify those indicating evidence of disease. The neural network, named the Fast Analog Associative Memory, accumulates data and establishes lookup tables for comparison against images to be assessed. Six networks were trained to differentiate normal cells from those evidencing various levels abnormality that may lead to cancer. A blind test was conducted on 77 images to evaluate system performance. The image set included 31 positives (diseased) and 46 negatives (normal). Our system correctly identified all 31 positives and 41 of the negatives with 5 false positives. We believe this technology can lead to more efficient automated screening of cervical smears.

Melanoma segmentation based on deep learning.

PubMed

Zhang, Xiaoqing

2017-12-01

Malignant melanoma is one of the most deadly forms of skin cancer, which is one of the world's fastest-growing cancers. Early diagnosis and treatment is critical. In this study, a neural network structure is utilized to construct a broad and accurate basis for the diagnosis of skin cancer, thereby reducing screening errors. The technique is able to improve the efficacy for identification of normally indistinguishable lesions (such as pigment spots) versus clinically unknown lesions, and to ultimately improve the diagnostic accuracy. In the field of medical imaging, in general, using neural networks for image segmentation is relatively rare. The existing traditional machine-learning neural network algorithms still cannot completely solve the problem of information loss, nor detect the precise division of the boundary area. We use an improved neural network framework, described herein, to achieve efficacious feature learning, and satisfactory segmentation of melanoma images. The architecture of the network includes multiple convolution layers, dropout layers, softmax layers, multiple filters, and activation functions. The number of data sets can be increased via rotation of the training set. A non-linear activation function (such as ReLU and ELU) is employed to alleviate the problem of gradient disappearance, and RMSprop/Adam are incorporated to optimize the loss algorithm. A batch normalization layer is added between the convolution layer and the activation layer to solve the problem of gradient disappearance and explosion. Experiments, described herein, show that our improved neural network architecture achieves higher accuracy for segmentation of melanoma images as compared with existing processes.

Structural reliability calculation method based on the dual neural network and direct integration method.

PubMed

Li, Haibin; He, Yun; Nie, Xiaobo

2018-01-01

Structural reliability analysis under uncertainty is paid wide attention by engineers and scholars due to reflecting the structural characteristics and the bearing actual situation. The direct integration method, started from the definition of reliability theory, is easy to be understood, but there are still mathematics difficulties in the calculation of multiple integrals. Therefore, a dual neural network method is proposed for calculating multiple integrals in this paper. Dual neural network consists of two neural networks. The neural network A is used to learn the integrand function, and the neural network B is used to simulate the original function. According to the derivative relationships between the network output and the network input, the neural network B is derived from the neural network A. On this basis, the performance function of normalization is employed in the proposed method to overcome the difficulty of multiple integrations and to improve the accuracy for reliability calculations. The comparisons between the proposed method and Monte Carlo simulation method, Hasofer-Lind method, the mean value first-order second moment method have demonstrated that the proposed method is an efficient and accurate reliability method for structural reliability problems.

DUF1220 protein domains drive proliferation in human neural stem cells and are associated with increased cortical volume in anthropoid primates.

PubMed

Keeney, J G; Davis, J M; Siegenthaler, J; Post, M D; Nielsen, B S; Hopkins, W D; Sikela, J M

2015-09-01

Genome sequences encoding DUF1220 protein domains show a burst in copy number among anthropoid species and especially humans, where they have undergone the greatest human lineage-specific copy number expansion of any protein coding sequence in the genome. While DUF1220 copy number shows a dosage-related association with brain size in both normal populations and in 1q21.1-associated microcephaly and macrocephaly, a function for these domains has not yet been described. Here we provide multiple lines of evidence supporting the view that DUF1220 domains function as drivers of neural stem cell proliferation among anthropoid species including humans. First, we show that brain MRI data from 131 individuals across 7 anthropoid species shows a strong correlation between DUF1220 copy number and multiple brain size-related measures. Using in situ hybridization analyses of human fetal brain, we also show that DUF1220 domains are expressed in the ventricular zone and primarily during human cortical neurogenesis, and are therefore expressed at the right time and place to be affecting cortical brain development. Finally, we demonstrate that in vitro expression of DUF1220 sequences in neural stem cells strongly promotes proliferation. Taken together, these data provide the strongest evidence so far reported implicating DUF1220 dosage in anthropoid and human brain expansion through mechanisms involving increasing neural stem cell proliferation.

Neural dissociation of food- and money-related reward processing using an abstract incentive delay task.

PubMed

Simon, Joe J; Skunde, Mandy; Wu, Mudan; Schnell, Knut; Herpertz, Sabine C; Bendszus, Martin; Herzog, Wolfgang; Friederich, Hans-Christoph

2015-08-01

Food is an innate reward stimulus related to energy homeostasis and survival, whereas money is considered a more general reward stimulus that gains a rewarding value through learning experiences. Although the underlying neural processing for both modalities of reward has been investigated independently from one another, a more detailed investigation of neural similarities and/or differences between food and monetary reward is still missing. Here, we investigated the neural processing of food compared with monetary-related rewards in 27 healthy, normal-weight women using functional magnetic resonance imaging. We developed a task distinguishing between the anticipation and the receipt of either abstract food or monetary reward. Both tasks activated the ventral striatum during the expectation of a reward. Compared with money, greater food-related activations were observed in prefrontal, parietal and central midline structures during the anticipation and lateral orbitofrontal cortex (lOFC) during the receipt of food reward. Furthermore, during the receipt of food reward, brain activation in the secondary taste cortex was positively related to the body mass index. These results indicate that food-dependent activations encompass to a greater extent brain regions involved in self-control and self-reflection during the anticipation and phylogenetically older parts of the lOFC during the receipt of reward. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Neural stem cell proliferation and differentiation in the conductive PEDOT-HA/Cs/Gel scaffold for neural tissue engineering.

PubMed

Wang, Shuping; Guan, Shui; Xu, Jianqiang; Li, Wenfang; Ge, Dan; Sun, Changkai; Liu, Tianqing; Ma, Xuehu

2017-09-26

Engineering scaffolds with excellent electro-activity is increasingly important in tissue engineering and regenerative medicine. Herein, conductive poly(3,4-ethylenedioxythiophene) doped with hyaluronic acid (PEDOT-HA) nanoparticles were firstly synthesized via chemical oxidant polymerization. A three-dimensional (3D) PEDOT-HA/Cs/Gel scaffold was then developed by introducing PEDOT-HA nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. HA, as a bridge, not only was used as a dopant, but also combined PEDOT into the Cs/Gel via chemical crosslinking. The PEDOT-HA/Cs/Gel scaffold was used as a conductive substrate for neural stem cell (NSC) culture in vitro. The results demonstrated that the PEDOT-HA/Cs/Gel scaffold had excellent biocompatibility for NSC proliferation and differentiation. 3D confocal fluorescence images showed cells attached on the channel surface of Cs/Gel and PEDOT-HA/Cs/Gel scaffolds with a normal neuronal morphology. Compared to the Cs/Gel scaffold, the PEDOT-HA/Cs/Gel scaffold not only promoted NSC proliferation with up-regulated expression of Ki67, but also enhanced NSC differentiation into neurons and astrocytes with up-regulated expression of β tubulin-III and GFAP, respectively. It is expected that this electro-active and bio-active PEDOT-HA/Cs/Gel scaffold will be used as a conductive platform to regulate NSC behavior for neural tissue engineering.

Spatial-anatomical mapping of NoGo-P3 in the offspring of alcoholics: Evidence of cognitive and neural disinhibition as a risk for alcoholism

PubMed Central

Kamarajan, Chella; Porjesz, Bernice; Jones, Kevin A.; Chorlian, David B.; Padmanabhapillai, Ajayan; Rangaswamy, Madhavi; Stimus, Arthur T.; Begleiter, Henri

2013-01-01

Objective The concept of disinhibition as a behavioral and biological trait has been considered to be involved in the etiology of alcoholism and its co-existing disorders. The magnitude and functional mapping of event-related potential P3(00) components were analyzed, in order to examine the possible response inhibition deficits in the offspring of alcoholics. Method The P3 components were compared between 50 offspring of alcoholics (OA) and a matched normal control group (NC) using a visual Go/NoGo task. The low-resolution electromagnetic tomography (LORETA) was used to analyze the functional brain mapping between groups. Results The results indicated that the OA group manifested decreased P3 amplitude during the NoGo but not the Go condition compared to the NC group. The voxel-by-voxel analysis in LORETA showed group differences at several brain regions including prefrontal areas during the processing of NoGo but not Go signals. Conclusions The decreased NoGo-P3 suggests that cognitive and neural disinhibition in offspring of alcoholics may serve as a neurocognitive index for a phenotypic marker in the development of alcoholism and related disorders. Significance Dysfunctional neural and response inhibition in the offspring of alcoholics perhaps provides an endophenotypic marker of risk for the development of alcoholism and related disorders. PMID:15826845

Metabolic and vascular origins of the BOLD effect: Implications for imaging pathology and resting-state brain function.

PubMed

Mark, Clarisse I; Mazerolle, Erin L; Chen, J Jean

2015-08-01

The blood oxygenation level-dependent (BOLD) phenomenon has profoundly revolutionized neuroscience, with applications ranging from normal brain development and aging, to brain disorders and diseases. While the BOLD effect represents an invaluable tool to map brain function, it does not measure neural activity directly; rather, it reflects changes in blood oxygenation resulting from the relative balance between cerebral oxygen metabolism (through neural activity) and oxygen supply (through cerebral blood flow and volume). As such, there are cases in which BOLD signals might be dissociated from neural activity, leading to misleading results. The emphasis of this review is to develop a critical perspective for interpreting BOLD results, through a comprehensive consideration of BOLD's metabolic and vascular underpinnings. We demonstrate that such an understanding is especially important under disease or resting conditions. We also describe state-of-the-art acquisition and analytical techniques to reveal physiological information on the mechanisms underlying measured BOLD signals. With these goals in mind, this review is structured to provide a fundamental understanding of: 1) the physiological and physical sources of the BOLD contrast; 2) the extraction of information regarding oxidative metabolism and cerebrovascular reactivity from the BOLD signal, critical to investigating neuropathology; and 3) the fundamental importance of metabolic and vascular mechanisms for interpreting resting-state BOLD measurements. © 2015 Wiley Periodicals, Inc.

Vasopressin differentially modulates aggression and anxiety in adolescent hamsters administered anabolic steroids.

PubMed

Morrison, Thomas R; Ricci, Lesley A; Melloni, Richard H

2016-11-01

Adolescent Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids display increased offensive aggression and decreased anxiety correlated with an increase in vasopressin afferent development, synthesis, and neural signaling within the anterior hypothalamus. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts as hamsters display decreased offensive aggression and increased anxiety correlated with a decrease in anterior hypothalamic vasopressin. This study investigated the hypothesis that alterations in anterior hypothalamic vasopressin neural signaling modulate behavioral shifting between adolescent anabolic/androgenic steroid-induced offensive aggression and anxiety. To test this, adolescent male hamsters were administered anabolic/androgenic steroids and tested for offensive aggression or anxiety following direct pharmacological manipulation of vasopressin V1A receptor signaling within the anterior hypothalamus. Blockade of anterior hypothalamic vasopressin V1A receptor signaling suppressed offensive aggression and enhanced general and social anxiety in hamsters administered anabolic/androgenic steroids during adolescence, effectively reversing the pattern of behavioral response pattern normally observed during the adolescent exposure period. Conversely, activation of anterior hypothalamic vasopressin V1A receptor signaling enhanced offensive aggression in hamsters exposed to anabolic/androgenic steroids during adolescence. Together, these findings suggest that the state of vasopressin neural development and signaling in the anterior hypothalamus plays an important role in behavioral shifting between aggression and anxiety following adolescent exposure to anabolic/androgenic steroids. Copyright © 2016 Elsevier Inc. All rights reserved.

Vasopressin Differentially Modulates Aggression and Anxiety in Adolescent Hamsters Administered Anabolic Steroids

PubMed Central

Morrison, Thomas R.; Ricci, Lesley A.; Melloni, Richard H.

2016-01-01

Adolescent Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids display increased offensive aggression and decreased anxiety correlated with an increase in vasopressin afferent development, synthesis, and neural signaling within the anterior hypothalamus. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts as hamsters display decreased offensive aggression and increased anxiety correlated with a decrease in anterior hypothalamic vasopressin. This study investigated the hypothesis that alterations in anterior hypothalamic vasopressin neural signaling modulate behavioral shifting between adolescent anabolic/androgenic steroid-induced offensive aggression and anxiety. To test this, adolescent male hamsters were administered anabolic/androgenic steroids and tested for offensive aggression or anxiety following direct pharmacological manipulation of vasopressin V1A receptor signaling within the anterior hypothalamus. Blockade of anterior hypothalamic vasopressin V1A receptor signaling suppressed offensive aggression and enhanced general and social anxiety in hamsters administered anabolic/androgenic steroids during adolescence, effectively reversing the pattern of behavioral response pattern normally observed during the adolescent exposure period. Conversely, activation of anterior hypothalamic vasopressin V1A receptor signaling enhanced offensive aggression in hamsters exposed to anabolic/androgenic steroids during adolescence. Together, these findings suggest that the state of vasopressin neural development and signaling in the anterior hypothalamus plays an important role in behavioral shifting between aggression and anxiety following adolescent exposure to anabolic/androgenic steroids. PMID:27149949

The Neural Cell Adhesion Molecule-Derived Peptide FGL Facilitates Long-Term Plasticity in the Dentate Gyrus in Vivo

ERIC Educational Resources Information Center

Dallerac, Glenn; Zerwas, Meike; Novikova, Tatiana; Callu, Delphine; Leblanc-Veyrac, Pascale; Bock, Elisabeth; Berezin, Vladimir; Rampon, Claire; Doyere, Valerie

2011-01-01

The neural cell adhesion molecule (NCAM) is known to play a role in developmental and structural processes but also in synaptic plasticity and memory of the adult animal. Recently, FGL, a NCAM mimetic peptide that binds to the Fibroblast Growth Factor Receptor 1 (FGFR-1), has been shown to have a beneficial impact on normal memory functioning, as…

Excitatory, inhibitory and facilitatory frequency response areas in the inferior colliculus of hearing impaired mice.

PubMed

Felix, Richard A; Portfors, Christine V

2007-06-01

Individuals with age-related hearing loss often have difficulty understanding complex sounds such as basic speech. The C57BL/6 mouse suffers from progressive sensorineural hearing loss and thus is an effective tool for dissecting the neural mechanisms underlying changes in complex sound processing observed in humans. Neural mechanisms important for processing complex sounds include multiple tuning and combination sensitivity, and these responses are common in the inferior colliculus (IC) of normal hearing mice. We examined neural responses in the IC of C57Bl/6 mice to single and combinations of tones to examine the extent of spectral integration in the IC after age-related high frequency hearing loss. Ten percent of the neurons were tuned to multiple frequency bands and an additional 10% displayed non-linear facilitation to the combination of two different tones (combination sensitivity). No combination-sensitive inhibition was observed. By comparing these findings to spectral integration properties in the IC of normal hearing CBA/CaJ mice, we suggest that high frequency hearing loss affects some of the neural mechanisms in the IC that underlie the processing of complex sounds. The loss of spectral integration properties in the IC during aging likely impairs the central auditory system's ability to process complex sounds such as speech.

Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

PubMed

Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

2017-01-01

Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Transgenic mice overexpressing the extracellular domain of NCAM are impaired in working memory and cortical plasticity

PubMed Central

Brennaman, Leann H.; Kochlamazashvili, Gaga; Stoenica, Luminita; Nonneman, Randall J.; Moy, Sheryl S.; Schachner, Melitta; Dityatev, Alexander; Maness, Patricia F.

2011-01-01

The neural cell adhesion molecule, NCAM, is a pivotal regulator of neural development, with key roles in axonal and dendritic growth and synaptic plasticity. Alterations in NCAM expression or proteolytic cleavage have been linked to human neuropsychiatric disorders such as schizophrenia, bipolar disorder and Alzheimer’s disease, and may contribute to cognitive dysfunction. We have generated mice overexpressing the NCAM extracellular (EC) proteolytic cleavage fragment which has been reported to be increased in schizophrenic versus normal brains. These mice show impaired GABAergic innervation and reduced number of apical dendritic spines on pyramidal neurons in the prefrontal cortex (PFC). Here, these NCAM-EC transgenic mice were subjected to behavioral tasks and electrophysiological measurements to determine the impact of structural abnormalities in the PFC on synaptic and cognitive functions. NCAM-EC mice exhibited impaired working memory in a delayed non-match-to-sample task, which requires PFC function, but showed no differences in anxiety, olfactory abilities, or sociability. Transgenic mice displayed impaired long- and short-term potentiation in the PFC but normal synaptic plasticity in the hippocampus, suggesting that the abnormal synaptic innervation in NCAM-EC mice impairs PFC plasticity and alters working memory. These findings may have implications for cognitive dysfunctions observed in neuropsychiatric disorders. PMID:21515372

The genetics of normal and defective color vision.

PubMed

Neitz, Jay; Neitz, Maureen

2011-04-13

The contributions of genetics research to the science of normal and defective color vision over the previous few decades are reviewed emphasizing the developments in the 25years since the last anniversary issue of Vision Research. Understanding of the biology underlying color vision has been vaulted forward through the application of the tools of molecular genetics. For all their complexity, the biological processes responsible for color vision are more accessible than for many other neural systems. This is partly because of the wealth of genetic variations that affect color perception, both within and across species, and because components of the color vision system lend themselves to genetic manipulation. Mutations and rearrangements in the genes encoding the long, middle, and short wavelength sensitive cone pigments are responsible for color vision deficiencies and mutations have been identified that affect the number of cone types, the absorption spectra of the pigments, the functionality and viability of the cones, and the topography of the cone mosaic. The addition of an opsin gene, as occurred in the evolution of primate color vision, and has been done in experimental animals can produce expanded color vision capacities and this has provided insight into the underlying neural circuitry. Copyright © 2010 Elsevier Ltd. All rights reserved.

Brain connectivity study of joint attention using frequency-domain optical imaging technique

NASA Astrophysics Data System (ADS)

Chaudhary, Ujwal; Zhu, Banghe; Godavarty, Anuradha

2010-02-01

Autism is a socio-communication brain development disorder. It is marked by degeneration in the ability to respond to joint attention skill task, from as early as 12 to 18 months of age. This trait is used to distinguish autistic from nonautistic populations. In this study, diffuse optical imaging is being used to study brain connectivity for the first time in response to joint attention experience in normal adults. The prefrontal region of the brain was non-invasively imaged using a frequency-domain based optical imager. The imaging studies were performed on 11 normal right-handed adults and optical measurements were acquired in response to joint-attention based video clips. While the intensity-based optical data provides information about the hemodynamic response of the underlying neural process, the time-dependent phase-based optical data has the potential to explicate the directional information on the activation of the brain. Thus brain connectivity studies are performed by computing covariance/correlations between spatial units using this frequency-domain based optical measurements. The preliminary results indicate that the extent of synchrony and directional variation in the pattern of activation varies in the left and right frontal cortex. The results have significant implication for research in neural pathways associated with autism that can be mapped using diffuse optical imaging tools in the future.

Inspection of Space Station Cold Plate Using Visual and Automated Holographic Techniques

NASA Technical Reports Server (NTRS)

Decker, Arthur J.; Melis, Matthew E.; Weiland, Kenneth E.

1999-01-01

Real-time holography has been used to confirm the presence of non-uniformity in the construction of an International Space Station cold plate. Ultrasonic C-scans have previously shown suspected areas of cooling fin disbonds. But both neural-net processed and visual holography did not evidence any progressive permanent changes resulting from 3000 pressurization and relaxation cycles of a Dash 8 cold plate. Neural-net and visual inspections were performed of characteristic patterns generated from electronic time-average holograms of the vibrating cold plate. Normal modes of vibration were excited at very low amplitudes for this purpose, The neural nets were trained to flag very small changes in the mode shapes as encoded in the characteristic patterns. Both the whole cold plate and a zoomed region were inspected. The inspections were conducted before, after, and during pressurization and relaxation cycles of the cold plate. A water-filled cold plate was pressurized to 120 psig (827 kPa) and relaxed for each cycle. Each cycle required 5 seconds. Both the artificial neural networks and the inspectors were unable to detect changes in the mode shapes of the relaxed cold plate. The cold plate was also inspected visually using real-time holography and double-exposure holography. Regions of non-uniformity correlating with the C-scans were apparent, but the interference patterns did not change after 3000 pressurization and relaxation cycles. These tests constituted the first practical application of a neural-net inspection technique developed originally with support from the Director's Discretionary Fund at the Glenn Research Center at Lewis Field.

ANI-1: an extensible neural network potential with DFT accuracy at force field computational cost† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc05720a Click here for additional data file.

PubMed Central

Smith, J. S.

2017-01-01

Deep learning is revolutionizing many areas of science and technology, especially image, text, and speech recognition. In this paper, we demonstrate how a deep neural network (NN) trained on quantum mechanical (QM) DFT calculations can learn an accurate and transferable potential for organic molecules. We introduce ANAKIN-ME (Accurate NeurAl networK engINe for Molecular Energies) or ANI for short. ANI is a new method designed with the intent of developing transferable neural network potentials that utilize a highly-modified version of the Behler and Parrinello symmetry functions to build single-atom atomic environment vectors (AEV) as a molecular representation. AEVs provide the ability to train neural networks to data that spans both configurational and conformational space, a feat not previously accomplished on this scale. We utilized ANI to build a potential called ANI-1, which was trained on a subset of the GDB databases with up to 8 heavy atoms in order to predict total energies for organic molecules containing four atom types: H, C, N, and O. To obtain an accelerated but physically relevant sampling of molecular potential surfaces, we also proposed a Normal Mode Sampling (NMS) method for generating molecular conformations. Through a series of case studies, we show that ANI-1 is chemically accurate compared to reference DFT calculations on much larger molecular systems (up to 54 atoms) than those included in the training data set. PMID:28507695

Damage to the ventromedial prefrontal cortex reduces interpersonal disgust.

PubMed

Ciaramelli, Elisa; Sperotto, Rebecca G; Mattioli, Flavia; di Pellegrino, Giuseppe

2013-02-01

Disgust for contaminating objects (core disgust), immoral behaviors (moral disgust) and unsavory others (interpersonal disgust), have been assumed to be closely related. It is not clear, however, whether different forms of disgust are mediated by overlapping or specific neural substrates. We report that 10 patients with damage to the ventromedial prefrontal cortex (vmPFC) avoided behaviors that normally elicit interpersonal disgust (e.g. using the scarf of a busker) less frequently than healthy and brain-damaged controls, whereas they avoided core and moral disgust elicitors at normal rates. These results indicate that different forms of disgust are dissociated neurally. We propose that the vmPFC is causally (and selectively) involved in mediating interpersonal disgust, shaping patterns of social avoidance and approach.

Damage to the ventromedial prefrontal cortex reduces interpersonal disgust

PubMed Central

Ciaramelli, Elisa; Sperotto, Rebecca G.; Mattioli, Flavia

2013-01-01

Disgust for contaminating objects (core disgust), immoral behaviors (moral disgust) and unsavory others (interpersonal disgust), have been assumed to be closely related. It is not clear, however, whether different forms of disgust are mediated by overlapping or specific neural substrates. We report that 10 patients with damage to the ventromedial prefrontal cortex (vmPFC) avoided behaviors that normally elicit interpersonal disgust (e.g. using the scarf of a busker) less frequently than healthy and brain-damaged controls, whereas they avoided core and moral disgust elicitors at normal rates. These results indicate that different forms of disgust are dissociated neurally. We propose that the vmPFC is causally (and selectively) involved in mediating interpersonal disgust, shaping patterns of social avoidance and approach. PMID:22842816

Visual gravity cues in the interpretation of biological movements: neural correlates in humans.

PubMed

Maffei, Vincenzo; Indovina, Iole; Macaluso, Emiliano; Ivanenko, Yuri P; A Orban, Guy; Lacquaniti, Francesco

2015-01-01

Our visual system takes into account the effects of Earth gravity to interpret biological motion (BM), but the neural substrates of this process remain unclear. Here we measured functional magnetic resonance (fMRI) signals while participants viewed intact or scrambled stick-figure animations of walking, running, hopping, and skipping recorded at normal or reduced gravity. We found that regions sensitive to BM configuration in the occipito-temporal cortex (OTC) were more active for reduced than normal gravity but with intact stimuli only. Effective connectivity analysis suggests that predictive coding of gravity effects underlies BM interpretation. This process might be implemented by a family of snapshot neurons involved in action monitoring. Copyright © 2014 Elsevier Inc. All rights reserved.

Cognitive and Neural Correlates of Mathematical Giftedness in Adults and Children: A Review

PubMed Central

Myers, Timothy; Carey, Emma; Szűcs, Dénes

2017-01-01

Most mathematical cognition research has focused on understanding normal adult function and child development as well as mildly and moderately impaired mathematical skill, often labeled developmental dyscalculia and/or mathematical learning disability. In contrast, much less research is available on cognitive and neural correlates of gifted/excellent mathematical knowledge in adults and children. In order to facilitate further inquiry into this area, here we review 40 available studies, which examine the cognitive and neural basis of gifted mathematics. Studies associated a large number of cognitive factors with gifted mathematics, with spatial processing and working memory being the most frequently identified contributors. However, the current literature suffers from low statistical power, which most probably contributes to variability across findings. Other major shortcomings include failing to establish domain and stimulus specificity of findings, suggesting causation without sufficient evidence and the frequent use of invalid backward inference in neuro-imaging studies. Future studies must increase statistical power and neuro-imaging studies must rely on supporting behavioral data when interpreting findings. Studies should investigate the factors shown to correlate with math giftedness in a more specific manner and determine exactly how individual factors may contribute to gifted math ability. PMID:29118725

Attraction Basins as Gauges of Robustness against Boundary Conditions in Biological Complex Systems

PubMed Central

Demongeot, Jacques; Goles, Eric; Morvan, Michel; Noual, Mathilde; Sené, Sylvain

2010-01-01

One fundamental concept in the context of biological systems on which researches have flourished in the past decade is that of the apparent robustness of these systems, i.e., their ability to resist to perturbations or constraints induced by external or boundary elements such as electromagnetic fields acting on neural networks, micro-RNAs acting on genetic networks and even hormone flows acting both on neural and genetic networks. Recent studies have shown the importance of addressing the question of the environmental robustness of biological networks such as neural and genetic networks. In some cases, external regulatory elements can be given a relevant formal representation by assimilating them to or modeling them by boundary conditions. This article presents a generic mathematical approach to understand the influence of boundary elements on the dynamics of regulation networks, considering their attraction basins as gauges of their robustness. The application of this method on a real genetic regulation network will point out a mathematical explanation of a biological phenomenon which has only been observed experimentally until now, namely the necessity of the presence of gibberellin for the flower of the plant Arabidopsis thaliana to develop normally. PMID:20700525

Reorganization of pathological control functions of memory-A neural model for tissue healing by shock waves

NASA Astrophysics Data System (ADS)

Wess, Othmar

2005-04-01

Since 1980 shock waves have proven effective in the field of extracorporeal lithotripsy. More than 10 years ago shock waves were successfully applied for various indications such as chronic pain, non-unions and, recently, for angina pectoris. These fields do not profit from the disintegration power but from stimulating and healing effects of shock waves. Increased metabolism and neo-vascularization are reported after shock wave application. According to C. J. Wang, a biological cascade is initiated, starting with a stimulating effect of physical energy resulting in increased circulation and metabolism. Pathological memory of neural control patterns is considered the reason for different pathologies characterized by insufficient metabolism. This paper presents a neural model for reorganization of pathological reflex patterns. The model acts on associative memory functions of the brain based on modification of synaptic junctions. Accordingly, pathological memory effects of the autonomous nervous system are reorganized by repeated application of shock waves followed by development of normal reflex patterns. Physiologic control of muscle and vascular tone is followed by increased metabolism and tissue repair. The memory model may explain hyper-stimulation effects in pain therapy.

Neural Network Based Intrusion Detection System for Critical Infrastructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Todd Vollmer; Ondrej Linda; Milos Manic

2009-07-01

Resiliency and security in control systems such as SCADA and Nuclear plant’s in today’s world of hackers and malware are a relevant concern. Computer systems used within critical infrastructures to control physical functions are not immune to the threat of cyber attacks and may be potentially vulnerable. Tailoring an intrusion detection system to the specifics of critical infrastructures can significantly improve the security of such systems. The IDS-NNM – Intrusion Detection System using Neural Network based Modeling, is presented in this paper. The main contributions of this work are: 1) the use and analyses of real network data (data recordedmore » from an existing critical infrastructure); 2) the development of a specific window based feature extraction technique; 3) the construction of training dataset using randomly generated intrusion vectors; 4) the use of a combination of two neural network learning algorithms – the Error-Back Propagation and Levenberg-Marquardt, for normal behavior modeling. The presented algorithm was evaluated on previously unseen network data. The IDS-NNM algorithm proved to be capable of capturing all intrusion attempts presented in the network communication while not generating any false alerts.« less

A fast button surface defects detection method based on convolutional neural network

NASA Astrophysics Data System (ADS)

Liu, Lizhe; Cao, Danhua; Wu, Songlin; Wu, Yubin; Wei, Taoran

2018-01-01

Considering the complexity of the button surface texture and the variety of buttons and defects, we propose a fast visual method for button surface defect detection, based on convolutional neural network (CNN). CNN has the ability to extract the essential features by training, avoiding designing complex feature operators adapted to different kinds of buttons, textures and defects. Firstly, we obtain the normalized button region and then use HOG-SVM method to identify the front and back side of the button. Finally, a convolutional neural network is developed to recognize the defects. Aiming at detecting the subtle defects, we propose a network structure with multiple feature channels input. To deal with the defects of different scales, we take a strategy of multi-scale image block detection. The experimental results show that our method is valid for a variety of buttons and able to recognize all kinds of defects that have occurred, including dent, crack, stain, hole, wrong paint and uneven. The detection rate exceeds 96%, which is much better than traditional methods based on SVM and methods based on template match. Our method can reach the speed of 5 fps on DSP based smart camera with 600 MHz frequency.

Restoring visual perception using microsystem technologies: engineering and manufacturing perspectives.

PubMed

Krisch, I; Hosticka, B J

2007-01-01

Microsystem technologies offer significant advantages in the development of neural prostheses. In the last two decades, it has become feasible to develop intelligent prostheses that are fully implantable into the human body with respect to functionality, complexity, size, weight, and compactness. Design and development enforce collaboration of various disciplines including physicians, engineers, and scientists. The retina implant system can be taken as one sophisticated example of a prosthesis which bypasses neural defects and enables direct electrical stimulation of nerve cells. This micro implantable visual prosthesis assists blind patients to return to the normal course of life. The retina implant is intended for patients suffering from retinitis pigmentosa or macular degeneration. In this contribution, we focus on the epiretinal prosthesis and discuss topics like system design, data and power transfer, fabrication, packaging and testing. In detail, the system is based upon an implantable micro electro stimulator which is powered and controlled via a wireless inductive link. Microelectronic circuits for data encoding and stimulation are assembled on flexible substrates with an integrated electrode array. The implant system is encapsulated using parylene C and silicone rubber. Results extracted from experiments in vivo demonstrate the retinotopic activation of the visual cortex.

What choline metabolism can tell us about the underlying mechanisms of fetal alcohol spectrum disorders.

PubMed

Zeisel, Steven H

2011-10-01

The consequences of fetal exposure to alcohol are very diverse and the likely molecular mechanisms involved must be able to explain how so many developmental processes could go awry. If pregnant rat dams are fed alcohol, their pups develop abnormalities characteristic of fetal alcohol spectrum disorders (FASD), but if these rat dams were also treated with choline, the effects from ethanol were attenuated in their pups. Choline is an essential nutrient in humans, and is an important methyl group donor. Alcohol exposure disturbs the metabolism of choline and other methyl donors. Availability of choline during gestation directly influences epigenetic marks on DNA and histones, and alters gene expression needed for normal neural and endothelial progenitor cell proliferation. Maternal diets low in choline alter development of the mouse hippocampus, and decrement memory for life. Women eating low-choline diets have an increased risk of having an infant with a neural tube or orofacial cleft birth defect. Thus, the varied effects of choline could affect the expression of FASD, and studies on choline might shed some light on the underlying molecular mechanisms responsible for FASD.

Fine-tuned SRF activity controls asymmetrical neuronal outgrowth: implications for cortical migration, neural tissue lamination and circuit assembly

PubMed Central

Scandaglia, Marilyn; Benito, Eva; Morenilla-Palao, Cruz; Fiorenza, Anna; del Blanco, Beatriz; Coca, Yaiza; Herrera, Eloísa; Barco, Angel

2015-01-01

The stimulus-regulated transcription factor Serum Response Factor (SRF) plays an important role in diverse neurodevelopmental processes related to structural plasticity and motile functions, although its precise mechanism of action has not yet been established. To further define the role of SRF in neural development and distinguish between cell-autonomous and non cell-autonomous effects, we bidirectionally manipulated SRF activity through gene transduction assays that allow the visualization of individual neurons and their comparison with neighboring control cells. In vitro assays showed that SRF promotes survival and filopodia formation and is required for normal asymmetric neurite outgrowth, indicating that its activation favors dendrite enlargement versus branching. In turn, in vivo experiments demonstrated that SRF-dependent regulation of neuronal morphology has important consequences in the developing cortex and retina, affecting neuronal migration, dendritic and axonal arborization and cell positioning in these laminated tissues. Overall, our results show that the controlled and timely activation of SRF is essential for the coordinated growth of neuronal processes, suggesting that this event regulates the switch between neuronal growth and branching during developmental processes. PMID:26638868

A Range-Normalization Model of Context-Dependent Choice: A New Model and Evidence

PubMed Central

Camerer, Colin

2012-01-01

Most utility theories of choice assume that the introduction of an irrelevant option (called the decoy) to a choice set does not change the preference between existing options. On the contrary, a wealth of behavioral data demonstrates the dependence of preference on the decoy and on the context in which the options are presented. Nevertheless, neural mechanisms underlying context-dependent preference are poorly understood. In order to shed light on these mechanisms, we design and perform a novel experiment to measure within-subject decoy effects. We find within-subject decoy effects similar to what have been shown previously with between-subject designs. More importantly, we find that not only are the decoy effects correlated, pointing to similar underlying mechanisms, but also these effects increase with the distance of the decoy from the original options. To explain these observations, we construct a plausible neuronal model that can account for decoy effects based on the trial-by-trial adjustment of neural representations to the set of available options. This adjustment mechanism, which we call range normalization, occurs when the nervous system is required to represent different stimuli distinguishably, while being limited to using bounded neural activity. The proposed model captures our experimental observations and makes new predictions about the influence of the choice set size on the decoy effects, which are in contrast to previous models of context-dependent choice preference. Critically, unlike previous psychological models, the computational resource required by our range-normalization model does not increase exponentially as the set size increases. Our results show that context-dependent choice behavior, which is commonly perceived as an irrational response to the presence of irrelevant options, could be a natural consequence of the biophysical limits of neural representation in the brain. PMID:22829761

Neural plasticity expressed in central auditory structures with and without tinnitus

PubMed Central

Roberts, Larry E.; Bosnyak, Daniel J.; Thompson, David C.

2012-01-01

Sensory training therapies for tinnitus are based on the assumption that, notwithstanding neural changes related to tinnitus, auditory training can alter the response properties of neurons in auditory pathways. To assess this assumption, we investigated whether brain changes induced by sensory training in tinnitus sufferers and measured by electroencephalography (EEG) are similar to those induced in age and hearing loss matched individuals without tinnitus trained on the same auditory task. Auditory training was given using a 5 kHz 40-Hz amplitude-modulated (AM) sound that was in the tinnitus frequency region of the tinnitus subjects and enabled extraction of the 40-Hz auditory steady-state response (ASSR) and P2 transient response known to localize to primary and non-primary auditory cortex, respectively. P2 amplitude increased over training sessions equally in participants with tinnitus and in control subjects, suggesting normal remodeling of non-primary auditory regions in tinnitus. However, training-induced changes in the ASSR differed between the tinnitus and control groups. In controls the phase delay between the 40-Hz response and stimulus waveforms reduced by about 10° over training, in agreement with previous results obtained in young normal hearing individuals. However, ASSR phase did not change significantly with training in the tinnitus group, although some participants showed phase shifts resembling controls. On the other hand, ASSR amplitude increased with training in the tinnitus group, whereas in controls this response (which is difficult to remodel in young normal hearing subjects) did not change with training. These results suggest that neural changes related to tinnitus altered how neural plasticity was expressed in the region of primary but not non-primary auditory cortex. Auditory training did not reduce tinnitus loudness although a small effect on the tinnitus spectrum was detected. PMID:22654738

In vitro 3D regeneration-like growth of human patient brain tissue.

PubMed

Tang-Schomer, M D; Wu, W B; Kaplan, D L; Bookland, M J

2018-05-01

In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 μm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models. Copyright © 2018 John Wiley & Sons, Ltd.

An infectious disease/fever screening radar system which stratifies higher-risk patients within ten seconds using a neural network and the fuzzy grouping method.

PubMed

Sun, Guanghao; Matsui, Takemi; Hakozaki, Yukiya; Abe, Shigeto

2015-03-01

To classify higher-risk influenza patients within 10 s, we developed an infectious disease and fever screening radar system. The system screens infected patients based on vital signs, i.e., respiration rate measured by a radar, heart rate by a finger-tip photo-reflector, and facial temperature by a thermography. The system segregates subjects into higher-risk influenza (HR-I) group, lower-risk influenza (LR-I) group, and non-influenza (Non-I) group using a neural network and fuzzy clustering method (FCM). We conducted influenza screening for 35 seasonal influenza patients and 48 normal control subjects at the Japan Self-Defense Force Central Hospital. Pulse oximetry oxygen saturation (SpO2) was measured as a reference. The system classified 17 subjects into HR-I group, 26 into LR-I group, and 40 into Non-I group. Ten out of the 17 HR-I subjects indicated SpO2 <96%, whereas only two out of the 26 LR-I subjects showed SpO2 <96%. The chi-squared test revealed a significant difference in the ratio of subjects showed SpO2 <96% between HR-I and LR-I group (p < 0.001). There were zero and nine normal control subjects in HR-I and LR-I groups, respectively, and there was one influenza patient in Non-I group. The combination of neural network and FCM achieved efficient detection of higher-risk influenza patients who indicated SpO2 96% within 10 s. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Encoding of sound envelope transients in the auditory cortex of juvenile rats and adult rats.

PubMed

Lu, Qi; Jiang, Cuiping; Zhang, Jiping

2016-02-01

Accurate neural processing of time-varying sound amplitude and spectral information is vital for species-specific communication. During postnatal development, cortical processing of sound frequency undergoes progressive refinement; however, it is not clear whether cortical processing of sound envelope transients also undergoes age-related changes. We determined the dependence of neural response strength and first-spike latency on sound rise-fall time across sound levels in the primary auditory cortex (A1) of juvenile (P20-P30) rats and adult (8-10 weeks) rats. A1 neurons were categorized as "all-pass", "short-pass", or "mixed" ("all-pass" at high sound levels to "short-pass" at lower sound levels) based on the normalized response strength vs. rise-fall time functions across sound levels. The proportions of A1 neurons within each of the three categories in juvenile rats were similar to that in adult rats. In general, with increasing rise-fall time, the average response strength decreased and the average first-spike latency increased in A1 neurons of both groups. At a given sound level and rise-fall time, the average normalized neural response strength did not differ significantly between the two age groups. However, the A1 neurons in juvenile rats showed greater absolute response strength, longer first-spike latency compared to those in adult rats. In addition, at a constant sound level, the average first-spike latency of juvenile A1 neurons was more sensitive to changes in rise-fall time. Our results demonstrate the dependence of the responses of rat A1 neurons on sound rise-fall time, and suggest that the response latency exhibit some age-related changes in cortical representation of sound envelope rise time. Copyright © 2015 Elsevier Ltd. All rights reserved.

Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart.

PubMed

Poelmann, Robert E; Gittenberger-de Groot, Adriana C; Biermans, Marcel W M; Dolfing, Anne I; Jagessar, Armand; van Hattum, Sam; Hoogenboom, Amanda; Wisse, Lambertus J; Vicente-Steijn, Rebecca; de Bakker, Merijn A G; Vonk, Freek J; Hirasawa, Tatsuya; Kuratani, Shigeru; Richardson, Michael K

2017-01-01

Cardiac outflow tract patterning and cell contribution are studied using an evo-devo approach to reveal insight into the development of aorto-pulmonary septation. We studied embryonic stages of reptile hearts (lizard, turtle and crocodile) and compared these to avian and mammalian development. Immunohistochemistry allowed us to indicate where the essential cell components in the outflow tract and aortic sac were deployed, more specifically endocardial, neural crest and second heart field cells. The neural crest-derived aorto-pulmonary septum separates the pulmonary trunk from both aortae in reptiles, presenting with a left visceral and a right systemic aorta arising from the unseptated ventricle. Second heart field-derived cells function as flow dividers between both aortae and between the two pulmonary arteries. In birds, the left visceral aorta disappears early in development, while the right systemic aorta persists. This leads to a fusion of the aorto-pulmonary septum and the aortic flow divider (second heart field population) forming an avian aorto-pulmonary septal complex. In mammals, there is also a second heart field-derived aortic flow divider, albeit at a more distal site, while the aorto-pulmonary septum separates the aortic trunk from the pulmonary trunk. As in birds there is fusion with second heart field-derived cells albeit from the pulmonary flow divider as the right 6th pharyngeal arch artery disappears, resulting in a mammalian aorto-pulmonary septal complex. In crocodiles, birds and mammals, the main septal and parietal endocardial cushions receive neural crest cells that are functional in fusion and myocardialization of the outflow tract septum. Longer-lasting septation in crocodiles demonstrates a heterochrony in development. In other reptiles with no indication of incursion of neural crest cells, there is either no myocardialized outflow tract septum (lizard) or it is vestigial (turtle). Crocodiles are unique in bearing a central shunt, the foramen of Panizza, between the roots of both aortae. Finally, the soft-shell turtle investigated here exhibits a spongy histology of the developing carotid arteries supposedly related to regulation of blood flow during pharyngeal excretion in this species. This is the first time that is shown that an interplay of second heart field-derived flow dividers with a neural crest-derived cell population is a variable but common, denominator across all species studied for vascular patterning and outflow tract septation. The observed differences in normal development of reptiles may have impact on the understanding of development of human congenital outflow tract malformations.

Enhanced pure-tone pitch discrimination among persons with autism but not Asperger syndrome.

PubMed

Bonnel, Anna; McAdams, Stephen; Smith, Bennett; Berthiaume, Claude; Bertone, Armando; Ciocca, Valter; Burack, Jacob A; Mottron, Laurent

2010-07-01

Persons with Autism spectrum disorders (ASD) display atypical perceptual processing in visual and auditory tasks. In vision, Bertone, Mottron, Jelenic, and Faubert (2005) found that enhanced and diminished visual processing is linked to the level of neural complexity required to process stimuli, as proposed in the neural complexity hypothesis. Based on these findings, Samson, Mottron, Jemel, Belin, and Ciocca (2006) proposed to extend the neural complexity hypothesis to the auditory modality. They hypothesized that persons with ASD should display enhanced performance for simple tones that are processed in primary auditory cortical regions, but diminished performance for complex tones that require additional processing in associative auditory regions, in comparison to typically developing individuals. To assess this hypothesis, we designed four auditory discrimination experiments targeting pitch, non-vocal and vocal timbre, and loudness. Stimuli consisted of spectro-temporally simple and complex tones. The participants were adolescents and young adults with autism, Asperger syndrome, and typical developmental histories, all with IQs in the normal range. Consistent with the neural complexity hypothesis and enhanced perceptual functioning model of ASD (Mottron, Dawson, Soulières, Hubert, & Burack, 2006), the participants with autism, but not with Asperger syndrome, displayed enhanced pitch discrimination for simple tones. However, no discrimination-thresholds differences were found between the participants with ASD and the typically developing persons across spectrally and temporally complex conditions. These findings indicate that enhanced pure-tone pitch discrimination may be a cognitive correlate of speech-delay among persons with ASD. However, auditory discrimination among this group does not appear to be directly contingent on the spectro-temporal complexity of the stimuli. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Neural autoantibodies and neurophysiologic abnormalities in patients exposed to molds in water-damaged buildings.

PubMed

Campbell, Andrew W; Thrasher, Jack D; Madison, Roberta A; Vojdani, Aristo; Gray, Michael R; Johnson, Al

2003-08-01

Adverse health effects of fungal bioaerosols on occupants of water-damaged homes and other buildings have been reported. Recently, it has been suggested that mold exposure causes neurological injury. The authors investigated neurological antibodies and neurophysiological abnormalities in patients exposed to molds at home who developed symptoms of peripheral neuropathy (i.e., numbness, tingling, tremors, and muscle weakness in the extremities). Serum samples were collected and analyzed with the enzyme-linked immunosorbent assay (ELISA) technique for antibodies to myelin basic protein, myelin-associated glycoprotein, ganglioside GM1, sulfatide, myelin oligodendrocyte glycoprotein, alpha-B-crystallin, chondroitin sulfate, tubulin, and neurofilament. Antibodies to molds and mycotoxins were also determined with ELISA, as reported previously. Neurophysiologic evaluations for latency, amplitude, and velocity were performed on 4 motor nerves (median, ulnar, peroneal, and tibial), and for latency and amplitude on 3 sensory nerves (median, ulnar, and sural). Patients with documented, measured exposure to molds had elevated titers of antibodies (immunoglobulin [Ig]A, IgM, and IgG) to neural-specific antigens. Nerve conduction studies revealed 4 patient groupings: (1) mixed sensory-motor polyneuropathy (n = 55, abnormal), (2) motor neuropathy (n = 17, abnormal), (3) sensory neuropathy (n = 27, abnormal), and (4) those with symptoms but no neurophysiological abnormalities (n = 20, normal controls). All groups showed significantly increased autoantibody titers for all isotypes (IgA, IgM, and IgG) of antibodies to neural antigens when compared with 500 healthy controls. Groups 1 through 3 also exhibited abnormal neurophysiologic findings. The authors concluded that exposure to molds in water-damaged buildings increased the risk for development of neural autoantibodies, peripheral neuropathy, and neurophysiologic abnormalities in exposed individuals.

A galvanotaxis assay for analysis of neural precursor cell migration kinetics in an externally applied direct current electric field.

PubMed

Babona-Pilipos, Robart; Popovic, Milos R; Morshead, Cindi M

2012-10-13

The discovery of neural stem and progenitor cells (collectively termed neural precursor cells) (NPCs) in the adult mammalian brain has led to a body of research aimed at utilizing the multipotent and proliferative properties of these cells for the development of neuroregenerative strategies. A critical step for the success of such strategies is the mobilization of NPCs toward a lesion site following exogenous transplantation or to enhance the response of the endogenous precursors that are found in the periventricular region of the CNS. Accordingly, it is essential to understand the mechanisms that promote, guide, and enhance NPC migration. Our work focuses on the utilization of direct current electric fields (dcEFs) to promote and direct NPC migration - a phenomenon known as galvanotaxis. Endogenous physiological electric fields function as critical cues for cell migration during normal development and wound repair. Pharmacological disruption of the trans-neural tube potential in axolotl embryos causes severe developmental malformations(1). In the context of wound healing, the rate of repair of wounded cornea is directly correlated with the magnitude of the epithelial wound potential that arises after injury, as shown by pharmacological enhancement or disruption of this dcEF(2-3). We have demonstrated that adult subependymal NPCs undergo rapid and directed cathodal migration in vitro when exposed to an externally applied dcEF. In this protocol we describe our lab's techniques for creating a simple and effective galvanotaxis assay for high-resolution, long-term observation of directed cell body translocation (migration) on a single-cell level. This assay would be suitable for investigating the mechanisms that regulate dcEF transduction into cellular motility through the use of transgenic or knockout mice, short interfering RNA, or specific receptor agonists/antagonists.

Wireless, High-Bandwidth Recordings from Non-Human Primate Motor Cortex using a Scalable 16-Ch Implantable Microsystem

PubMed Central

Borton, David A.; Song, Yoon-Kyu; Patterson, William R.; Bull, Christopher W.; Park, Sunmee; Laiwalla, Farah; Donoghue, John P.; Nurmikko, Arto V.

2013-01-01

A multitude of neuroengineering challenges exist today in creating practical, chronic multichannel neural recording systems for primate research and human clinical application. Specifically, a) the persistent wired connections limit patient mobility from the recording system, b) the transfer of high bandwidth signals to external (even distant) electronics normally forces premature data reduction, and c) the chronic susceptibility to infection due to the percutaneous nature of the implants all severely hinder the success of neural prosthetic systems. Here we detail one approach to overcome these limitations: an entirely implantable, wirelessly communicating, integrated neural recording microsystem, dubbed the Brain Implantable Chip (BIC). PMID:19964128

Top-down modulation: the crossroads of perception, attention and memory

NASA Astrophysics Data System (ADS)

Gazzaley, Adam

2010-02-01

Research in our laboratory focuses on understanding the neural mechanisms that serve at the crossroads of perception, memory and attention, specifically exploring how brain region interactions underlie these abilities. To accomplish this, we study top-down modulation, the process by which we enhance neural activity associated with relevant information and suppress activity for irrelevant information, thus establishing a neural basis for all higher-order cognitive operations. We also study alterations in top-down modulation that occur with normal aging. Our experiments are performed on human participants, using a multimodal approach that integrates functional MRI (fMRI), transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

Kif11 dependent cell cycle progression in radial glial cells is required for proper neurogenesis in the zebrafish neural tube.

PubMed

Johnson, Kimberly; Moriarty, Chelsea; Tania, Nessy; Ortman, Alissa; DiPietrantonio, Kristina; Edens, Brittany; Eisenman, Jean; Ok, Deborah; Krikorian, Sarah; Barragan, Jessica; Golé, Christophe; Barresi, Michael J F

2014-03-01

Radial glia serve as the resident neural stem cells in the embryonic vertebrate nervous system, and their proliferation must be tightly regulated to generate the correct number of neuronal and glial cell progeny in the neural tube. During a forward genetic screen, we recently identified a zebrafish mutant in the kif11 loci that displayed a significant increase in radial glial cell bodies at the ventricular zone of the spinal cord. Kif11, also known as Eg5, is a kinesin-related, plus-end directed motor protein responsible for stabilizing and separating the bipolar mitotic spindle. We show here that Gfap+ radial glial cells express kif11 in the ventricular zone and floor plate. Loss of Kif11 by mutation or pharmacological inhibition with S-trityl-L-cysteine (STLC) results in monoastral spindle formation in radial glial cells, which is characteristic of mitotic arrest. We show that M-phase radial glia accumulate over time at the ventricular zone in kif11 mutants and STLC treated embryos. Mathematical modeling of the radial glial accumulation in kif11 mutants not only confirmed an ~226× delay in mitotic exit (likely a mitotic arrest), but also predicted two modes of increased cell death. These modeling predictions were supported by an increase in the apoptosis marker, anti-activated Caspase-3, which was also found to be inversely proportional to a decrease in cell proliferation. In addition, treatment with STLC at different stages of neural development uncovered two critical periods that most significantly require Kif11 function for stem cell progression through mitosis. We also show that loss of Kif11 function causes specific reductions in oligodendroglia and secondary interneurons and motorneurons, suggesting these later born populations require proper radial glia division. Despite these alterations to cell cycle dynamics, survival, and neurogenesis, we document unchanged cell densities within the neural tube in kif11 mutants, suggesting that a mechanism of compensatory regulation may exist to maintain overall proportions in the neural tube. We propose a model in which Kif11 normally functions during mitotic spindle formation to facilitate the progression of radial glia through mitosis, which leads to the maturation of progeny into specific secondary neuronal and glial lineages in the developing neural tube. Copyright © 2014. Published by Elsevier Inc.

Kif11 dependent cell cycle progression in radial glial cells is required for proper neurogenesis in the zebrafish neural tube

PubMed Central

Johnson, Kimberly; Moriarty, Chelsea; Tania, Nessy; Ortman, Alissa; DiPietrantonio, Kristina; Edens, Brittany; Eisenman, Jean; Ok, Deborah; Krikorian, Sarah; Barragan, Jessica; Gole, Christophe; Barresi, Michael J.F.

2014-01-01

Radial glia serve as the resident neural stem cells in the embryonic vertebrate nervous system, and their proliferation must be tightly regulated to generate the correct number of neuronal and glial cell progeny in the neural tube. During a forward genetic screen, we recently identified a zebrafish mutant in the kif11 loci that displayed a significant increase in radial glial cell bodies at the ventricular zone of the spinal cord. Kif11, also known as Eg5, is a kinesin-related, plus-end directed motor protein responsible for stabilizing and separating the bipolar mitotic spindle. We show here that Gfap+ radial glial cells express kif11 in the ventricular zone and floor plate. Loss of Kif11 by mutation or pharmacological inhibition with S-trityl-L-cysteine (STLC) results in monoastral spindle formation in radial glial cells, which is characteristic of mitotic arrest. We show that M-phase radial glia accumulate over time at the ventricular zone in kif11 mutants and STLC treated embryos. Mathematical modeling of the radial glial accumulation in kif11 mutants not only confirmed an ~226x delay in mitotic exit (likely a mitotic arrest), but also predicted two modes of increased cell death. These modeling predictions were supported by an increase in the apoptosis marker, anti-activated Caspase-3, which was also found to be inversely proportional to a decrease in cell proliferation. In addition, treatment with STLC at different stages of neural development uncovered two critical periods that most significantly require Kif11 function for stem cell progression through mitosis. We also show that loss of Kif11 function causes specific reductions in oligodendroglia and secondary interneurons and motorneurons, suggesting these later born populations require proper radial glia division. Despite these alterations to cell cycle dynamics, survival, and neurogenesis, we document unchanged cell densities within the neural tube in kif11 mutants, suggesting that a mechanism of compensatory regulation may exist to maintain overall proportions in the neural tube. We propose a model in which Kif11 normally functions during mitotic spindle formation to facilitate the progression of radial glia through mitosis, which leads to the maturation of progeny into specific secondary neuronal and glial lineages in the developing neural tube. PMID:24370453

Digital transcriptome profiling of normal and glioblastoma-derived neural stem cells identifies genes associated with patient survival

PubMed Central

2012-01-01

Background Glioblastoma multiforme, the most common type of primary brain tumor in adults, is driven by cells with neural stem (NS) cell characteristics. Using derivation methods developed for NS cells, it is possible to expand tumorigenic stem cells continuously in vitro. Although these glioblastoma-derived neural stem (GNS) cells are highly similar to normal NS cells, they harbor mutations typical of gliomas and initiate authentic tumors following orthotopic xenotransplantation. Here, we analyzed GNS and NS cell transcriptomes to identify gene expression alterations underlying the disease phenotype. Methods Sensitive measurements of gene expression were obtained by high-throughput sequencing of transcript tags (Tag-seq) on adherent GNS cell lines from three glioblastoma cases and two normal NS cell lines. Validation by quantitative real-time PCR was performed on 82 differentially expressed genes across a panel of 16 GNS and 6 NS cell lines. The molecular basis and prognostic relevance of expression differences were investigated by genetic characterization of GNS cells and comparison with public data for 867 glioma biopsies. Results Transcriptome analysis revealed major differences correlated with glioma histological grade, and identified misregulated genes of known significance in glioblastoma as well as novel candidates, including genes associated with other malignancies or glioma-related pathways. This analysis further detected several long non-coding RNAs with expression profiles similar to neighboring genes implicated in cancer. Quantitative PCR validation showed excellent agreement with Tag-seq data (median Pearson r = 0.91) and discerned a gene set robustly distinguishing GNS from NS cells across the 22 lines. These expression alterations include oncogene and tumor suppressor changes not detected by microarray profiling of tumor tissue samples, and facilitated the identification of a GNS expression signature strongly associated with patient survival (P = 1e-6, Cox model). Conclusions These results support the utility of GNS cell cultures as a model system for studying the molecular processes driving glioblastoma and the use of NS cells as reference controls. The association between a GNS expression signature and survival is consistent with the hypothesis that a cancer stem cell component drives tumor growth. We anticipate that analysis of normal and malignant stem cells will be an important complement to large-scale profiling of primary tumors. PMID:23046790

Model for neural signaling leap statistics

NASA Astrophysics Data System (ADS)

Chevrollier, Martine; Oriá, Marcos

2011-03-01

We present a simple model for neural signaling leaps in the brain considering only the thermodynamic (Nernst) potential in neuron cells and brain temperature. We numerically simulated connections between arbitrarily localized neurons and analyzed the frequency distribution of the distances reached. We observed qualitative change between Normal statistics (with T = 37.5°C, awaken regime) and Lévy statistics (T = 35.5°C, sleeping period), characterized by rare events of long range connections.

Advanced Reactors-Intermediate Heat Exchanger (IHX) Coupling: Theoretical Modeling and Experimental Validation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Utgikar, Vivek; Sun, Xiaodong; Christensen, Richard

2016-12-29

The overall goal of the research project was to model the behavior of the advanced reactorintermediate heat exchange system and to develop advanced control techniques for off-normal conditions. The specific objectives defined for the project were: 1. To develop the steady-state thermal hydraulic design of the intermediate heat exchanger (IHX); 2. To develop mathematical models to describe the advanced nuclear reactor-IHX-chemical process/power generation coupling during normal and off-normal operations, and to simulate models using multiphysics software; 3. To develop control strategies using genetic algorithm or neural network techniques and couple these techniques with the multiphysics software; 4. To validate themore » models experimentally The project objectives were accomplished by defining and executing four different tasks corresponding to these specific objectives. The first task involved selection of IHX candidates and developing steady state designs for those. The second task involved modeling of the transient and offnormal operation of the reactor-IHX system. The subsequent task dealt with the development of control strategies and involved algorithm development and simulation. The last task involved experimental validation of the thermal hydraulic performances of the two prototype heat exchangers designed and fabricated for the project at steady state and transient conditions to simulate the coupling of the reactor- IHX-process plant system. The experimental work utilized the two test facilities at The Ohio State University (OSU) including one existing High-Temperature Helium Test Facility (HTHF) and the newly developed high-temperature molten salt facility.« less

History, heresy and radiology in scientific discovery.

PubMed

McCredie, J

2009-10-01

Nowadays, most drugs reach the market after research has established their pharmacology, safety and efficacy. That was not always the case 50 years ago. Thalidomide was used before its target cell or mode of action were known. Commencing with the thalidomide catastrophe--an epidemic of gross birth defects (1958-1962)--thalidomide's origins are revisited to show how this drug came to be made and sold in the 1950s. Thalidomide intersected with Australian radiology in the 1970s. The site and mode of action of the drug was deduced from X-rays of thalidomide-induced bone defects, which have classical radiological signs of sensory neuropathic osteoarthropathy. The longitudinal reduction deformities follow the distribution of segmental sensory innervation of the limb skeleton, indicating neural crest as the target organ. Injury to one level of neural crest halts normal neurotrophism and deletes the dependent segment--a previously unrecognised embryonic mechanism that explains most non-genetic birth defects. The final common pathway is neural crest injury and failure of normal neurotrophism to result in longitudinal reduction deformities, for example, phocomelia.

About turn: how object orientation affects categorisation and mental rotation.

PubMed

Milivojevic, Branka; Hamm, Jeff P; Corballis, Michael C

2011-11-01

High-density ERPs evoked by rotated alphanumeric characters were examined to determine how neural processing is affected by stimulus orientation during letter/digit classifications and during mirror/normal discriminations. The former task typically produces response times that are unaffected by stimulus orientation while the latter is thought to require mental rotation. Sensitivity to orientation was first observed around 100-140 ms and this effect was attributed to differences in low-level features between vertical and oblique orientations. Subsequently, character misorientation amplified the N170, a neural marker of object classification, between 160 and 220 ms. Top-down processing is reflected in the ERPs beginning at 280-320 ms and this time range may reflect binding of ventral and dorsal stream information. In the case of mirror-normal discrimination these top-down processes can lead to mental rotation between 340 and 700 ms. Therefore, although neural processing reflects object orientation, these effects do not translate into increases in reaction-times or impaired accuracy for categorisation, and precede those that do in the mental-rotation task. Copyright © 2011 Elsevier Ltd. All rights reserved.

Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila.

PubMed

Chihara, Takahiro; Kitabayashi, Aki; Morimoto, Michie; Takeuchi, Ken-ichi; Masuyama, Kaoru; Tonoki, Ayako; Davis, Ronald L; Wang, Jing W; Miura, Masayuki

2014-06-01

Sensory and cognitive performance decline with age. Neural dysfunction caused by nerve death in senile dementia and neurodegenerative disease has been intensively studied; however, functional changes in neural circuits during the normal aging process are not well understood. Caspases are key regulators of cell death, a hallmark of age-related neurodegeneration. Using a genetic probe for caspase-3-like activity (DEVDase activity), we have mapped age-dependent neuronal changes in the adult brain throughout the lifespan of Drosophila. Spatio-temporally restricted caspase activation was observed in the antennal lobe and ellipsoid body, brain structures required for olfaction and visual place memory, respectively. We also found that caspase was activated in an age-dependent manner in specific subsets of Drosophila olfactory receptor neurons (ORNs), Or42b and Or92a neurons. These neurons are essential for mediating innate attraction to food-related odors. Furthermore, age-induced impairments of neural transmission and attraction behavior could be reversed by specific inhibition of caspase in these ORNs, indicating that caspase activation in Or42b and Or92a neurons is responsible for altering animal behavior during normal aging.

Normalized value coding explains dynamic adaptation in the human valuation process.

PubMed

Khaw, Mel W; Glimcher, Paul W; Louie, Kenway

2017-11-28

The notion of subjective value is central to choice theories in ecology, economics, and psychology, serving as an integrated decision variable by which options are compared. Subjective value is often assumed to be an absolute quantity, determined in a static manner by the properties of an individual option. Recent neurobiological studies, however, have shown that neural value coding dynamically adapts to the statistics of the recent reward environment, introducing an intrinsic temporal context dependence into the neural representation of value. Whether valuation exhibits this kind of dynamic adaptation at the behavioral level is unknown. Here, we show that the valuation process in human subjects adapts to the history of previous values, with current valuations varying inversely with the average value of recently observed items. The dynamics of this adaptive valuation are captured by divisive normalization, linking these temporal context effects to spatial context effects in decision making as well as spatial and temporal context effects in perception. These findings suggest that adaptation is a universal feature of neural information processing and offer a unifying explanation for contextual phenomena in fields ranging from visual psychophysics to economic choice.

Neural cells derived from adult bone marrow and umbilical cord blood.

PubMed

Sanchez-Ramos, Juan R

2002-09-15

Under experimental conditions, tissue-specific stem cells have been shown to give rise to cell lineages not normally found in the organ or tissue of residence. Neural stem cells from fetal brain have been shown to give rise to blood cell lines and conversely, bone marrow stromal cells have been reported to generate skeletal and cardiac muscle, oval hepatocytes, as well as glia and neuron-like cells. This article reviews studies in which cells from postnatal bone marrow or umbilical cord blood were induced to proliferate and differentiate into glia and neurons, cellular lineages that are not their normal destiny. The review encompasses in vitro and in vivo studies with focus on experimental variables, such as the source and characterization of cells, cell-tracking methods, and markers of neural differentiation. The existence of stem/progenitor cells with previously unappreciated proliferation and differentiation potential in postnatal bone marrow and in umbilical cord blood opens up the possibility of using stem cells found in these tissues to treat degenerative, post-traumatic and hereditary diseases of the central nervous system. Copyright 2002 Wiley-Liss, Inc.

Neural control of the lips differs for young and older adults following a perturbation

PubMed Central

de Miranda Marzullo, Ana Carolina; Neto, Osmar Pinto; Ballard, Kirrie J.; Robin, Donald A.; Chaitow, Lauren

2011-01-01

Aging impairs the control of many skilled movements including speech. The purpose of this paper was to investigate whether young and older adults adapt to lower lip perturbations during speech differently. Twenty men (10 young, 26 ± 3 years of age; 10 older, 60 ± 9 years of age) were requested to repeat the word (“papa”) 300 times. In 15% of the trials, the subjects experienced a mechanical perturbation on the lower lip. Displacement and neural activation (EMG) of the upper and lower lips were evaluated. Perturbations to the lower lip caused a greater increase in the maximum displacement of the lower lip for older adults compared with young adults (34.7 ± 19% vs. 13.4 ± 17%; P = 0.017). Furthermore, young adults exhibited significantly greater 30–100 Hz normalized EMG power for the lower lip compared to the upper lip (P < 0.005). In young adults, changes from normal to perturbed trials in the 30–50 Hz frequency band of the EMG were negatively correlated to the changes from normal to perturbed trials in the lower lip maximum displacement (R2 = 0.48; P = 0.025). It is concluded that young adults adapt better to lower lip perturbations compared with older adults and that the associated neural activation strategy of the involved muscle is different for the two age groups. PMID:20852991

Evolution of Neural Networks for the Prediction of Hydraulic Conductivity as a Function of Borehole Geophysical Logs: Shobasama Site, Japan

NASA Astrophysics Data System (ADS)

Reeves, P.; McKenna, S. A.; Takeuchi, S.; Saegusa, H.

2003-12-01

In situ measurements of hydraulic conductivity in fractured rocks are expensive to acquire. Borehole geophysical measurements are relatively inexpensive to acquire but do not provide direct information on hydraulic conductivity. These geophysical measurements quantify properties of the rock that influence the hydraulic conductivity and it may be possible to employ a non-linear combination of these measurements to estimate hydraulic conductivity. Geophysical measurements collected in fractured granite at the Shobasama site in central Japan were used as the input to a feed-forward neural network. A simple genetic algorithm was used to simultaneously evolve the architecture and parameters of the neural network as well as determine an optimal subset of geophysical measurements for the prediction of hydraulic conductivity. The initial estimation procedure focused on predicting the class of the hydraulic conductivity, high, medium or low, from the geophysical measurements. This estimation was done while using the genetic algorithm to simultaneously determine the most important geophysical logs and optimize the architecture of the neural network. Results show that certain geophysical logs provide more information than others- most notably the short-normal resistivity, micro-resistivity, porosity and sonic logs provided the most information on hydraulic conductivity. The neural network produced excellent training results with accuracy of 90 percent or greater, but was unable to produce accurate predictions of the hydraulic conductivity class In the second phase of calculations, the selection of geophysical measurements is limited to only those that provide significant information. Additionally, this second phase predicts transmissivity instead of hydraulic conductivity in order to account for the differences in the length of the hydraulic test zones. Resulting predictions of transmissivity exhibit conditional bias with maximum prediction errors of three orders of magnitude occurring at the extreme measurement values. Results of these simulations indicate that the most informative geophysical measurements for the prediction of transmissivity are depth and sonic velocity. The long normal resistivity and self potential geophysical measurements are moderately informative. In addition, it was found that porosity and crack counts (clear, open, or hairline) do not inform predictions of transmissivity. This work was funded by the Japan Nuclear Cycle Development Institute. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy's National Nuclear Security Administration under contract DE-AC04-94-AL-85000

High-Throughput Analysis of Age-Dependent Protein Changes in Layer II/III of the Human Orbitofrontal Cortex

NASA Astrophysics Data System (ADS)

Kapadia, Fenika

Studies on the orbitofrontal cortex (OFC) during normal aging have shown a decline in cognitive functions, a loss of spines/synapses in layer III and gene expression changes related to neural communication. Biological changes during the course of normal aging are summarized into 9 hallmarks based on aging in peripheral tissue. Whether these hallmarks apply to non-dividing brain tissue is not known. Therefore, we opted to perform large-scale proteomic profiling of the OFC layer II/III during normal aging from 15 young and 18 old male subjects. MaxQuant was utilized for label-free quantification and statistical analysis by the Random Intercept Model (RIM) identified 118 differentially expressed (DE) age-related proteins. Altered neural communication was the most represented hallmark of aging (54% of DE proteins), highlighting the importance of communication in the brain. Functional analysis showed enrichment in GABA/glutamate signaling and pro-inflammatory responses. The former may contribute to alterations in excitation/inhibition, leading to cognitive decline during aging.

Neural control of renal tubular solute and water transport.

PubMed

DiBona, G F

1989-01-01

The neural control of renal tubular solute and water transport is recognized as an important physiological mechanism in the overall regulation of solute and water homeostasis by the mammalian organism. Recent studies have expanded the understanding of this mechanism concerning the transport of diverse solutes with beginning insight into the precise nature of the cellular transport processes involved. The modulatory roles of both circulating and intrarenal hormonal systems on the responses to alterations in the magnitude of efferent renal sympathetic nerve activity are being understood from the nerve terminal release of neurotransmitter to influences on cellular transport processes which determine the overall effect. When dietary sodium intake is normal or only modestly reduced, intact renal innervation is not essential for normal renal sodium conservation. However, when dietary sodium intake is severely restricted, there is maximum engagement of all mechanisms known to participate in renal sodium conservation and, under these conditions, intact renal innervation is essential for normal renal sodium conservation.

Use of transfer learning to detect diffuse degenerative hepatic diseases from ultrasound images in dogs: A methodological study.

PubMed

Banzato, T; Bonsembiante, F; Aresu, L; Gelain, M E; Burti, S; Zotti, A

2018-03-01

The aim of this methodological study was to develop a deep convolutional neural network (DNN) to detect degenerative hepatic disease from ultrasound images of the liver in dogs and to compare the diagnostic accuracy of the newly developed DNN with that of serum biochemistry and cytology on the same samples, using histopathology as a standard. Dogs with suspected hepatic disease that had no prior history of neoplastic disease, no hepatic nodular pathology, no ascites and ultrasonography performed 24h prior to death were included in the study (n=52). Ultrasonography and serum biochemistry were performed as part of the routine clinical evaluation. On the basis of histopathology, dogs were categorised as 'normal' (n=8), or having 'vascular abnormalities'(n=8), or 'inflammatory'(n=0), 'neoplastic' (n=4) or 'degenerative'(n=32) disease; dogs with 'neoplastic' disease were excluded from further analysis. On cytological evaluation, dogs were categorised as 'normal' (n=11), or having 'inflammatory' (n=0), 'neoplastic' (n=4) or 'degenerative' (n=37) disease. Dogs were categorised as having 'degenerative' (n=32) or 'non-degenerative' (n=16) liver disease for analysis due to the limited sample size. The DNN was developed using a transfer learning methodology on a pre-trained neural network that was retrained and fine-tuned to our data set. The resultant DNN had a high diagnostic accuracy for degenerative liver disease (area under the curve 0.91; sensitivity 100%; specificity 82.8%). Cytology and serum biochemical markers (alanine transaminase and aspartate transaminase) had poor diagnostic accuracy in the detection of degenerative liver disease. The DNN outperformed all the other non-invasive diagnostic tests in the detection of degenerative liver disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Conditional N-WASP knockout in mouse brain implicates actin cytoskeleton regulation in hydrocephalus pathology.

PubMed

Jain, Neeraj; Lim, Lee Wei; Tan, Wei Ting; George, Bhawana; Makeyev, Eugene; Thanabalu, Thirumaran

2014-04-01

Cerebrospinal fluid (CSF) is produced by the choroid plexus and moved by multi-ciliated ependymal cells through the ventricular system of the vertebrate brain. Defects in the ependymal layer functionality are a common cause of hydrocephalus. N-WASP (Neural-Wiskott Aldrich Syndrome Protein) is a brain-enriched regulator of actin cytoskeleton and N-WASP knockout caused embryonic lethality in mice with neural tube and cardiac abnormalities. To shed light on the role of N-WASP in mouse brain development, we generated N-WASP conditional knockout mouse model N-WASP(fl/fl); Nestin-Cre (NKO-Nes). NKO-Nes mice were born with Mendelian ratios but exhibited reduced growth characteristics compared to their littermates containing functional N-WASP alleles. Importantly, all NKO-Nes mice developed cranial deformities due to excessive CSF accumulation and did not survive past weaning. Coronal brain sections of these animals revealed dilated lateral ventricles, defects in ciliogenesis, loss of ependymal layer integrity, reduced thickness of cerebral cortex and aqueductal stenosis. Immunostaining for N-cadherin suggests that ependymal integrity in NKO-Nes mice is lost as compared to normal morphology in the wild-type controls. Moreover, scanning electron microscopy and immunofluorescence analyses of coronal brain sections with anti-acetylated tubulin antibodies revealed the absence of cilia in ventricular walls of NKO-Nes mice indicative of ciliogenesis defects. N-WASP deficiency does not lead to altered expression of N-WASP regulatory proteins, Fyn and Cdc42, which have been previously implicated in hydrocephalus pathology. Taken together, our results suggest that N-WASP plays a critical role in normal brain development and implicate actin cytoskeleton regulation as a vulnerable axis frequently deregulated in hydrocephalus. Copyright © 2014 Elsevier Inc. All rights reserved.

Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

NASA Astrophysics Data System (ADS)

Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

2017-03-01

Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

Evaluation of a new neutron energy spectrum unfolding code based on an Adaptive Neuro-Fuzzy Inference System (ANFIS).

PubMed

Hosseini, Seyed Abolfazl; Esmaili Paeen Afrakoti, Iman

2018-01-17

The purpose of the present study was to reconstruct the energy spectrum of a poly-energetic neutron source using an algorithm developed based on an Adaptive Neuro-Fuzzy Inference System (ANFIS). ANFIS is a kind of artificial neural network based on the Takagi-Sugeno fuzzy inference system. The ANFIS algorithm uses the advantages of both fuzzy inference systems and artificial neural networks to improve the effectiveness of algorithms in various applications such as modeling, control and classification. The neutron pulse height distributions used as input data in the training procedure for the ANFIS algorithm were obtained from the simulations performed by MCNPX-ESUT computational code (MCNPX-Energy engineering of Sharif University of Technology). Taking into account the normalization condition of each energy spectrum, 4300 neutron energy spectra were generated randomly. (The value in each bin was generated randomly, and finally a normalization of each generated energy spectrum was performed). The randomly generated neutron energy spectra were considered as output data of the developed ANFIS computational code in the training step. To calculate the neutron energy spectrum using conventional methods, an inverse problem with an approximately singular response matrix (with the determinant of the matrix close to zero) should be solved. The solution of the inverse problem using the conventional methods unfold neutron energy spectrum with low accuracy. Application of the iterative algorithms in the solution of such a problem, or utilizing the intelligent algorithms (in which there is no need to solve the problem), is usually preferred for unfolding of the energy spectrum. Therefore, the main reason for development of intelligent algorithms like ANFIS for unfolding of neutron energy spectra is to avoid solving the inverse problem. In the present study, the unfolded neutron energy spectra of 252Cf and 241Am-9Be neutron sources using the developed computational code were found to have excellent agreement with the reference data. Also, the unfolded energy spectra of the neutron sources as obtained using ANFIS were more accurate than the results reported from calculations performed using artificial neural networks in previously published papers. © The Author(s) 2018. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Neural plasticity of development and learning.

PubMed

Galván, Adriana

2010-06-01

Development and learning are powerful agents of change across the lifespan that induce robust structural and functional plasticity in neural systems. An unresolved question in developmental cognitive neuroscience is whether development and learning share the same neural mechanisms associated with experience-related neural plasticity. In this article, I outline the conceptual and practical challenges of this question, review insights gleaned from adult studies, and describe recent strides toward examining this topic across development using neuroimaging methods. I suggest that development and learning are not two completely separate constructs and instead, that they exist on a continuum. While progressive and regressive changes are central to both, the behavioral consequences associated with these changes are closely tied to the existing neural architecture of maturity of the system. Eventually, a deeper, more mechanistic understanding of neural plasticity will shed light on behavioral changes across development and, more broadly, about the underlying neural basis of cognition. (c) 2010 Wiley-Liss, Inc.

Different Effects of Hypoxia on Mental Rotation of Normal and Mirrored Letters: Evidence from the Rotation-Related Negativity.

PubMed

Ma, Qingguo; Hu, Linfeng; Li, Jiaojie; Hu, Yue; Xia, Ling; Chen, Xiaojian; Hu, Wendong

2016-01-01

The present study explored the neural mechanism underlying the effect of moderate and transient hypoxic exposure on mental rotation of two-dimensional letters in both normal and mirror versions. Event-related potential data and behavioral data were acquired in the task of discrimination between normal and mirrored versions separately in conditions of normoxia (simulated sea level) and hypoxia conditions (simulated 5000 meter altitude). The behavioral results revealed no significant difference between the normoxia and hypoxia conditions both in response time and error rate. However, obvious differences between these two conditions in ERP were found. First, enlarged P300 and Rotation-related Negativity (RRN) were observed in the hypoxia condition compared to the normoxia condition only with normal letters. Second, the angle effect on the amplitude of RRN was more evident with normal letters in the hypoxia condition than that in the normoxia condition. However, this angle effect nearly disappeared with the mirrored letters in the hypoxia condition. Third, more bilateral parietal activation was observed in the hypoxia condition than the normoxia condition. These results suggested that the compensation mechanism existed in the hypoxia condition and was effective with normal letters but had little effect on the mirrored letters. This study extends the research about the hypoxic effect on spatial ability of humans by employing a mental rotation task and further provides neural evidence for this effect.

Different Effects of Hypoxia on Mental Rotation of Normal and Mirrored Letters: Evidence from the Rotation-Related Negativity

PubMed Central

Ma, Qingguo; Hu, Linfeng; Li, Jiaojie; Hu, Yue; Xia, Ling; Chen, Xiaojian; Hu, Wendong

2016-01-01

The present study explored the neural mechanism underlying the effect of moderate and transient hypoxic exposure on mental rotation of two-dimensional letters in both normal and mirror versions. Event-related potential data and behavioral data were acquired in the task of discrimination between normal and mirrored versions separately in conditions of normoxia (simulated sea level) and hypoxia conditions (simulated 5000 meter altitude). The behavioral results revealed no significant difference between the normoxia and hypoxia conditions both in response time and error rate. However, obvious differences between these two conditions in ERP were found. First, enlarged P300 and Rotation-related Negativity (RRN) were observed in the hypoxia condition compared to the normoxia condition only with normal letters. Second, the angle effect on the amplitude of RRN was more evident with normal letters in the hypoxia condition than that in the normoxia condition. However, this angle effect nearly disappeared with the mirrored letters in the hypoxia condition. Third, more bilateral parietal activation was observed in the hypoxia condition than the normoxia condition. These results suggested that the compensation mechanism existed in the hypoxia condition and was effective with normal letters but had little effect on the mirrored letters. This study extends the research about the hypoxic effect on spatial ability of humans by employing a mental rotation task and further provides neural evidence for this effect. PMID:27144444

High-order tracking differentiator based adaptive neural control of a flexible air-breathing hypersonic vehicle subject to actuators constraints.

PubMed

Bu, Xiangwei; Wu, Xiaoyan; Tian, Mingyan; Huang, Jiaqi; Zhang, Rui; Ma, Zhen

2015-09-01

In this paper, an adaptive neural controller is exploited for a constrained flexible air-breathing hypersonic vehicle (FAHV) based on high-order tracking differentiator (HTD). By utilizing functional decomposition methodology, the dynamic model is reasonably decomposed into the respective velocity subsystem and altitude subsystem. For the velocity subsystem, a dynamic inversion based neural controller is constructed. By introducing the HTD to adaptively estimate the newly defined states generated in the process of model transformation, a novel neural based altitude controller that is quite simpler than the ones derived from back-stepping is addressed based on the normal output-feedback form instead of the strict-feedback formulation. Based on minimal-learning parameter scheme, only two neural networks with two adaptive parameters are needed for neural approximation. Especially, a novel auxiliary system is explored to deal with the problem of control inputs constraints. Finally, simulation results are presented to test the effectiveness of the proposed control strategy in the presence of system uncertainties and actuators constraints. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Effects of Dietary Protein and Fiber at Breakfast on Appetite, ad Libitum Energy Intake at Lunch, and Neural Responses to Visual Food Stimuli in Overweight Adults

PubMed Central

Sayer, R. Drew; Amankwaah, Akua F.; Tamer, Gregory G.; Chen, Ningning; Wright, Amy J.; Tregellas, Jason R.; Cornier, Marc-Andre; Kareken, David A.; Talavage, Thomas M.; McCrory, Megan A.; Campbell, Wayne W.

2016-01-01

Increasing either protein or fiber at mealtimes has relatively modest effects on ingestive behavior. Whether protein and fiber have additive or interactive effects on ingestive behavior is not known. Fifteen overweight adults (5 female, 10 male; BMI: 27.1 ± 0.2 kg/m2; aged 26 ± 1 year) consumed four breakfast meals in a randomized crossover manner (normal protein (12 g) + normal fiber (2 g), normal protein (12 g) + high fiber (8 g), high protein (25 g) + normal fiber (2 g), high protein (25 g) + high fiber (8 g)). The amount of protein and fiber consumed at breakfast did not influence postprandial appetite or ad libitum energy intake at lunch. In the fasting-state, visual food stimuli elicited significant responses in the bilateral insula and amygdala and left orbitofrontal cortex. Contrary to our hypotheses, postprandial right insula responses were lower after consuming normal protein vs. high protein breakfasts. Postprandial responses in other a priori brain regions were not significantly influenced by protein or fiber intake at breakfast. In conclusion, these data do not support increasing dietary protein and fiber at breakfast as effective strategies for modulating neural reward processing and acute ingestive behavior in overweight adults. PMID:26742068

Effects of Dietary Protein and Fiber at Breakfast on Appetite, ad Libitum Energy Intake at Lunch, and Neural Responses to Visual Food Stimuli in Overweight Adults.

PubMed

Sayer, R Drew; Amankwaah, Akua F; Tamer, Gregory G; Chen, Ningning; Wright, Amy J; Tregellas, Jason R; Cornier, Marc-Andre; Kareken, David A; Talavage, Thomas M; McCrory, Megan A; Campbell, Wayne W

2016-01-05

Increasing either protein or fiber at mealtimes has relatively modest effects on ingestive behavior. Whether protein and fiber have additive or interactive effects on ingestive behavior is not known. Fifteen overweight adults (5 female, 10 male; BMI: 27.1 ± 0.2 kg/m²; aged 26 ± 1 year) consumed four breakfast meals in a randomized crossover manner (normal protein (12 g) + normal fiber (2 g), normal protein (12 g) + high fiber (8 g), high protein (25 g) + normal fiber (2 g), high protein (25 g) + high fiber (8 g)). The amount of protein and fiber consumed at breakfast did not influence postprandial appetite or ad libitum energy intake at lunch. In the fasting-state, visual food stimuli elicited significant responses in the bilateral insula and amygdala and left orbitofrontal cortex. Contrary to our hypotheses, postprandial right insula responses were lower after consuming normal protein vs. high protein breakfasts. Postprandial responses in other a priori brain regions were not significantly influenced by protein or fiber intake at breakfast. In conclusion, these data do not support increasing dietary protein and fiber at breakfast as effective strategies for modulating neural reward processing and acute ingestive behavior in overweight adults.

Interactive learning in 2×2 normal form games by neural network agents

NASA Astrophysics Data System (ADS)

Spiliopoulos, Leonidas

2012-11-01

This paper models the learning process of populations of randomly rematched tabula rasa neural network (NN) agents playing randomly generated 2×2 normal form games of all strategic classes. This approach has greater external validity than the existing models in the literature, each of which is usually applicable to narrow subsets of classes of games (often a single game) and/or to fixed matching protocols. The learning prowess of NNs with hidden layers was impressive as they learned to play unique pure strategy equilibria with near certainty, adhered to principles of dominance and iterated dominance, and exhibited a preference for risk-dominant equilibria. In contrast, perceptron NNs were found to perform significantly worse than hidden layer NN agents and human subjects in experimental studies.

Potential energy surface interpolation with neural networks for instanton rate calculations

NASA Astrophysics Data System (ADS)

Cooper, April M.; Hallmen, Philipp P.; Kästner, Johannes

2018-03-01

Artificial neural networks are used to fit a potential energy surface (PES). We demonstrate the benefits of using not only energies but also their first and second derivatives as training data for the neural network. This ensures smooth and accurate Hessian surfaces, which are required for rate constant calculations using instanton theory. Our aim was a local, accurate fit rather than a global PES because instanton theory requires information on the potential only in the close vicinity of the main tunneling path. Elongations along vibrational normal modes at the transition state are used as coordinates for the neural network. The method is applied to the hydrogen abstraction reaction from methanol, calculated on a coupled-cluster level of theory. The reaction is essential in astrochemistry to explain the deuteration of methanol in the interstellar medium.

LavaNet—Neural network development environment in a general mine planning package

NASA Astrophysics Data System (ADS)

Kapageridis, Ioannis Konstantinou; Triantafyllou, A. G.

2011-04-01

LavaNet is a series of scripts written in Perl that gives access to a neural network simulation environment inside a general mine planning package. A well known and a very popular neural network development environment, the Stuttgart Neural Network Simulator, is used as the base for the development of neural networks. LavaNet runs inside VULCAN™—a complete mine planning package with advanced database, modelling and visualisation capabilities. LavaNet is taking advantage of VULCAN's Perl based scripting environment, Lava, to bring all the benefits of neural network development and application to geologists, mining engineers and other users of the specific mine planning package. LavaNet enables easy development of neural network training data sets using information from any of the data and model structures available, such as block models and drillhole databases. Neural networks can be trained inside VULCAN™ and the results be used to generate new models that can be visualised in 3D. Direct comparison of developed neural network models with conventional and geostatistical techniques is now possible within the same mine planning software package. LavaNet supports Radial Basis Function networks, Multi-Layer Perceptrons and Self-Organised Maps.

Congenital Amusia Persists in the Developing Brain after Daily Music Listening

PubMed Central

Mignault Goulet, Geneviève; Moreau, Patricia; Robitaille, Nicolas; Peretz, Isabelle

2012-01-01

Congenital amusia is a neurodevelopmental disorder that affects about 3% of the adult population. Adults experiencing this musical disorder in the absence of macroscopically visible brain injury are described as cases of congenital amusia under the assumption that the musical deficits have been present from birth. Here, we show that this disorder can be expressed in the developing brain. We found that (10–13 year-old) children exhibit a marked deficit in the detection of fine-grained pitch differences in both musical and acoustical context in comparison to their normally developing peers comparable in age and general intelligence. This behavioral deficit could be traced down to their abnormal P300 brain responses to the detection of subtle pitch changes. The altered pattern of electrical activity does not seem to arise from an anomalous functioning of the auditory cortex, because all early components of the brain potentials, the N100, the MMN, and the P200 appear normal. Rather, the brain and behavioral measures point to disrupted information propagation from the auditory cortex to other cortical regions. Furthermore, the behavioral and neural manifestations of the disorder remained unchanged after 4 weeks of daily musical listening. These results show that congenital amusia can be detected in childhood despite regular musical exposure and normal intellectual functioning. PMID:22606299

Language learning impairments: integrating basic science, technology, and remediation.

PubMed

Tallal, P; Merzenich, M M; Miller, S; Jenkins, W

1998-11-01

One of the fundamental goals of the modern field of neuroscience is to understand how neuronal activity gives rise to higher cortical function. However, to bridge the gap between neurobiology and behavior, we must understand higher cortical functions at the behavioral level at least as well as we have come to understand neurobiological processes at the cellular and molecular levels. This is certainly the case in the study of speech processing, where critical studies of behavioral dysfunction have provided key insights into the basic neurobiological mechanisms relevant to speech perception and production. Much of this progress derives from a detailed analysis of the sensory, perceptual, cognitive, and motor abilities of children who fail to acquire speech, language, and reading skills normally within the context of otherwise normal development. Current research now shows that a dysfunction in normal phonological processing, which is critical to the development of oral and written language, may derive, at least in part, from difficulties in perceiving and producing basic sensory-motor information in rapid succession--within tens of ms (see Tallal et al. 1993a for a review). There is now substantial evidence supporting the hypothesis that basic temporal integration processes play a fundamental role in establishing neural representations for the units of speech (phonemes), which must be segmented from the (continuous) speech stream and combined to form words, in order for the normal development of oral and written language to proceed. Results from magnetic resonance imaging (MRI) and positron emission tomography (PET) studies, as well as studies of behavioral performance in normal and language impaired children and adults, will be reviewed to support the view that the integration of rapidly changing successive acoustic events plays a primary role in phonological development and disorders. Finally, remediation studies based on this research, coupled with neuroplasticity research, will be presented.

Energy-Based Metrics for Arthroscopic Skills Assessment.

PubMed

Poursartip, Behnaz; LeBel, Marie-Eve; McCracken, Laura C; Escoto, Abelardo; Patel, Rajni V; Naish, Michael D; Trejos, Ana Luisa

2017-08-05

Minimally invasive skills assessment methods are essential in developing efficient surgical simulators and implementing consistent skills evaluation. Although numerous methods have been investigated in the literature, there is still a need to further improve the accuracy of surgical skills assessment. Energy expenditure can be an indication of motor skills proficiency. The goals of this study are to develop objective metrics based on energy expenditure, normalize these metrics, and investigate classifying trainees using these metrics. To this end, different forms of energy consisting of mechanical energy and work were considered and their values were divided by the related value of an ideal performance to develop normalized metrics. These metrics were used as inputs for various machine learning algorithms including support vector machines (SVM) and neural networks (NNs) for classification. The accuracy of the combination of the normalized energy-based metrics with these classifiers was evaluated through a leave-one-subject-out cross-validation. The proposed method was validated using 26 subjects at two experience levels (novices and experts) in three arthroscopic tasks. The results showed that there are statistically significant differences between novices and experts for almost all of the normalized energy-based metrics. The accuracy of classification using SVM and NN methods was between 70% and 95% for the various tasks. The results show that the normalized energy-based metrics and their combination with SVM and NN classifiers are capable of providing accurate classification of trainees. The assessment method proposed in this study can enhance surgical training by providing appropriate feedback to trainees about their level of expertise and can be used in the evaluation of proficiency.

Using personality neuroscience to study personality disorder.

PubMed

Abram, Samantha V; DeYoung, Colin G

2017-01-01

Personality neuroscience integrates techniques from personality psychology and neuroscience to elucidate the neural basis of individual differences in cognition, emotion, motivation, and behavior. This endeavor is pertinent not only to our understanding of healthy personality variation, but also to the aberrant trait manifestations present in personality disorders and severe psychopathology. In the current review, we focus on the advances and limitations of neuroimaging methods with respect to personality neuroscience. We discuss the value of personality theory as a means to link specific neural mechanisms with various traits (e.g., the neural basis of the "Big Five"). Given the overlap between dimensional models of normal personality and psychopathology, we also describe how researchers can reconceptualize psychopathological disorders along key dimensions, and, in turn, formulate specific neural hypotheses, extended from personality theory. Examples from the borderline personality disorder literature are used to illustrate this approach. We provide recommendations for utilizing neuroimaging methods to capture the neural mechanisms that underlie continuous traits across the spectrum from healthy to maladaptive. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Artificial neural networks for processing fluorescence spectroscopy data in skin cancer diagnostics

NASA Astrophysics Data System (ADS)

Lenhardt, L.; Zeković, I.; Dramićanin, T.; Dramićanin, M. D.

2013-11-01

Over the years various optical spectroscopic techniques have been widely used as diagnostic tools in the discrimination of many types of malignant diseases. Recently, synchronous fluorescent spectroscopy (SFS) coupled with chemometrics has been applied in cancer diagnostics. The SFS method involves simultaneous scanning of both emission and excitation wavelengths while keeping the interval of wavelengths (constant-wavelength mode) or frequencies (constant-energy mode) between them constant. This method is fast, relatively inexpensive, sensitive and non-invasive. Total synchronous fluorescence spectra of normal skin, nevus and melanoma samples were used as input for training of artificial neural networks. Two different types of artificial neural networks were trained, the self-organizing map and the feed-forward neural network. Histopathology results of investigated skin samples were used as the gold standard for network output. Based on the obtained classification success rate of neural networks, we concluded that both networks provided high sensitivity with classification errors between 2 and 4%.

Computing single step operators of logic programming in radial basis function neural networks

NASA Astrophysics Data System (ADS)

Hamadneh, Nawaf; Sathasivam, Saratha; Choon, Ong Hong

2014-07-01

Logic programming is the process that leads from an original formulation of a computing problem to executable programs. A normal logic program consists of a finite set of clauses. A valuation I of logic programming is a mapping from ground atoms to false or true. The single step operator of any logic programming is defined as a function (Tp:I→I). Logic programming is well-suited to building the artificial intelligence systems. In this study, we established a new technique to compute the single step operators of logic programming in the radial basis function neural networks. To do that, we proposed a new technique to generate the training data sets of single step operators. The training data sets are used to build the neural networks. We used the recurrent radial basis function neural networks to get to the steady state (the fixed point of the operators). To improve the performance of the neural networks, we used the particle swarm optimization algorithm to train the networks.

The amusic brain: in tune, out of key, and unaware.

PubMed

Peretz, Isabelle; Brattico, Elvira; Järvenpää, Miika; Tervaniemi, Mari

2009-05-01

Like language, music engagement is universal, complex and present early in life. However, approximately 4% of the general population experiences a lifelong deficit in music perception that cannot be explained by hearing loss, brain damage, intellectual deficiencies or lack of exposure. This musical disorder, commonly known as tone-deafness and now termed congenital amusia, affects mostly the melodic pitch dimension. Congenital amusia is hereditary and is associated with abnormal grey and white matter in the auditory cortex and the inferior frontal cortex. In order to relate these anatomical anomalies to the behavioural expression of the disorder, we measured the electrical brain activity of amusic subjects and matched controls while they monitored melodies for the presence of pitch anomalies. Contrary to current reports, we show that the amusic brain can track quarter-tone pitch differences, exhibiting an early right-lateralized negative brain response. This suggests near-normal neural processing of musical pitch incongruities in congenital amusia. It is important because it reveals that the amusic brain is equipped with the essential neural circuitry to perceive fine-grained pitch differences. What distinguishes the amusic from the normal brain is the limited awareness of this ability and the lack of responsiveness to the semitone changes that violate musical keys. These findings suggest that, in the amusic brain, the neural pitch representation cannot make contact with musical pitch knowledge along the auditory-frontal neural pathway.

Altered spontaneous neural activity in the occipital face area reflects behavioral deficits in developmental prosopagnosia.

PubMed

Zhao, Yuanfang; Li, Jingguang; Liu, Xiqin; Song, Yiying; Wang, Ruosi; Yang, Zetian; Liu, Jia

2016-08-01

Individuals with developmental prosopagnosia (DP) exhibit severe difficulties in recognizing faces and to a lesser extent, also exhibit difficulties in recognizing non-face objects. We used fMRI to investigate whether these behavioral deficits could be accounted for by altered spontaneous neural activity. Two aspects of spontaneous neural activity were measured: the intensity of neural activity in a voxel indexed by the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), and the connectivity of a voxel to neighboring voxels indexed by regional homogeneity (ReHo). Compared with normal adults, both the fALFF and ReHo values within the right occipital face area (rOFA) were significantly reduced in DP subjects. Follow-up studies on the normal adults revealed that these two measures indicated further functional division of labor within the rOFA. The fALFF in the rOFA was positively correlated with behavioral performance in recognition of non-face objects, whereas ReHo in the rOFA was positively correlated with processing of faces. When considered together, the altered fALFF and ReHo within the same region (rOFA) may account for the comorbid deficits in both face and object recognition in DPs, whereas the functional division of labor in these two measures helps to explain the relative independency of deficits in face recognition and object recognition in DP. Copyright © 2016 Elsevier Ltd. All rights reserved.

Podocalyxin Is a Novel Polysialylated Neural Adhesion Protein with Multiple Roles in Neural Development and Synapse Formation

PubMed Central

Vitureira, Nathalia; Andrés, Rosa; Pérez-Martínez, Esther; Martínez, Albert; Bribián, Ana; Blasi, Juan; Chelliah, Shierley; López-Doménech, Guillermo; De Castro, Fernando; Burgaya, Ferran; McNagny, Kelly; Soriano, Eduardo

2010-01-01

Neural development and plasticity are regulated by neural adhesion proteins, including the polysialylated form of NCAM (PSA-NCAM). Podocalyxin (PC) is a renal PSA-containing protein that has been reported to function as an anti-adhesin in kidney podocytes. Here we show that PC is widely expressed in neurons during neural development. Neural PC interacts with the ERM protein family, and with NHERF1/2 and RhoA/G. Experiments in vitro and phenotypic analyses of podxl-deficient mice indicate that PC is involved in neurite growth, branching and axonal fasciculation, and that PC loss-of-function reduces the number of synapses in the CNS and in the neuromuscular system. We also show that whereas some of the brain PC functions require PSA, others depend on PC per se. Our results show that PC, the second highly sialylated neural adhesion protein, plays multiple roles in neural development. PMID:20706633

Growth-related neural reorganization and the autism phenotype: a test of the hypothesis that altered brain growth leads to altered connectivity

PubMed Central

Lewis, John D.; Elman, Jeffrey L.

2009-01-01

Theoretical considerations, and findings from computational modeling, comparative neuroanatomy and developmental neuroscience, motivate the hypothesis that a deviant brain growth trajectory will lead to deviant patterns of change in cortico-cortical connectivity. Differences in brain size during development will alter the relative cost and effectiveness of short- and long-distance connections, and should thus impact the growth and retention of connections. Reduced brain size should favor long-distance connectivity; brain overgrowth should favor short-distance connectivity; and inconsistent deviations from the normal growth trajectory – as occurs in autism – should result in potentially disruptive changes to established patterns of functional and physical connectivity during development. To explore this hypothesis, neural networks which modeled inter-hemispheric interaction were grown at the rate of either typically developing children or children with autism. The influence of the length of the inter-hemispheric connections was analyzed at multiple developmental time-points. The networks that modeled autistic growth were less affected by removal of the inter-hemispheric connections than those that modeled normal growth – indicating a reduced reliance on long-distance connections – for short response times, and this difference increased substantially at approximately 24 simulated months of age. The performance of the networks showed a corresponding decline during development. And direct analysis of the connection weights showed a parallel reduction in connectivity. These modeling results support the hypothesis that the deviant growth trajectory in autism spectrum disorders may lead to a disruption of established patterns of functional connectivity during development, with potentially negative behavioral consequences, and a subsequent reduction in physical connectivity. The results are discussed in relation to the growing body of evidence of reduced functional and structural connectivity in autism, and in relation to the behavioral phenotype, particularly the developmental aspects. PMID:18171375

Brownian motion curve-based textural classification and its application in cancer diagnosis.

PubMed

Mookiah, Muthu Rama Krishnan; Shah, Pratik; Chakraborty, Chandan; Ray, Ajoy K

2011-06-01

To develop an automated diagnostic methodology based on textural features of the oral mucosal epithelium to discriminate normal and oral submucous fibrosis (OSF). A total of 83 normal and 29 OSF images from histopathologic sections of the oral mucosa are considered. The proposed diagnostic mechanism consists of two parts: feature extraction using Brownian motion curve (BMC) and design ofa suitable classifier. The discrimination ability of the features has been substantiated by statistical tests. An error back-propagation neural network (BPNN) is used to classify OSF vs. normal. In development of an automated oral cancer diagnostic module, BMC has played an important role in characterizing textural features of the oral images. Fisher's linear discriminant analysis yields 100% sensitivity and 85% specificity, whereas BPNN leads to 92.31% sensitivity and 100% specificity, respectively. In addition to intensity and morphology-based features, textural features are also very important, especially in histopathologic diagnosis of oral cancer. In view of this, a set of textural features are extracted using the BMC for the diagnosis of OSF. Finally, a textural classifier is designed using BPNN, which leads to a diagnostic performance with 96.43% accuracy. (Anal Quant

Normal development of human brain white matter from infancy to early adulthood: a diffusion tensor imaging study.

PubMed

Uda, Satoshi; Matsui, Mie; Tanaka, Chiaki; Uematsu, Akiko; Miura, Kayoko; Kawana, Izumi; Noguchi, Kyo

2015-01-01

Diffusion tensor imaging (DTI), which measures the magnitude of anisotropy of water diffusion in white matter, has recently been used to visualize and quantify parameters of neural tracts connecting brain regions. In order to investigate the developmental changes and sex and hemispheric differences of neural fibers in normal white matter, we used DTI to examine 52 healthy humans ranging in age from 2 months to 25 years. We extracted the following tracts of interest (TOIs) using the region of interest method: the corpus callosum (CC), cingulum hippocampus (CGH), inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF). We measured fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD). Approximate values and changes in growth rates of all DTI parameters at each age were calculated and analyzed using LOESS (locally weighted scatterplot smoothing). We found that for all TOIs, FA increased with age, whereas ADC, AD and RD values decreased with age. The turning point of growth rates was at approximately 6 years. FA in the CC was greater than that in the SLF, ILF and CGH. Moreover, FA, ADC and AD of the splenium of the CC (sCC) were greater than in the genu of the CC (gCC), whereas the RD of the sCC was lower than the RD of the gCC. The FA of right-hemisphere TOIs was significantly greater than that of left-hemisphere TOIs. In infants, growth rates of both FA and RD were larger than those of AD. Our data show that developmental patterns differ by TOIs and myelination along with the development of white matter, which can be mainly expressed as an increase in FA together with a decrease in RD. These findings clarify the long-term normal developmental characteristics of white matter microstructure from infancy to early adulthood. © 2015 S. Karger AG, Basel.

Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity.

PubMed

Sorg, Barbara A; Berretta, Sabina; Blacktop, Jordan M; Fawcett, James W; Kitagawa, Hiroshi; Kwok, Jessica C F; Miquel, Marta

2016-11-09

Perineuronal nets (PNNs) are unique extracellular matrix structures that wrap around certain neurons in the CNS during development and control plasticity in the adult CNS. They appear to contribute to a wide range of diseases/disorders of the brain, are involved in recovery from spinal cord injury, and are altered during aging, learning and memory, and after exposure to drugs of abuse. Here the focus is on how a major component of PNNs, chondroitin sulfate proteoglycans, control plasticity, and on the role of PNNs in memory in normal aging, in a tauopathy model of Alzheimer's disease, and in drug addiction. Also discussed is how altered extracellular matrix/PNN formation during development may produce synaptic pathology associated with schizophrenia, bipolar disorder, major depression, and autism spectrum disorders. Understanding the molecular underpinnings of how PNNs are altered in normal physiology and disease will offer insights into new treatment approaches for these diseases. Copyright © 2016 the authors 0270-6474/16/3611459-10$15.00/0.

Detection of retinal changes from illumination normalized fundus images using convolutional neural networks

NASA Astrophysics Data System (ADS)

Adal, Kedir M.; van Etten, Peter G.; Martinez, Jose P.; Rouwen, Kenneth; Vermeer, Koenraad A.; van Vliet, Lucas J.

2017-03-01

Automated detection and quantification of spatio-temporal retinal changes is an important step to objectively assess disease progression and treatment effects for dynamic retinal diseases such as diabetic retinopathy (DR). However, detecting retinal changes caused by early DR lesions such as microaneurysms and dot hemorrhages from longitudinal pairs of fundus images is challenging due to intra and inter-image illumination variation between fundus images. This paper explores a method for automated detection of retinal changes from illumination normalized fundus images using a deep convolutional neural network (CNN), and compares its performance with two other CNNs trained separately on color and green channel fundus images. Illumination variation was addressed by correcting for the variability in the luminosity and contrast estimated from a large scale retinal regions. The CNN models were trained and evaluated on image patches extracted from a registered fundus image set collected from 51 diabetic eyes that were screened at two different time-points. The results show that using normalized images yield better performance than color and green channel images, suggesting that illumination normalization greatly facilitates CNNs to quickly and correctly learn distinctive local image features of DR related retinal changes.

Design and simulation of optoelectronic complementary dual neural elements for realizing a family of normalized vector 'equivalence-nonequivalence' operations

NASA Astrophysics Data System (ADS)

Krasilenko, Vladimir G.; Nikolsky, Aleksandr I.; Lazarev, Alexander A.; Magas, Taras E.

2010-04-01

Equivalence models (EM) advantages of neural networks (NN) are shown in paper. EMs are based on vectormatrix procedures with basic operations of continuous neurologic: normalized vector operations "equivalence", "nonequivalence", "autoequivalence", "autononequivalence". The capacity of NN on the basis of EM and of its modifications, including auto-and heteroassociative memories for 2D images, exceeds in several times quantity of neurons. Such neuroparadigms are very perspective for processing, recognition, storing large size and strongly correlated images. A family of "normalized equivalence-nonequivalence" neuro-fuzzy logic operations on the based of generalized operations fuzzy-negation, t-norm and s-norm is elaborated. A biologically motivated concept and time pulse encoding principles of continuous logic photocurrent reflexions and sample-storage devices with pulse-width photoconverters have allowed us to design generalized structures for realization of the family of normalized linear vector operations "equivalence"-"nonequivalence". Simulation results show, that processing time in such circuits does not exceed units of micro seconds. Circuits are simple, have low supply voltage (1-3 V), low power consumption (milliwatts), low levels of input signals (microwatts), integrated construction, satisfy the problem of interconnections and cascading.

Decreased levels of embryonic retinoic acid synthesis accelerate recovery from arterial growth delay in a mouse model of DiGeorge syndrome.

PubMed

Ryckebüsch, Lucile; Bertrand, Nicolas; Mesbah, Karim; Bajolle, Fanny; Niederreither, Karen; Kelly, Robert G; Zaffran, Stéphane

2010-03-05

Loss of Tbx1 and decrease of retinoic acid (RA) synthesis result in DiGeorge/velocardiofacial syndrome (DGS/VCFS)-like phenotypes in mouse models, including defects in septation of the outflow tract of the heart and anomalies of pharyngeal arch-derived structures including arteries of the head and neck, laryngeal-tracheal cartilage, and thymus/parathyroid. Wild-type levels of T-box transcription factor (Tbx)1 and RA signaling are required for normal pharyngeal arch artery development. Recent studies have shown that reduction of RA or loss of Tbx1 alters the contribution of second heart field (SHF) progenitor cells to the elongating heart tube. Here we tested whether Tbx1 and the RA signaling pathway interact during the deployment of the SHF and formation of the mature aortic arch. Molecular markers of the SHF, neural crest and smooth muscle cells, were analyzed in Raldh2;Tbx1 compound heterozygous mutants. Our results revealed that the SHF and outflow tract develop normally in Raldh2(+/-);Tbx1(+/-) embryos. However, we found that decreased levels of RA accelerate the recovery from arterial growth delay observed in Tbx1(+/-) mutant embryos. This compensation coincides with the differentiation of smooth muscle cells in the 4th pharyngeal arch arteries, and is associated with severity of neural crest cell migration defects observed in these mutants. Our data suggest that differences in levels of embryonic RA may contribute to the variability in great artery anomalies observed in DGS/VCFS patients.

Dehydration-Anorexia Derives From A Reduction In Meal Size, But Not Meal Number

PubMed Central

Boyle, Christina N.; Lorenzen, Sarah M.; Compton, Douglas; Watts, Alan G.

2011-01-01

The anorexia that results from extended periods of cellular dehydration is an important physiological adaptation that limits the intake of osmolytes from food and helps maintain the integrity of fluid compartments. The ability to experimentally control both the development and reversal of anorexia, together with the understanding of underlying hormonal and neuropeptidergic signals, make dehydration (DE)-anorexia a powerful model for exploring the interactions of neural networks that stimulate and inhibit food intake. However, it is not known which meal parameters are affected by cellular dehydration to generate anorexia. Here we use continuous and high temporal resolution recording of food and fluid intake, together with a drinking-explicit method of meal pattern analysis to explore which meal parameters are modified during DE-anorexia. We find that the most important factor responsible for DE-anorexia is the failure to maintain feeding behavior once a meal has started, rather than the ability to initiate a meal, which remains virtually intact. This outcome is consistent with increased sensitivity to satiation signals and post-prandial satiety mechanisms. We also find that DE-anorexia significantly disrupts the temporal distribution of meals across the day so that the number of nocturnal meals gradually decreases while diurnal meal number increases. Surprisingly, once DE-anorexia is reversed this temporal redistribution is maintained for at least 4 days after normal food intake has resumed, which may allow increased daily food intake even after normal satiety mechanisms are reinstated. Therefore, DE-anorexia apparently develops from a selective targeting of those neural networks that control meal termination, whereas meal initiation mechanisms remain viable. PMID:21854794

Towards a miniaturized brain-machine-spinal cord interface (BMSI) for restoration of function after spinal cord injury.

PubMed

Shahdoost, Shahab; Frost, Shawn; Van Acker, Gustaf; DeJong, Stacey; Dunham, Caleb; Barbay, Scott; Nudo, Randolph; Mohseni, Pedram

2014-01-01

Nearly 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress towards developing a miniaturized brain-machine-spinal cord interface (BMSI) that is envisioned to convert in real time the neural command signals recorded from the brain to electrical stimuli delivered to the spinal cord below the injury level. Specifically, the paper reports on a corticospinal interface integrated circuit (IC) as a core building block for such a BMSI that is capable of low-noise recording of extracellular neural spikes from the cerebral cortex as well as muscle activation using intraspinal microstimulation (ISMS) in a rat with contusion injury to the thoracic spinal cord. The paper further presents results from a neurobiological study conducted in both normal and SCI rats to investigate the effect of various ISMS parameters on movement thresholds in the rat hindlimb. Coupled with proper signal-processing algorithms in the future for the transformation between the cortically recorded data and ISMS parameters, such a BMSI has the potential to facilitate functional recovery after an SCI by re-establishing corticospinal communication channels lost due to the injury.

Conditionally immortalized stem cell lines from human spinal cord retain regional identity and generate functional V2a interneurons and motorneurons.

PubMed

Cocks, Graham; Romanyuk, Nataliya; Amemori, Takashi; Jendelova, Pavla; Forostyak, Oksana; Jeffries, Aaron R; Perfect, Leo; Thuret, Sandrine; Dayanithi, Govindan; Sykova, Eva; Price, Jack

2013-06-07

The use of immortalized neural stem cells either as models of neural development in vitro or as cellular therapies in central nervous system (CNS) disorders has been controversial. This controversy has centered on the capacity of immortalized cells to retain characteristic features of the progenitor cells resident in the tissue of origin from which they were derived, and the potential for tumorogenicity as a result of immortalization. Here, we report the generation of conditionally immortalized neural stem cell lines from human fetal spinal cord tissue, which addresses these issues. Clonal neural stem cell lines were derived from 10-week-old human fetal spinal cord and conditionally immortalized with an inducible form of cMyc. The derived lines were karyotyped, transcriptionally profiled by microarray, and assessed against a panel of spinal cord progenitor markers with immunocytochemistry. In addition, the lines were differentiated and assessed for the presence of neuronal fate markers and functional calcium channels. Finally, a clonal line expressing eGFP was grafted into lesioned rat spinal cord and assessed for survival, differentiation characteristics, and tumorogenicity. We demonstrate that these clonal lines (a) retain a clear transcriptional signature of ventral spinal cord progenitors and a normal karyotype after extensive propagation in vitro, (b) differentiate into relevant ventral neuronal subtypes with functional T-, L-, N-, and P/Q-type Ca(2+) channels and spontaneous calcium oscillations, and (c) stably engraft into lesioned rat spinal cord without tumorogenicity. We propose that these cells represent a useful tool both for the in vitro study of differentiation into ventral spinal cord neuronal subtypes, and for examining the potential of conditionally immortalized neural stem cells to facilitate functional recovery after spinal cord injury or disease.

Function of FEZF1 during early neural differentiation of human embryonic stem cells.

PubMed

Liu, Xin; Su, Pei; Lu, Lisha; Feng, Zicen; Wang, Hongtao; Zhou, Jiaxi

2018-01-01

The understanding of the mechanism underlying human neural development has been hampered due to lack of a cellular system and complicated ethical issues. Human embryonic stem cells (hESCs) provide an invaluable model for dissecting human development because of unlimited self-renewal and the capacity to differentiate into nearly all cell types in the human body. In this study, using a chemical defined neural induction protocol and molecular profiling, we identified Fez family zinc finger 1 (FEZF1) as a potential regulator of early human neural development. FEZF1 is rapidly up-regulated during neural differentiation in hESCs and expressed before PAX6, a well-established marker of early human neural induction. We generated FEZF1-knockout H1 hESC lines using CRISPR-CAS9 technology and found that depletion of FEZF1 abrogates neural differentiation of hESCs. Moreover, loss of FEZF1 impairs the pluripotency exit of hESCs during neural specification, which partially explains the neural induction defect caused by FEZF1 deletion. However, enforced expression of FEZF1 itself fails to drive neural differentiation in hESCs, suggesting that FEZF1 is necessary but not sufficient for neural differentiation from hESCs. Taken together, our findings identify one of the earliest regulators expressed upon neural induction and provide insight into early neural development in human.

Real-time antenna fault diagnosis experiments at DSS 13

NASA Technical Reports Server (NTRS)

Mellstrom, J.; Pierson, C.; Smyth, P.

1992-01-01

Experimental results obtained when a previously described fault diagnosis system was run online in real time at the 34-m beam waveguide antenna at Deep Space Station (DSS) 13 are described. Experimental conditions and the quality of results are described. A neural network model and a maximum-likelihood Gaussian classifier are compared with and without a Markov component to model temporal context. At the rate of a state update every 6.4 seconds, over a period of roughly 1 hour, the neural-Markov system had zero errors (incorrect state estimates) while monitoring both faulty and normal operations. The overall results indicate that the neural-Markov combination is the most accurate model and has significant practical potential.

Heparanase 2, mutated in urofacial syndrome, mediates peripheral neural development in Xenopus

PubMed Central

Roberts, Neil A.; Woolf, Adrian S.; Stuart, Helen M.; Thuret, Raphaël; McKenzie, Edward A.; Newman, William G.; Hilton, Emma N.

2014-01-01

Urofacial syndrome (UFS; previously Ochoa syndrome) is an autosomal recessive disease characterized by incomplete bladder emptying during micturition. This is associated with a dyssynergia in which the urethral walls contract at the same time as the detrusor smooth muscle in the body of the bladder. UFS is also characterized by an abnormal facial expression upon smiling, and bilateral weakness in the distribution of the facial nerve has been reported. Biallelic mutations in HPSE2 occur in UFS. This gene encodes heparanase 2, a protein which inhibits the activity of heparanase. Here, we demonstrate, for the first time, an in vivo developmental role for heparanase 2. We identified the Xenopus orthologue of heparanase 2 and showed that the protein is localized to the embryonic ventrolateral neural tube where motor neurons arise. Morpholino-induced loss of heparanase 2 caused embryonic skeletal muscle paralysis, and morphant motor neurons had aberrant morphology including less linear paths and less compactly-bundled axons than normal. Biochemical analyses demonstrated that loss of heparanase 2 led to upregulation of fibroblast growth factor 2/phosphorylated extracellular signal-related kinase signalling and to alterations in levels of transcripts encoding neural- and muscle-associated molecules. Thus, a key role of heparanase 2 is to buffer growth factor signalling in motor neuron development. These results shed light on the pathogenic mechanisms underpinning the clinical features of UFS and support the contention that congenital peripheral neuropathy is a key feature of this disorder. PMID:24691552

The downregulation of Wnt/β-catenin signaling pathway is associated with zinc deficiency-induced proliferative deficit of C17.2 neural stem cells.

PubMed

Zhao, Jianya; Han, Jingling; Jiang, Junkang; Shi, Shangshi; Ma, Xia; Liu, Xinhang; Wang, Cheng; Nie, Xiaoke; He, Yunhua; Jiang, Shengyang; Wan, Chunhua

2015-07-30

Zinc is an essential nutrient that is important for normal brain development. Zinc deficiency has been linked to aberrant neurological development and functioning. However, the molecular mechanisms underlying Zinc deficiency-induced neurological disorders remain largely elusive. In the present study, we showed that the proliferation of C17.2 neural stem cells (NSCs) was evidently impaired after exposed to low levels of Zinc chelator, N,N,N',N'-tetrakis-(2-pyridylmethy) ethylenediamine (TPEN). In addition, we found that TPEN-induced proliferative deficit of NSCs was related with significant downregulation of Wnt/β-catenin signaling. Zinc deficiency impaired the proliferation of neural stem cells in dose- and time-dependent manners. Western blot revealed that the levels of p-Ser9-glycogensynthase kinase-3β (p-GSK-3β) and β-catenin were remarkably downregulated during TPEN-induced C17.2 proliferative impairment. Moreover, immunofluorescent analysis indicated that the level of nuclear β-catenin was apparently decreased following TPEN exposure. Furthermore, application with GSK-3β inhibitor lithium chloride (LiCl) reversed TPEN-induced downregulation of β-catenin and impairment of cell proliferation. Flow cytometry analysis also showed that TPEN-induced impairment of NSC proliferation could be reversed by LiCl. Taken together, these findings suggested that the disturbance of canonical Wnt/β-catenin signaling pathway partially accounted for Zinc deficiency-induced proliferative impairment of NSCs. Copyright © 2015 Elsevier B.V. All rights reserved.

Morphogenesis of the mouse neural plate depends on distinct roles of cofilin 1 in apical and basal epithelial domains

PubMed Central

Grego-Bessa, Joaquim; Hildebrand, Jeffrey; Anderson, Kathryn V.

2015-01-01

The genetic control of mammalian epithelial polarity and dynamics can be studied in vivo at cellular resolution during morphogenesis of the mouse neural tube. The mouse neural plate is a simple epithelium that is transformed into a columnar pseudostratified tube over the course of ∼24 h. Apical F-actin is known to be important for neural tube closure, but the precise roles of actin dynamics in the neural epithelium are not known. To determine how the organization of the neural epithelium and neural tube closure are affected when actin dynamics are blocked, we examined the cellular basis of the neural tube closure defect in mouse mutants that lack the actin-severing protein cofilin 1 (CFL1). Although apical localization of the adherens junctions, the Par complex, the Crumbs complex and SHROOM3 is normal in the mutants, CFL1 has at least two distinct functions in the apical and basal domains of the neural plate. Apically, in the absence of CFL1 myosin light chain does not become phosphorylated, indicating that CFL1 is required for the activation of apical actomyosin required for neural tube closure. On the basal side of the neural plate, loss of CFL1 has the opposite effect on myosin: excess F-actin and myosin accumulate and the ectopic myosin light chain is phosphorylated. The basal accumulation of F-actin is associated with the assembly of ectopic basal tight junctions and focal disruptions of the basement membrane, which eventually lead to a breakdown of epithelial organization. PMID:25742799

Cartilaginous development of the human craniovertebral junction as visualised by a new three-dimensional computer reconstruction technique.

PubMed

David, K M; McLachlan, J C; Aiton, J F; Whiten, S C; Smart, S D; Thorogood, P V; Crockard, H A

1998-02-01

Serial transverse histological sections of the human craniovertebral junction (CVJ) of 4 normal human embryos (aged 45 to 58 d) and of a fetus (77 d) were used to create 3-dimensional computer models of the CVJ. The main components modelled included the chondrified basioccipital, atlas and axis, notochord, the vertebrobasilar complex and the spinal cord. Chondrification of the component parts of CVJ had already begun at 45 d (Stage 18). The odontoid process appeared to develop from a short eminence of the axis forming a third occipital condyle with the caudal end of the basioccipital. The cartilaginous anterior arch of C1 appeared at 50-53 d (Stages 20-21). Neural arches of C1 and C2 showed gradual closure, but there was still a wide posterior spina bifida in the oldest reconstructed specimen (77 d fetus). The position of the notochord was constant throughout. The normal course of the vertebral arteries was already established and the chondrified vertebral foramina showed progressive closure. The findings confirm that the odontoid process is not derived solely from the centrum of C1 and that there is a 'natural basilar invagination' of C2 during normal embryonic development. On the basis of the observed shape and developmental pattern of structures of the cartilaginous human CVJ, we suggest that certain pathologies are likely to originate during the chondrification phase of development.

Adult Human Gingival Epithelial Cells as a Source for Whole-tooth Bioengineering

PubMed Central

Angelova Volponi, A.; Kawasaki, M.; Sharpe, P.T.

2013-01-01

Teeth develop from interactions between embryonic oral epithelium and neural-crest-derived mesenchyme. These cells can be separated into single-cell populations and recombined to form normal teeth, providing a basis for bioengineering new teeth if suitable, non-embryonic cell sources can be identified. We show here that cells can be isolated from adult human gingival tissue that can be expanded in vitro and, when combined with mouse embryonic tooth mesenchyme cells, form teeth. Teeth with developing roots can be produced from this cell combination following transplantation into renal capsules. These bioengineered teeth contain dentin and enamel with ameloblast-like cells and rests of Malassez of human origin. PMID:23458883

Biphasic influence of Miz1 on neural crest development by regulating cell survival and apical adhesion complex formation in the developing neural tube

PubMed Central

Kerosuo, Laura; Bronner, Marianne E.

2014-01-01

Myc interacting zinc finger protein-1 (Miz1) is a transcription factor known to regulate cell cycle– and cell adhesion–related genes in cancer. Here we show that Miz1 also plays a critical role in neural crest development. In the chick, Miz1 is expressed throughout the neural plate and closing neural tube. Its morpholino-mediated knockdown affects neural crest precursor survival, leading to reduction of neural plate border and neural crest specifier genes Msx-1, Pax7, FoxD3, and Sox10. Of interest, Miz1 loss also causes marked reduction of adhesion molecules (N-cadherin, cadherin6B, and α1-catenin) with a concomitant increase of E-cadherin in the neural folds, likely leading to delayed and decreased neural crest emigration. Conversely, Miz1 overexpression results in up-regulation of cadherin6B and FoxD3 expression in the neural folds/neural tube, leading to premature neural crest emigration and increased number of migratory crest cells. Although Miz1 loss effects cell survival and proliferation throughout the neural plate, the neural progenitor marker Sox2 was unaffected, suggesting a neural crest–selective effect. The results suggest that Miz1 is important not only for survival of neural crest precursors, but also for maintenance of integrity of the neural folds and tube, via correct formation of the apical adhesion complex therein. PMID:24307680

Prenatal testosterone and gender-related behaviour.

PubMed

Hines, Melissa

2006-11-01

Testosterone plays an important role in mammalian brain development. In neural regions with appropriate receptors testosterone, or its metabolites, influences patterns of cell death and survival, neural connectivity and neurochemical characterization. Consequently, testosterone exposure during critical periods of early development produces permanent behavioural changes. In humans, affected behaviours include childhood play behaviour, sexual orientation, core gender identity and other characteristics that show sex differences (i.e. differ on average between males and females). These influences have been demonstrated primarily in individuals who experienced marked prenatal hormone abnormalities and associated ambiguities of genital development (e.g. congenital adrenal hyperplasia). However, there is also evidence that testosterone works within the normal range to make some individuals within each sex more sex-typical than others. The size of testosterone-related influences, and perhaps even their existence, varies from one sex-typed characteristic to another. For instance: prenatal exposure to high levels of testosterone has a substantial influence on sex-typical play behaviour, including sex-typed toy preferences, whereas influences on core gender identify and sexual orientation are less dramatic. In addition: there appears to be little or no influence of prenatal testosterone on mental rotations ability, although mental rotations ability shows a marked sex difference. These findings have implications for basic understanding of the role of testosterone in normative gender development, as well as for the clinical management of individuals with disorders of sex development (formerly called intersex syndromes).

Selective Roles of Normal and Mutant Huntingtin in Neural Induction and Early Neurogenesis

PubMed Central

Nguyen, Giang D.; Gokhan, Solen; Molero, Aldrin E.; Mehler, Mark F.

2013-01-01

Huntington's disease (HD) is a neurodegenerative disorder caused by abnormal polyglutamine expansion in the amino-terminal end of the huntingtin protein (Htt) and characterized by progressive striatal and cortical pathology. Previous reports have shown that Htt is essential for embryogenesis, and a recent study by our group revealed that the pathogenic form of Htt (mHtt) causes impairments in multiple stages of striatal development. In this study, we have examined whether HD-associated striatal developmental deficits are reflective of earlier maturational alterations occurring at the time of neurulation by assessing differential roles of Htt and mHtt during neural induction and early neurogenesis using an in vitro mouse embryonic stem cell (ESC) clonal assay system. We demonstrated that the loss of Htt in ESCs (KO ESCs) severely disrupts the specification of primitive and definitive neural stem cells (pNSCs, dNSCs, respectively) during the process of neural induction. In addition, clonally derived KO pNSCs and dNSCs displayed impaired proliferative potential, enhanced cell death and altered multi-lineage potential. Conversely, as observed in HD knock-in ESCs (Q111 ESCs), mHtt enhanced the number and size of pNSC clones, which exhibited enhanced proliferative potential and precocious neuronal differentiation. The transition from Q111 pNSCs to fibroblast growth factor 2 (FGF2)-responsive dNSCs was marked by potentiation in the number of dNSCs and altered proliferative potential. The multi-lineage potential of Q111 dNSCs was also enhanced with precocious neurogenesis and oligodendrocyte progenitor elaboration. The generation of Q111 epidermal growth factor (EGF)-responsive dNSCs was also compromised, whereas their multi-lineage potential was unaltered. These abnormalities in neural induction were associated with differential alterations in the expression profiles of Notch, Hes1 and Hes5. These cumulative observations indicate that Htt is required for multiple stages of neural induction, whereas mHtt enhances this process and promotes precocious neurogenesis and oligodendrocyte progenitor cell elaboration. PMID:23691206

A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development

PubMed Central

Ciarlo, Christie; Kaufman, Charles K; Kinikoglu, Beste; Michael, Jonathan; Yang, Song; D′Amato, Christopher; Blokzijl-Franke, Sasja; den Hertog, Jeroen; Schlaeger, Thorsten M; Zhou, Yi; Liao, Eric

2017-01-01

The neural crest is a dynamic progenitor cell population that arises at the border of neural and non-neural ectoderm. The inductive roles of FGF, Wnt, and BMP at the neural plate border are well established, but the signals required for subsequent neural crest development remain poorly characterized. Here, we conducted a screen in primary zebrafish embryo cultures for chemicals that disrupt neural crest development, as read out by crestin:EGFP expression. We found that the natural product caffeic acid phenethyl ester (CAPE) disrupts neural crest gene expression, migration, and melanocytic differentiation by reducing Sox10 activity. CAPE inhibits FGF-stimulated PI3K/Akt signaling, and neural crest defects in CAPE-treated embryos are suppressed by constitutively active Akt1. Inhibition of Akt activity by constitutively active PTEN similarly decreases crestin expression and Sox10 activity. Our study has identified Akt as a novel intracellular pathway required for neural crest differentiation. PMID:28832322

Use of deep neural network ensembles to identify embryonic-fetal transition markers: repression of COX7A1 in embryonic and cancer cells

PubMed Central

West, Michael D.; Labat, Ivan; Sternberg, Hal; Larocca, Dana; Nasonkin, Igor; Chapman, Karen B.; Singh, Ratnesh; Makarev, Eugene; Aliper, Alex; Kazennov, Andrey; Alekseenko, Andrey; Shuvalov, Nikolai; Cheskidova, Evgenia; Alekseev, Aleksandr; Artemov, Artem; Putin, Evgeny; Mamoshina, Polina; Pryanichnikov, Nikita; Larocca, Jacob; Copeland, Karen; Izumchenko, Evgeny; Korzinkin, Mikhail; Zhavoronkov, Alex

2018-01-01

Here we present the application of deep neural network (DNN) ensembles trained on transcriptomic data to identify the novel markers associated with the mammalian embryonic-fetal transition (EFT). Molecular markers of this process could provide important insights into regulatory mechanisms of normal development, epimorphic tissue regeneration and cancer. Subsequent analysis of the most significant genes behind the DNNs classifier on an independent dataset of adult-derived and human embryonic stem cell (hESC)-derived progenitor cell lines led to the identification of COX7A1 gene as a potential EFT marker. COX7A1, encoding a cytochrome C oxidase subunit, was up-regulated in post-EFT murine and human cells including adult stem cells, but was not expressed in pre-EFT pluripotent embryonic stem cells or their in vitro-derived progeny. COX7A1 expression level was observed to be undetectable or low in multiple sarcoma and carcinoma cell lines as compared to normal controls. The knockout of the gene in mice led to a marked glycolytic shift reminiscent of the Warburg effect that occurs in cancer cells. The DNN approach facilitated the elucidation of a potentially new biomarker of cancer and pre-EFT cells, the embryo-onco phenotype, which may potentially be used as a target for controlling the embryonic-fetal transition. PMID:29487692

Use of deep neural network ensembles to identify embryonic-fetal transition markers: repression of COX7A1 in embryonic and cancer cells.

PubMed

West, Michael D; Labat, Ivan; Sternberg, Hal; Larocca, Dana; Nasonkin, Igor; Chapman, Karen B; Singh, Ratnesh; Makarev, Eugene; Aliper, Alex; Kazennov, Andrey; Alekseenko, Andrey; Shuvalov, Nikolai; Cheskidova, Evgenia; Alekseev, Aleksandr; Artemov, Artem; Putin, Evgeny; Mamoshina, Polina; Pryanichnikov, Nikita; Larocca, Jacob; Copeland, Karen; Izumchenko, Evgeny; Korzinkin, Mikhail; Zhavoronkov, Alex

2018-01-30

Here we present the application of deep neural network (DNN) ensembles trained on transcriptomic data to identify the novel markers associated with the mammalian embryonic-fetal transition (EFT). Molecular markers of this process could provide important insights into regulatory mechanisms of normal development, epimorphic tissue regeneration and cancer. Subsequent analysis of the most significant genes behind the DNNs classifier on an independent dataset of adult-derived and human embryonic stem cell (hESC)-derived progenitor cell lines led to the identification of COX7A1 gene as a potential EFT marker. COX7A1 , encoding a cytochrome C oxidase subunit, was up-regulated in post-EFT murine and human cells including adult stem cells, but was not expressed in pre-EFT pluripotent embryonic stem cells or their in vitro -derived progeny. COX7A1 expression level was observed to be undetectable or low in multiple sarcoma and carcinoma cell lines as compared to normal controls. The knockout of the gene in mice led to a marked glycolytic shift reminiscent of the Warburg effect that occurs in cancer cells. The DNN approach facilitated the elucidation of a potentially new biomarker of cancer and pre-EFT cells, the embryo-onco phenotype, which may potentially be used as a target for controlling the embryonic-fetal transition.

Key Clinical Factors Predicting Adipokine and Oxidative Stress Marker Concentrations among Normal, Overweight and Obese Pregnant Women Using Artificial Neural Networks.

PubMed

Solis-Paredes, Mario; Estrada-Gutierrez, Guadalupe; Perichart-Perera, Otilia; Montoya-Estrada, Araceli; Guzmán-Huerta, Mario; Borboa-Olivares, Héctor; Bravo-Flores, Eyerahi; Cardona-Pérez, Arturo; Zaga-Clavellina, Veronica; Garcia-Latorre, Ethel; Gonzalez-Perez, Gabriela; Hernández-Pérez, José Alfredo; Irles, Claudine

2017-12-28

Maternal obesity has been related to adverse neonatal outcomes and fetal programming. Oxidative stress and adipokines are potential biomarkers in such pregnancies; thus, the measurement of these molecules has been considered critical. Therefore, we developed artificial neural network (ANN) models based on maternal weight status and clinical data to predict reliable maternal blood concentrations of these biomarkers at the end of pregnancy. Adipokines (adiponectin, leptin, and resistin), and DNA, lipid and protein oxidative markers (8-oxo-2'-deoxyguanosine, malondialdehyde and carbonylated proteins, respectively) were assessed in blood of normal weight, overweight and obese women in the third trimester of pregnancy. A Back-propagation algorithm was used to train ANN models with four input variables (age, pre-gestational body mass index (p-BMI), weight status and gestational age). ANN models were able to accurately predict all biomarkers with regression coefficients greater than R² = 0.945. P-BMI was the most significant variable for estimating adiponectin and carbonylated proteins concentrations (37%), while gestational age was the most relevant variable to predict resistin and malondialdehyde (34%). Age, gestational age and p-BMI had the same significance for leptin values. Finally, for 8-oxo-2'-deoxyguanosine prediction, the most significant variable was age (37%). These models become relevant to improve clinical and nutrition interventions in prenatal care.

Cephalometric landmark detection in dental x-ray images using convolutional neural networks

NASA Astrophysics Data System (ADS)

Lee, Hansang; Park, Minseok; Kim, Junmo

2017-03-01

In dental X-ray images, an accurate detection of cephalometric landmarks plays an important role in clinical diagnosis, treatment and surgical decisions for dental problems. In this work, we propose an end-to-end deep learning system for cephalometric landmark detection in dental X-ray images, using convolutional neural networks (CNN). For detecting 19 cephalometric landmarks in dental X-ray images, we develop a detection system using CNN-based coordinate-wise regression systems. By viewing x- and y-coordinates of all landmarks as 38 independent variables, multiple CNN-based regression systems are constructed to predict the coordinate variables from input X-ray images. First, each coordinate variable is normalized by the length of either height or width of an image. For each normalized coordinate variable, a CNN-based regression system is trained on training images and corresponding coordinate variable, which is a variable to be regressed. We train 38 regression systems with the same CNN structure on coordinate variables, respectively. Finally, we compute 38 coordinate variables with these trained systems from unseen images and extract 19 landmarks by pairing the regressed coordinates. In experiments, the public database from the Grand Challenges in Dental X-ray Image Analysis in ISBI 2015 was used and the proposed system showed promising performance by successfully locating the cephalometric landmarks within considerable margins from the ground truths.

Neural correlates of genetically abnormal social cognition in Williams syndrome.

PubMed

Meyer-Lindenberg, Andreas; Hariri, Ahmad R; Munoz, Karen E; Mervis, Carolyn B; Mattay, Venkata S; Morris, Colleen A; Berman, Karen Faith

2005-08-01

Williams-Beuren syndrome (WBS), caused by a microdeletion of approximately 21 genes on chromosome 7q11.23, is characterized by unique hypersociability combined with increased non-social anxiety. Using functional neuroimaging, we found reduced amygdala activation in individuals with WBS for threatening faces but increased activation for threatening scenes, relative to matched normal controls. Activation and interactions of prefrontal regions linked to amygdala, especially orbitofrontal cortex, were abnormal, suggesting a genetically controlled neural circuitry for regulating human social behavior.

Using chaotic artificial neural networks to model memory in the brain

NASA Astrophysics Data System (ADS)

Aram, Zainab; Jafari, Sajad; Ma, Jun; Sprott, Julien C.; Zendehrouh, Sareh; Pham, Viet-Thanh

2017-03-01

In the current study, a novel model for human memory is proposed based on the chaotic dynamics of artificial neural networks. This new model explains a biological fact about memory which is not yet explained by any other model: There are theories that the brain normally works in a chaotic mode, while during attention it shows ordered behavior. This model uses the periodic windows observed in a previously proposed model for the brain to store and then recollect the information.

Calcium signaling mediates five types of cell morphological changes to form neural rosettes.

PubMed

Hříbková, Hana; Grabiec, Marta; Klemová, Dobromila; Slaninová, Iva; Sun, Yuh-Man

2018-02-12

Neural rosette formation is a critical morphogenetic process during neural development, whereby neural stem cells are enclosed in rosette niches to equipoise proliferation and differentiation. How neural rosettes form and provide a regulatory micro-environment remains to be elucidated. We employed the human embryonic stem cell-based neural rosette system to investigate the structural development and function of neural rosettes. Our study shows that neural rosette formation consists of five types of morphological change: intercalation, constriction, polarization, elongation and lumen formation. Ca 2+ signaling plays a pivotal role in the five steps by regulating the actions of the cytoskeletal complexes, actin, myosin II and tubulin during intercalation, constriction and elongation. These, in turn, control the polarizing elements, ZO-1, PARD3 and β-catenin during polarization and lumen production for neural rosette formation. We further demonstrate that the dismantlement of neural rosettes, mediated by the destruction of cytoskeletal elements, promotes neurogenesis and astrogenesis prematurely, indicating that an intact rosette structure is essential for orderly neural development. © 2018. Published by The Company of Biologists Ltd.

Fluid and flexible minds: Intelligence reflects synchrony in the brain’s intrinsic network architecture

PubMed Central

Ferguson, Michael A.; Anderson, Jeffrey S.; Spreng, R. Nathan

2017-01-01

Human intelligence has been conceptualized as a complex system of dissociable cognitive processes, yet studies investigating the neural basis of intelligence have typically emphasized the contributions of discrete brain regions or, more recently, of specific networks of functionally connected regions. Here we take a broader, systems perspective in order to investigate whether intelligence is an emergent property of synchrony within the brain’s intrinsic network architecture. Using a large sample of resting-state fMRI and cognitive data (n = 830), we report that the synchrony of functional interactions within and across distributed brain networks reliably predicts fluid and flexible intellectual functioning. By adopting a whole-brain, systems-level approach, we were able to reliably predict individual differences in human intelligence by characterizing features of the brain’s intrinsic network architecture. These findings hold promise for the eventual development of neural markers to predict changes in intellectual function that are associated with neurodevelopment, normal aging, and brain disease.

The brain’s conversation with itself: neural substrates of dialogic inner speech

PubMed Central

Weis, Susanne; McCarthy-Jones, Simon; Moseley, Peter; Smailes, David; Fernyhough, Charles

2016-01-01

Inner speech has been implicated in important aspects of normal and atypical cognition, including the development of auditory hallucinations. Studies to date have focused on covert speech elicited by simple word or sentence repetition, while ignoring richer and arguably more psychologically significant varieties of inner speech. This study compared neural activation for inner speech involving conversations (‘dialogic inner speech’) with single-speaker scenarios (‘monologic inner speech’). Inner speech-related activation differences were then compared with activations relating to Theory-of-Mind (ToM) reasoning and visual perspective-taking in a conjunction design. Generation of dialogic (compared with monologic) scenarios was associated with a widespread bilateral network including left and right superior temporal gyri, precuneus, posterior cingulate and left inferior and medial frontal gyri. Activation associated with dialogic scenarios and ToM reasoning overlapped in areas of right posterior temporal cortex previously linked to mental state representation. Implications for understanding verbal cognition in typical and atypical populations are discussed. PMID:26197805

Prenatal neurogenesis in autism spectrum disorders

NASA Astrophysics Data System (ADS)

Kaushik, Gaurav; Zarbalis, Konstantinos

2016-03-01

An ever-increasing body of literature describes compelling evidence that a subset of young children on the autism spectrum show abnormal cerebral growth trajectories. In these cases, normal cerebral size at birth is followed by a period of abnormal growth and starting in late childhood often by regression compared to unaffected controls. Recent work has demonstrated an abnormal increase in the number of neurons of the prefrontal cortex suggesting that cerebral size increase in autism is driven by excess neuronal production. In addition, some affected children display patches of abnormal laminar positioning of cortical projection neurons. As both cortical projection neuron numbers and their correct layering within the developing cortex requires the undisturbed proliferation of neural progenitors, it appears that neural progenitors lie in the center of the autism pathology associated with early brain overgrowth. Consequently, autism spectrum disorders associated with cerebral enlargement should be viewed as birth defects of an early embryonic origin with profound implications for their early diagnosis, preventive strategies, and therapeutic intervention.

Loss of autophagy in pro-opiomelanocortin neurons perturbs axon growth and causes metabolic dysregulation.

PubMed

Coupé, Bérengère; Ishii, Yuko; Dietrich, Marcelo O; Komatsu, Masaaki; Horvath, Tamas L; Bouret, Sebastien G

2012-02-08

The hypothalamic melanocortin system, which includes neurons that produce pro-opiomelanocortin (POMC)-derived peptides, is a major negative regulator of energy balance. POMC neurons begin to acquire their unique properties during neonatal life. The formation of functional neural systems requires massive cytoplasmic remodeling that may involve autophagy, an important intracellular mechanism for the degradation of damaged proteins and organelles. Here we investigated the functional and structural effects of the deletion of an essential autophagy gene, Atg7, in POMC neurons. Lack of Atg7 in POMC neurons caused higher postweaning body weight, increased adiposity, and glucose intolerance. These metabolic impairments were associated with an age-dependent accumulation of ubiquitin/p62-positive aggregates in the hypothalamus and a disruption in the maturation of POMC-containing axonal projections. Together, these data provide direct genetic evidence that Atg7 in POMC neurons is required for normal metabolic regulation and neural development, and they implicate hypothalamic autophagy deficiency in the pathogenesis of obesity. Copyright © 2012 Elsevier Inc. All rights reserved.

Application of neural based estimation algorithm for gait phases of above knee prosthesis.

PubMed

Tileylioğlu, E; Yilmaz, A

2015-01-01

In this study, two gait phase estimation methods which utilize a rule based quantization and an artificial neural network model respectively are developed and applied for the microcontroller based semi-active knee prosthesis in order to respond user demands and adapt environmental conditions. In this context, an experimental environment in which gait data collected synchronously from both inertial and image based measurement systems has been set up. The inertial measurement system that incorporates MEM accelerometers and gyroscopes is used to perform direct motion measurement through the microcontroller, while the image based measurement system is employed for producing the verification data and assessing the success of the prosthesis. Embedded algorithms dynamically normalize the input data prior to gait phase estimation. The real time analyses of two methods revealed that embedded ANN based approach performs slightly better in comparison with the rule based algorithm and has advantage of being easily-scalable, thus able to accommodate additional input parameters considering the microcontroller constraints.

A sub-1-volt analog metal oxide memristive-based synaptic device with large conductance change for energy-efficient spike-based computing systems

NASA Astrophysics Data System (ADS)

Hsieh, Cheng-Chih; Roy, Anupam; Chang, Yao-Feng; Shahrjerdi, Davood; Banerjee, Sanjay K.

2016-11-01

Nanoscale metal oxide memristors have potential in the development of brain-inspired computing systems that are scalable and efficient. In such systems, memristors represent the native electronic analogues of the biological synapses. In this work, we show cerium oxide based bilayer memristors that are forming-free, low-voltage (˜|0.8 V|), energy-efficient (full on/off switching at ˜8 pJ with 20 ns pulses, intermediate states switching at ˜fJ), and reliable. Furthermore, pulse measurements reveal the analog nature of the memristive device; that is, it can directly be programmed to intermediate resistance states. Leveraging this finding, we demonstrate spike-timing-dependent plasticity, a spike-based Hebbian learning rule. In those experiments, the memristor exhibits a marked change in the normalized synaptic strength (>30 times), when the pre- and post-synaptic neural spikes overlap. This demonstration is an important step towards the physical construction of high density and high connectivity neural networks.

Loss of Autophagy in Proopiomelanocortin Neurons Perturbs Axon Growth and Causes Metabolic Dysregulation

PubMed Central

Coupé, Bérengère; Ishii, Yuko; Dietrich, Marcelo O; Komatsu, Masaaki; Horvath, Tamas L.; Bouret, Sebastien G.

2012-01-01

Summary The hypothalamic melanocortin system, which includes neurons that produce proopiomelanocortin (POMC)-derived peptides, is a major negative regulator of energy balance. POMC neurons begin to acquire their unique properties during neonatal life. The formation of functional neural systems requires massive cytoplasmic remodeling that may involve autophagy, an important intracellular mechanism for the degradation of damaged proteins and organelles. Here we investigated the functional and structural effects of the deletion of an essential autophagy gene, Atg7, in POMC neurons. Lack of Atg7 in POMC neurons caused higher post-weaning body weight, increased adiposity, and glucose intolerance. These metabolic impairments were associated with an age-dependant accumulation of ubiquitin/p62-positive aggregates in the hypothalamus and a disruption in the maturation of POMC-containing axonal projections. Together, these data provide direct genetic evidence that Atg7 in POMC neurons is required for normal metabolic regulation and neural development, and they implicate hypothalamic autophagy deficiency in the pathogenesis of obesity. PMID:22285542

Radial basis function neural networks in non-destructive determination of compound aspirin tablets on NIR spectroscopy.

PubMed

Dou, Ying; Mi, Hong; Zhao, Lingzhi; Ren, Yuqiu; Ren, Yulin

2006-09-01

The application of the second most popular artificial neural networks (ANNs), namely, the radial basis function (RBF) networks, has been developed for quantitative analysis of drugs during the last decade. In this paper, the two components (aspirin and phenacetin) were simultaneously determined in compound aspirin tablets by using near-infrared (NIR) spectroscopy and RBF networks. The total database was randomly divided into a training set (50) and a testing set (17). Different preprocessing methods (standard normal variate (SNV), multiplicative scatter correction (MSC), first-derivative and second-derivative) were applied to two sets of NIR spectra of compound aspirin tablets with different concentrations of two active components and compared each other. After that, the performance of RBF learning algorithm adopted the nearest neighbor clustering algorithm (NNCA) and the criterion for selection used a cross-validation technique. Results show that using RBF networks to quantificationally analyze tablets is reliable, and the best RBF model was obtained by first-derivative spectra.

Neuronal activity during development: permissive or instructive?

PubMed

Crair, M C

1999-02-01

Experimental studies over the past year have shown that neural activity has a range of effects on the development of neural pathways. Although activity appears unimportant for establishing many aspects of the gross morphology and topology of the brain, there are many cases where the presence of neural activity is essential for the formation of a mature system of neural connections; in some instances, the pattern of neural activity actually orchestrates the final arrangement of neural connections.

Two States Mapping Based Time Series Neural Network Model for Compensation Prediction Residual Error

NASA Astrophysics Data System (ADS)

Jung, Insung; Koo, Lockjo; Wang, Gi-Nam

2008-11-01

The objective of this paper was to design a model of human bio signal data prediction system for decreasing of prediction error using two states mapping based time series neural network BP (back-propagation) model. Normally, a lot of the industry has been applied neural network model by training them in a supervised manner with the error back-propagation algorithm for time series prediction systems. However, it still has got a residual error between real value and prediction result. Therefore, we designed two states of neural network model for compensation residual error which is possible to use in the prevention of sudden death and metabolic syndrome disease such as hypertension disease and obesity. We determined that most of the simulation cases were satisfied by the two states mapping based time series prediction model. In particular, small sample size of times series were more accurate than the standard MLP model.