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Sample records for high cortical spreading

  1. Cortical spreading depression: An enigma

    NASA Astrophysics Data System (ADS)

    Miura, R. M.; Huang, H.; Wylie, J. J.

    2007-08-01

    The brain is a complex organ with active components composed largely of neurons, glial cells, and blood vessels. There exists an enormous experimental and theoretical literature on the mechanisms involved in the functioning of the brain, but we still do not have a good understanding of how it works on a gross mechanistic level. In general, the brain maintains a homeostatic state with relatively small ion concentration changes, the major ions being sodium, potassium, and chloride. Calcium ions are present in smaller quantities but still play an important role in many phenomena. Cortical spreading depression (CSD for short) was discovered over 60 years ago by A.A.P. Leão, a Brazilian physiologist doing his doctoral research on epilepsy at Harvard University, “Spreading depression of activity in the cerebral cortex," J. Neurophysiol., 7 (1944), pp. 359-390. Cortical spreading depression is characterized by massive changes in ionic concentrations and slow nonlinear chemical waves, with speeds on the order of mm/min, in the cortex of different brain structures in various experimental animals. In humans, CSD is associated with migraine with aura, where a light scintillation in the visual field propagates, then disappears, and is followed by a sustained headache. To date, CSD remains an enigma, and further detailed experimental and theoretical investigations are needed to develop a comprehensive picture of the diverse mechanisms involved in producing CSD. A number of mechanisms have been hypothesized to be important for CSD wave propagation. In this paper, we briefly describe several characteristics of CSD wave propagation, and examine some of the mechanisms that are believed to be important, including ion diffusion, membrane ionic currents, osmotic effects, spatial buffering, neurotransmitter substances, gap junctions, metabolic pumps, and synaptic connections. Continuum models of CSD, consisting of coupled nonlinear diffusion equations for the ion concentrations, and

  2. Distinct vascular conduction with cortical spreading depression.

    PubMed

    Brennan, Kevin C; Beltrán-Parrazal, Luis; López-Valdés, Hector E; Theriot, Jeremy; Toga, Arthur W; Charles, Andrew C

    2007-06-01

    Cortical spreading depression (CSD) is associated with significant vasodilatation and vasoconstriction, but the relationship between the cortical parenchymal and vascular phenomena remains poorly understood. We used optical intrinsic signal (OIS) imaging and electrophysiology to simultaneously examine the vascular and parenchymal changes that occur with CSD in anesthetized mice and rats. CSD was associated with a propagated multiphasic change in optical reflectance, with correlated negative DC shift in field potential. Dilatation of cortical surface arterioles propagated with a significantly greater intrinsic velocity than the parenchymal CSD wavefront measured by OIS and electrophysiology. Dilatation traveled in a circuitous pattern along individual arterioles, indicating specific vascular conduction as opposed to concentric propagation of a parenchymal signal. Arteriolar dilatation propagated into areas beyond the spread of parenchymal OIS and electrophysiological changes of CSD. Conversely, vasomotor activity could be experimentally dissociated from the parenchymal CSD wave. Frequent repetitive CSD evoked by continuous stimulation was associated with a reduced or absent arteriolar response despite preserved parenchymal OIS and electrophysiological changes. Similarly, dimethylsulfoxide at high concentrations (10%) inhibited arteriolar reactivity despite preserved parenchymal OIS and electrophysiological changes. These results suggest a mechanism, intrinsic to the vasculature, for propagation of vasodilatation associated with CSD. Distinct vascular conduction could be important for the pathogenesis of conditions that involve CSD, including migraine, stroke, and traumatic brain injury.

  3. Vagus nerve stimulation inhibits cortical spreading depression.

    PubMed

    Chen, Shih-Pin; Ay, Ilknur; de Morais, Andreia Lopes; Qin, Tao; Zheng, Yi; Sadeghian, Homa; Oka, Fumiaki; Simon, Bruce; Eikermann-Haerter, Katharina; Ayata, Cenk

    2016-04-01

    Vagus nerve stimulation has recently been reported to improve symptoms of migraine. Cortical spreading depression is the electrophysiological event underlying migraine aura and is a trigger for headache. We tested whether vagus nerve stimulation inhibits cortical spreading depression to explain its antimigraine effect. Unilateral vagus nerve stimulation was delivered either noninvasively through the skin or directly by electrodes placed around the nerve. Systemic physiology was monitored throughout the study. Both noninvasive transcutaneous and invasive direct vagus nerve stimulations significantly suppressed spreading depression susceptibility in the occipital cortex in rats. The electrical stimulation threshold to evoke a spreading depression was elevated by more than 2-fold, the frequency of spreading depressions during continuous topical 1 M KCl was reduced by ∼40%, and propagation speed of spreading depression was reduced by ∼15%. This effect developed within 30 minutes after vagus nerve stimulation and persisted for more than 3 hours. Noninvasive transcutaneous vagus nerve stimulation was as efficacious as direct invasive vagus nerve stimulation, and the efficacy did not differ between the ipsilateral and contralateral hemispheres. Our findings provide a potential mechanism by which vagus nerve stimulation may be efficacious in migraine and suggest that susceptibility to spreading depression is a suitable platform to optimize its efficacy.

  4. Cortical spreading depression-induced preconditioning in the brain

    PubMed Central

    Shen, Ping-ping; Hou, Shuai; Ma, Di; Zhao, Ming-ming; Zhu, Ming-qin; Zhang, Jing-dian; Feng, Liang-shu; Cui, Li; Feng, Jia-chun

    2016-01-01

    Cortical spreading depression is a technique used to depolarize neurons. During focal or global ischemia, cortical spreading depression-induced preconditioning can enhance tolerance of further injury. However, the underlying mechanism for this phenomenon remains relatively unclear. To date, numerous issues exist regarding the experimental model used to precondition the brain with cortical spreading depression, such as the administration route, concentration of potassium chloride, induction time, duration of the protection provided by the treatment, the regional distribution of the protective effect, and the types of neurons responsible for the greater tolerance. In this review, we focus on the mechanisms underlying cortical spreading depression-induced tolerance in the brain, considering excitatory neurotransmission and metabolism, nitric oxide, genomic reprogramming, inflammation, neurotropic factors, and cellular stress response. Specifically, we clarify the procedures and detailed information regarding cortical spreading depression-induced preconditioning and build a foundation for more comprehensive investigations in the field of neural regeneration and clinical application in the future. PMID:28123433

  5. [Cortical spreading depolarization: a new pathophysiological mechanism in neurological diseases].

    PubMed

    Sánchez-Porras, Renán; Robles-Cabrera, Adriana; Santos, Edgar

    2014-05-20

    Cortical spreading depolarization is a wave of almost complete depolarization of the neuronal and glial cells that occurs in different neurological diseases such as migraine with aura, subarachnoid hemorrhage, intracerebral hemorrhage, head trauma and stroke. These depolarization waves are characterized by a change in the negative potential with an amplitude between -10 and -30mV, duration of ∼1min and changes in the ion homeostasis between the intra- and extracellular space. This results in neuronal edema and dendritic distortion. Under pathologic states of hypoperfusion, cortical spreading depolarization can produce oxidative stress, worsen hypoxia and induce neuronal death. This is due to intense arterial vasoconstriction produced by an inverse response called spreading ischemia. Only in the last years there has been an electrophysiological confirmation of cortical spreading depolarization in human brains. Occurrence of cortical spreading depolarization has been associated with worse outcome in patients. Currently, increased knowledge regarding the pathophysiologic mechanisms supports the hypothetical correlation of cortical spreading depolarization with brain damage in humans. There are diverse therapeutic alternatives that promise inhibition of cortical spreading depolarization and subsequent better outcomes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  6. Cortical spreading depression impairs oxygen delivery and metabolism in mice.

    PubMed

    Yuzawa, Izumi; Sakadžić, Sava; Srinivasan, Vivek J; Shin, Hwa Kyoung; Eikermann-Haerter, Katharina; Boas, David A; Ayata, Cenk

    2012-02-01

    Cortical spreading depression (CSD) is associated with severe hypoperfusion in mice. Using minimally invasive multimodal optical imaging, we show that severe flow reductions during and after spreading depression are associated with a steep decline in cerebral metabolic rate of oxygen. Concurrent severe hemoglobin desaturation suggests that the oxygen metabolism becomes at least in part supply limited, and the decrease in cortical blood volume implicates vasoconstriction as the mechanism. In support of oxygen supply-demand mismatch, cortical nicotinamide adenine dinucleotide (NADH) fluorescence increases during spreading depression for at least 5 minutes, particularly away from parenchymal arterioles. However, modeling of tissue oxygen delivery shows that cerebral metabolic rate of oxygen drops more than predicted by a purely supply-limited model, raising the possibility of a concurrent reduction in oxygen demand during spreading depression. Importantly, a subsequent spreading depression triggered within 15 minutes evokes a monophasic flow increase superimposed on the oligemic baseline, which markedly differs from the response to the preceding spreading depression triggered in naive cortex. Altogether, these data suggest that CSD is associated with long-lasting oxygen supply-demand mismatch linked to severe vasoconstriction in mice.

  7. Regulation of cerebral metabolism during cortical spreading depression

    PubMed Central

    Feuerstein, Delphine; Gramer, Markus; Takagaki, Masatoshi; Gabel, Paula; Kumagai, Tetsuya; Graf, Rudolf

    2015-01-01

    We analyzed the metabolic response to cortical spreading depression that drastically increases local energy demand to restore ion homeostasis. During single and multiple cortical spreading depressions in the rat cortex, we simultaneously monitored extracellular levels of glucose and lactate using rapid sampling microdialysis and glucose influx using 18 F-fluorodeoxyglucose positron emission tomography while tracking cortical spreading depression using laser speckle imaging. Combining the acquired data with steady-state requirements we developed a mass-conserving compartment model including neurons and glia that was consistent with the observed data. In summary, our findings are: (1) Early breakdown of glial glycogen provides a major source of energy during increased energy demand and leaves 80% of blood-borne glucose to neurons. (2) Lactate is used solely by neurons and only if extracellular lactate levels are >80% above normal. (3) Although the ratio of oxygen and glucose consumption transiently reaches levels <3, the major part (>90%) of the overall energy supply is from oxidative metabolism. (4) During cortical spreading depression, brain release of lactate exceeds its consumption suggesting that lactate is only a circumstantial energy substrate. Our findings provide a general scenario for the metabolic response to increased cerebral energy demand. PMID:26661217

  8. Role of astrocyte connexin hemichannels in cortical spreading depression.

    PubMed

    Rovegno, Maximiliano; Sáez, Juan C

    2017-08-29

    Cortical spreading depression (CSD) is an intriguing phenomenon consisting of massive slow brain depolarizations that affects neurons and glial cells. It has been recognized since 1944, but its pathogenesis has only been uncovered during the last decade. Acute brain injuries can be further complicated by CSD in more than 50% of severe cases. This phenomenon is repetitive and produces a metabolic overload that increments secondary damage. Propagation of CSD is known to be linked to excitotoxicity, but the mechanisms associated with its initiation remain less understood. It has been shown that CSD can be initiated by increases in extracellular [K(+)] ([K(+)]e), and animal models use high [K(+)]e to promote CSD. Connexin hemichannel activity increases due to high [K(+)]e and low extracellular [Ca(2+)], conditions that occur after brain injury. Moreover, glial cell gap junction channels are fundamental in controlling extracellular medium composition, particularly in maintaining normal glutamate and [K(+)]e levels through "spatial buffering". However, the role of astrocytic gap junctions under tissue stress can change to damage spread in the acute damage zone whereas the reduced communication in adjacent zone would reduce cell dead propagation. Here, we review the main findings associated with CSD, and discuss the possible involvement of astrocytic connexin-based channels in secondary damage propagation. Copyright © 2017. Published by Elsevier B.V.

  9. Cortico-cortical evoked potentials for sites of early versus late seizure spread in stereoelectroencephalography.

    PubMed

    Lega, Bradley; Dionisio, Sasha; Flanigan, Patrick; Bingaman, William; Najm, Imad; Nair, Dileep; Gonzalez-Martinez, Jorge

    2015-09-01

    Cortico-cortical evoked potentials offer the possibility of understanding connectivity within seizure networks to improve diagnosis and more accurately identify candidates for seizure surgery. We sought to determine if cortico-cortical evoked potentials and post-stimulation oscillatory changes differ for sites of EARLY versus LATE ictal spread. 37 patients undergoing stereoelectroencephalography were tested using a cortico-cortical evoked potential paradigm. All electrodes were classified according to the speed of ictal spread. EARLY spread sites were matched to a LATE spread site equidistant from the onset zone. Root-mean-square was used to quantify evoked responses and post-stimulation gamma band power and coherence were extracted and compared. Sites of EARLY spread exhibited significantly greater evoked responses after stimulation across all patients (t(36)=2.973, p=0.004). Stimulation elicited enhanced gamma band activity at EARLY spread sites (t(36)=2.61, p=0.03, FDR corrected); this gamma band oscillation was highly coherent with the onset zone. Cortico-cortical evoked potentials and post-stimulation changes in gamma band activity differ between sites of EARLY versus LATE ictal spread. The oscillatory changes can help visualize connectivity within the seizure network.

  10. Cortical spreading depression occurs during elective neurosurgical procedures.

    PubMed

    Carlson, Andrew P; William Shuttleworth, C; Mead, Brittany; Burlbaw, Brittany; Krasberg, Mark; Yonas, Howard

    2017-01-01

    OBJECTIVE Cortical spreading depression (CSD) has been observed with relatively high frequency in the period following human brain injury, including traumatic brain injury and ischemic/hemorrhagic stroke. These events are characterized by loss of ionic gradients through massive cellular depolarization, neuronal dysfunction (depression of electrocorticographic [ECoG] activity) and slow spread (2-5 mm/min) across the cortical surface. Previous data obtained in animals have suggested that even in the absence of underlying injury, neurosurgical manipulation can induce CSD and could potentially be a modifiable factor in neurosurgical injury. The authors report their initial experience with direct intraoperative ECoG monitoring for CSD. METHODS The authors prospectively enrolled patients undergoing elective craniotomy for supratentorial lesions in cases in which the surgical procedure was expected to last > 2 hours. These patients were monitored for CSD from the time of dural opening through the time of dural closure, using a standard 1 × 6 platinum electrode coupled with an AC or full-spectrum DC amplifier. The data were processed using standard techniques to evaluate for slow potential changes coupled with suppression of high-frequency ECoG propagating across the electrodes. Data were compared with CSD validated in previous intensive care unit (ICU) studies, to evaluate recording conditions most likely to permit CSD detection, and identify likely events during the course of neurosurgical procedures using standard criteria. RESULTS Eleven patients underwent ECoG monitoring during elective neurosurgical procedures. During the periods of monitoring, 2 definite CSDs were observed to occur in 1 patient and 8 suspicious events were detected in 4 patients. In other patients, either no events were observed or artifact limited interpretation of the data. The DC-coupled amplifier system represented an improvement in stability of data compared with AC-coupled systems. Compared

  11. Spreading depression and focal venous cerebral ischemia enhance cortical neurogenesis

    PubMed Central

    Tamaki, Ryo; Orie, Samuel Ige; Alessandri, Beat; Kempski, Oliver; Heimann, Axel

    2017-01-01

    Endogenous neurogenesis can arise from a variety of physiological stimuli including exercise, learning, or “enriched environment” as well as pathological conditions such as ischemia, epilepsy or cortical spreading depression. Whether all these conditions use a common trigger to set off endogenous neurogenesis is yet unclear. We hypothesized that cortical spreading depression (CSD) induces neurogenesis in the cerebral cortex and dentate gyrus after cerebral venous ischemia. Forty-two Wistar rats alternatively underwent sham operation (Sham), induction of ten CSDs or venous ischemia provoked via occlusion of two adjacent superficial cortical vein followed by ten induced CSDs (CSD + 2-VO). As an additional control, 15 naïve rats received no intervention except 5-bromo-2′-deoxyuridine (BrdU) treatment for 7 days. Sagittal brain slices (40 μm thick) were co-stained for BrdU and doublecortin (DCX; new immature neuronal cells) on day 9 or NeuN (new mature neuronal cells) on day 28. On day 9 after sham operation, cell proliferation and neurogenesis occurred in the cortex in rats. The sole induction of CSD had no effect. But on days 9 and 28, more proliferating cells and newly formed neurons in the ipsilateral cortex were observed in rats subjected to CSD + 2VO than in rats subjected to sham operation. On days 9 and 28, cell proliferation and neurogenesis in the ipsilateral dentate gyrus was increased in sham-operated rats than in naïve rats. Our data supports the hypothesis that induced cortical neurogenesis after CSD + 2-VO is a direct effect of ischemia, rather than of CSD alone. PMID:28966642

  12. Biphasic direct current shift, haemoglobin desaturation and neurovascular uncoupling in cortical spreading depression

    PubMed Central

    Chang, Joshua C.; Shook, Lydia L.; Biag, Jonathan; Nguyen, Elaine N.; Toga, Arthur W.; Charles, Andrew C.

    2010-01-01

    Cortical spreading depression is a propagating wave of depolarization that plays important roles in migraine, stroke, subarachnoid haemorrhage and brain injury. Cortical spreading depression is associated with profound vascular changes that may be a significant factor in the clinical response to cortical spreading depression events. We used a combination of optical intrinsic signal imaging, electro-physiology, potassium sensitive electrodes and spectroscopy to investigate neurovascular changes associated with cortical spreading depression in the mouse. We identified two distinct phases of altered neurovascular function, one during the propagating cortical spreading depression wave and a second much longer phase after passage of the wave. The direct current shift associated with the cortical spreading depression wave was accompanied by marked arterial constriction and desaturation of cortical haemoglobin. After recovery from the initial cortical spreading depression wave, we observed a second phase of prolonged, negative direct current shift, arterial constriction and haemoglobin desaturation, lasting at least an hour. Persistent disruption of neurovascular coupling was demonstrated by a loss of coherence between electro-physiological activity and perfusion. Extracellular potassium concentration increased during the cortical spreading depression wave, but recovered and remained at baseline after passage of the wave, consistent with different mechanisms underlying the first and second phases of neurovascular dysfunction. These findings indicate that cortical spreading depression is associated with a multiphasic alteration in neurovascular function, including a novel second direct current shift accompanied by arterial constriction and decrease in tissue oxygen supply, that is temporally and mechanistically distinct from the initial propagated cortical spreading depression wave. Vascular/metabolic uncoupling with cortical spreading depression may have important

  13. Cortical spreading depression causes and coincides with tissue hypoxia.

    PubMed

    Takano, Takahiro; Tian, Guo-Feng; Peng, Weiguo; Lou, Nanhong; Lovatt, Ditte; Hansen, Anker J; Kasischke, Karl A; Nedergaard, Maiken

    2007-06-01

    Cortical spreading depression (CSD) is a self-propagating wave of cellular depolarization that has been implicated in migraine and in progressive neuronal injury after stroke and head trauma. Using two-photon microscopic NADH imaging and oxygen sensor microelectrodes in live mouse cortex, we find that CSD is linked to severe hypoxia and marked neuronal swelling that can last up to several minutes. Changes in dendritic structures and loss of spines during CSD are comparable to those during anoxic depolarization. Increasing O2 availability shortens the duration of CSD and improves local redox state. Our results indicate that tissue hypoxia associated with CSD is caused by a transient increase in O2 demand exceeding vascular O2 supply.

  14. In vivo optical imaging of cortical spreading depression in rat

    NASA Astrophysics Data System (ADS)

    Chen, Shangbin; Li, Pengcheng; Luo, Weihua; Gong, Hui; Cheng, Haiying; Luo, Qingming

    2003-12-01

    Intrinsic optical signals imaging (IOSI) and laser speckle imaging (LSI) are both novel techniques for functional neuroimaging in vivo. Combining them to study cortical spreading depression (CSD) which is an important disease model for migraine and other neurological disorders. CSD were induced by pinprick in Sprague-Dawley rats. Intrinsic optical signals (IOS) at 540 nm showed CSD evolution happened in one hemisphere cortex at speeds of 3.7+/-0.4 mm/min, and the vasodilation closely correlated a four-phasic response. By LSI, we observed a transient and significant increase cerebral blood flow (CBF). In this paper, optical imaging would be showed as a powerful tool for describing the hemodynamic character during CSD in rat.

  15. Cortical spreading depression activates and upregulates MMP-9

    PubMed Central

    Gursoy-Ozdemir, Yasemin; Qiu, Jianhua; Matsuoka, Norihiro; Bolay, Hayrunnisa; Bermpohl, Daniela; Jin, Hongwei; Wang, Xiaoying; Rosenberg, Gary A.; Lo, Eng H.; Moskowitz, Michael A.

    2004-01-01

    Cortical spreading depression (CSD) is a propagating wave of neuronal and glial depolarization and has been implicated in disorders of neurovascular regulation such as stroke, head trauma, and migraine. In this study, we found that CSD alters blood-brain barrier (BBB) permeability by activating brain MMPs. Beginning at 3–6 hours, MMP-9 levels increased within cortex ipsilateral to the CSD, reaching a maximum at 24 hours and persisting for at least 48 hours. Gelatinolytic activity was detected earliest within the matrix of cortical blood vessels and later within neurons and pia arachnoid (≥3 hours), particularly within piriform cortex; this activity was suppressed by injection of the metalloprotease inhibitor GM6001 or in vitro by the addition of a zinc chelator (1,10-phenanthroline). At 3–24 hours, immunoreactive laminin, endothelial barrier antigen, and zona occludens-1 diminished in the ipsilateral cortex, suggesting that CSD altered proteins critical to the integrity of the BBB. At 3 hours after CSD, plasma protein leakage and brain edema developed contemporaneously. Albumin leakage was suppressed by the administration of GM6001. Protein leakage was not detected in MMP-9–null mice, implicating the MMP-9 isoform in barrier disruption. We conclude that intense neuronal and glial depolarization initiates a cascade that disrupts the BBB via an MMP-9–dependent mechanism. PMID:15146242

  16. Cortical spreading depolarization increases adult neurogenesis, and alters behavior and hippocampus-dependent memory in mice.

    PubMed

    Urbach, Anja; Baum, Eileen; Braun, Falko; Witte, Otto W

    2017-05-01

    Cortical spreading depolarizations are an epiphenomenon of human brain pathologies and associated with extensive but transient changes in ion homeostasis, metabolism, and blood flow. Previously, we have shown that cortical spreading depolarization have long-lasting consequences on the brains transcriptome and structure. In particular, we found that cortical spreading depolarization stimulate hippocampal cell proliferation resulting in a sustained increase in adult neurogenesis. Since the hippocampus is responsible for explicit memory and adult-born dentate granule neurons contribute to this function, cortical spreading depolarization might influence hippocampus-dependent cognition. To address this question, we induced cortical spreading depolarization in C57Bl/6 J mice by epidural application of 1.5 mol/L KCl and evaluated neurogenesis and behavior at two, four, or six weeks thereafter. Congruent with our previous findings in rats, we found that cortical spreading depolarization increases numbers of newborn dentate granule neurons. Moreover, exploratory behavior and object location memory were consistently enhanced. Reference memory in the water maze was virtually unaffected, whereas memory formation in the Barnes maze was impaired with a delay of two weeks and facilitated after four weeks. These data show that cortical spreading depolarization produces lasting changes in psychomotor behavior and complex, delay- and task-dependent changes in spatial memory, and suggest that cortical spreading depolarization-like events affect the emotional and cognitive outcomes of associated brain pathologies.

  17. Mathematical approaches to modeling of cortical spreading depression

    NASA Astrophysics Data System (ADS)

    Miura, Robert M.; Huang, Huaxiong; Wylie, Jonathan J.

    2013-12-01

    Migraine with aura (MwA) is a debilitating disease that afflicts about 25%-30% of migraine sufferers. During MwA, a visual illusion propagates in the visual field, then disappears, and is followed by a sustained headache. MwA was conjectured by Lashley to be related to some neurological phenomenon. A few years later, Leão observed electrophysiological waves in the brain that are now known as cortical spreading depression (CSD). CSD waves were soon conjectured to be the neurological phenomenon underlying MwA that had been suggested by Lashley. However, the confirmation of the link between MwA and CSD was not made until 2001 by Hadjikhani et al. [Proc. Natl. Acad. Sci. U.S.A. 98, 4687-4692 (2001)] using functional MRI techniques. Despite the fact that CSD has been studied continuously since its discovery in 1944, our detailed understandings of the interactions between the mechanisms underlying CSD waves have remained elusive. The connection between MwA and CSD makes the understanding of CSD even more compelling and urgent. In addition to all of the information gleaned from the many experimental studies on CSD since its discovery, mathematical modeling studies provide a general and in some sense more precise alternative method for exploring a variety of mechanisms, which may be important to develop a comprehensive picture of the diverse mechanisms leading to CSD wave instigation and propagation. Some of the mechanisms that are believed to be important include ion diffusion, membrane ionic currents, osmotic effects, spatial buffering, neurotransmitter substances, gap junctions, metabolic pumps, and synaptic connections. Discrete and continuum models of CSD consist of coupled nonlinear differential equations for the ion concentrations. In this review of the current quantitative understanding of CSD, we focus on these modeling paradigms and various mechanisms that are felt to be important for CSD.

  18. Changes in hemodynamics and light scattering during cortical spreading depression

    NASA Astrophysics Data System (ADS)

    Li, Pengcheng; Yang, Yuanyuan; Luo, Qingming

    2005-01-01

    Cortical spreading depression (CSD) has been known to play an important role in the mechanism of migraine, stroke and brain injure. Optical imaging of intrinsic signals has been shown a powerful method for characterizing the spatial and temporal pattern of the propagation of CSD. However, the possible physiological mechanisms underlying the intrinsic optical signal (IOS) during CSD still remain incompletely understood. In this study, a spectroscopic recording of the change in optical intrinsic signal during CSD was performed and an analysis method based on the modified Beer-Lambert law was used to estimate the changes in the concentration of HbO2 and Hb, and changes in light scattering from the spectra data. The CSD were induced by pinprick in 10 α-chloralose/urethane anesthetized Sprague-Dawley rats. In all experiments, four-phasic changes in optical reflectance were observed at 450 nm ~ 570 nm, and triphasic changes in optical reflectance were observed in the range of 570 nm ~750 nm. But at 750 nm ~ 850 nm, only biphasic changes of optical signal were detected. Converting the spectra data to the changes in light scattering and concentration of Hb and HbO2, we found that the CSD induced an initial increase in concentration of HbO2 (amplitude: 9.0+/-3.7%), which was 26.2+/-18.6 s earlier than the onset of increase of Hb concentration. Furthermore, the concentration of HbO2 showed a four-phasic change, whereas the concentration of Hb only showed a biphasic change. For the changes in light scattering during CSD, a triphasic change was observed.

  19. Simultaneous imaging of intrinsic optical signals and cerebral vessel responses during cortical spreading depression in rats

    NASA Astrophysics Data System (ADS)

    Li, Pengcheng; Chen, Shangbin; Luo, Weihua; Luo, Qingming

    2003-12-01

    Cortical spreading depression (CSD) is an important disease model for migraine and cerebral ischemia. We investigated the spatio-temporal characteristics of the intrinsic optical signals (IOS) at 570 nm and the cerebral blood vessel responses during CSD simultaneously by optical reflectance imaging in vivo. The CSD were induced by pinprick in 10 α-chloralose/urethane anesthetized Sprague-Dawley rats. A four-phasic IOS response was observed at pial arteries and parenchymal sites in all experimental animals and an initial slight pial arteries dilation (21.5%+/-13.6%) and constriction (-4.2%+/-3.5%) precedes the dramatic dilation (69.2%+/-26.1%) of pial arterioles was recorded. Our experimental results show a high correlation (r = 0.89+/-0.025) between the IOS response and the diameter changes of the cerebral blood vessels during CSD in rats.

  20. The effects of anesthetics on cortical spreading depression elicitation and c-fos expression in rats.

    PubMed

    Kitahara, Y; Taga, K; Abe, H; Shimoji, K

    2001-01-01

    The effects of anesthetics on the generation of cortical spreading depression (CSD) were investigated. Volatile anesthetics halothane, isoflurane, sevoflurane (0.5, 1.0, and 2.0 MAC), and the intravenous anesthetic pentobarbital were studied. Cortical spreading depression was induced by 3M-KCl applied to a surface of brain cortex for 30 minutes. Direct current (DC) potential was recorded, and the number, amplitude, and duration of CSDs were observed. With increasing concentrations of each volatile anesthetic, there was a dose-related reduction in CSD frequency but not in CSD amplitude. At 2.0 MAC of sevoflurane the suppression of CSD was less than with the other volatile anesthetics. In addition, the influence of anesthetics on expression of c-fos mRNA was investigated. Additional animals anesthetized by isoflurane or sevoflurane were studied. Five CSDs were elicited by electric stimulation (0.5 mV, 1 second) in each animal. In situ hybridization with 35S-labeled oligonucleotides was used to evaluate the level of c-fos mRNA. The expression of c-fos was observed in the hemisphere in which CSD was elicited, but there was no difference in expression of c-fos among the groups. We conclude that volatile anesthetics can induce suppression of CSD elicitation in a dose dependent manner, but that at high concentrations sevoflurane is significantly less effective than other volatile agents. Pentobarbital has the least effect on KCl-induced CSD. These data suggest that the choice of anesthetics can impact the results of studies examining membrane depolarization and the ionic changes initiated by CSD.

  1. Caffeine/nutrition interaction in the rat brain: Influence on latent inhibition and cortical spreading depression.

    PubMed

    de Aguiar, Márlison José Lima; de Aguiar, Cilene Rejane Ramos Alves; Guedes, Rubem Carlos Araújo

    2011-01-10

    Caffeine, like malnutrition, can produce behavioral and electrophysiological alterations. However, the interaction of both factors remains unclear. Here this interaction has been studied in male Wistar rats previously malnourished during the lactation period by feeding their dams the "regional basic diet" of Northeast Brazil, containing about 8% protein, predominantly from vegetable sources (RBD(8)). At 70-75days of life, a subset of the pups was treated intraperitoneally with 30mg/kg caffeine for 4days while being tested according to the behavioral model of latent inhibition. Another group was subjected to an electrophysiological recording of the phenomenon known as cortical spreading depression, and the effects of caffeine injected during the recording session were evaluated. Caffeine did not affect cortical spreading depression, but antagonized latent inhibition in both the RBD(8)-malnourished rats and in the well-nourished control group fed a chow diet with 22% protein. This effect of caffeine was not seen in malnourished rats fed a protein-supplemented RBD (protein increased to 22% by increasing the proportion of foodstuffs from vegetable origin; RBD(22) group), suggesting that the amino acid imbalance of this diet may modulate the caffeine effects on latent inhibition. The results indicate a differential effect of caffeine in the latent inhibition behavioral model, as compared to the cortical spreading depression phenomenon, and this effect is influenced by the early nutritional status of the animal. We suggest that caffeine may modulate dopaminergic subcortical receptors participating in attention processes, but does not interact at the cortical level, in a way that would affect cortical spreading depression. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. The continuum of spreading depolarizations in acute cortical lesion development: Examining Leão's legacy.

    PubMed

    Hartings, Jed A; Shuttleworth, C William; Kirov, Sergei A; Ayata, Cenk; Hinzman, Jason M; Foreman, Brandon; Andrew, R David; Boutelle, Martyn G; Brennan, K C; Carlson, Andrew P; Dahlem, Markus A; Drenckhahn, Christoph; Dohmen, Christian; Fabricius, Martin; Farkas, Eszter; Feuerstein, Delphine; Graf, Rudolf; Helbok, Raimund; Lauritzen, Martin; Major, Sebastian; Oliveira-Ferreira, Ana I; Richter, Frank; Rosenthal, Eric S; Sakowitz, Oliver W; Sánchez-Porras, Renán; Santos, Edgar; Schöll, Michael; Strong, Anthony J; Urbach, Anja; Westover, M Brandon; Winkler, Maren Kl; Witte, Otto W; Woitzik, Johannes; Dreier, Jens P

    2016-01-01

    A modern understanding of how cerebral cortical lesions develop after acute brain injury is based on Aristides Leão's historic discoveries of spreading depression and asphyxial/anoxic depolarization. Treated as separate entities for decades, we now appreciate that these events define a continuum of spreading mass depolarizations, a concept that is central to understanding their pathologic effects. Within minutes of acute severe ischemia, the onset of persistent depolarization triggers the breakdown of ion homeostasis and development of cytotoxic edema. These persistent changes are diagnosed as diffusion restriction in magnetic resonance imaging and define the ischemic core. In delayed lesion growth, transient spreading depolarizations arise spontaneously in the ischemic penumbra and induce further persistent depolarization and excitotoxic damage, progressively expanding the ischemic core. The causal role of these waves in lesion development has been proven by real-time monitoring of electrophysiology, blood flow, and cytotoxic edema. The spreading depolarization continuum further applies to other models of acute cortical lesions, suggesting that it is a universal principle of cortical lesion development. These pathophysiologic concepts establish a working hypothesis for translation to human disease, where complex patterns of depolarizations are observed in acute brain injury and appear to mediate and signal ongoing secondary damage.

  3. [The Effect of Cortical Spreading Depression Wave on EEG Spectral Power Anaesthesed and Conscious Rats].

    PubMed

    Koroleva, V I; Sakharov, D S; Bogdanov, A V

    2016-01-01

    EEG power changes in anaesthetized and conscious rats were studied (under repeated experiments) in wide frequency band (0.1-200 Hz) during cortical spreading depression wave (SD). In anaesthetized rats the decrease of EEG spectral power was shown through all diapasons under consideration. The most pronounced decay of the EEG power was marked in the 30-40 Hz band (27.3 ± 18.5, p = 2.46 x 10-(11)). In other frequency ranges the power decrease was less but its significance remained high. In conscious rats the simultaneous decay of the EEG power from 20 to 100 Hz range was also the most informative index of SD wave. The maximum power loss was found for band 30-40 Hz (11.2 ± 7.8, p = 2.55 x 10(-7)). It was shown that besides of EEG power decay the development of SD wave was characterized by the appearance of high frequency activity in front of SD and at the end of it. The increase of high-frequency activity in front of SD wave appeared in the ipsilateral hemisphere and moved along the cortex with the velocity of the SD wave itself. However the bursts of high frequency activity at the end of unilateral SD occurred simultaneously in both hemispheres and lasted 1.5-2.5 min. Findings contribute to detection of SD wave on basis of EEG spectral analysis.

  4. Geometry Shapes Propagation: Assessing the Presence and Absence of Cortical Symmetries through a Computational Model of Cortical Spreading Depression.

    PubMed

    Kroos, Julia M; Diez, Ibai; Cortes, Jesus M; Stramaglia, Sebastiano; Gerardo-Giorda, Luca

    2016-01-01

    Cortical spreading depression (CSD), a depolarization wave which originates in the visual cortex and travels toward the frontal lobe, has been suggested to be one neural correlate of aura migraine. To the date, little is known about the mechanisms which can trigger or stop aura migraine. Here, to shed some light on this problem and, under the hypothesis that CSD might mediate aura migraine, we aim to study different aspects favoring or disfavoring the propagation of CSD. In particular, by using a computational neuronal model distributed throughout a realistic cortical mesh, we study the role that the geometry has in shaping CSD. Our results are two-fold: first, we found significant differences in the propagation traveling patterns of CSD, both intra and inter-hemispherically, revealing important asymmetries in the propagation profile. Second, we developed methods able to identify brain regions featuring a peculiar behavior during CSD propagation. Our study reveals dynamical aspects of CSD, which, if applied to subject-specific cortical geometry, might shed some light on how to differentiate between healthy subjects and those suffering migraine.

  5. Geometry Shapes Propagation: Assessing the Presence and Absence of Cortical Symmetries through a Computational Model of Cortical Spreading Depression

    PubMed Central

    Kroos, Julia M.; Diez, Ibai; Cortes, Jesus M.; Stramaglia, Sebastiano; Gerardo-Giorda, Luca

    2016-01-01

    Cortical spreading depression (CSD), a depolarization wave which originates in the visual cortex and travels toward the frontal lobe, has been suggested to be one neural correlate of aura migraine. To the date, little is known about the mechanisms which can trigger or stop aura migraine. Here, to shed some light on this problem and, under the hypothesis that CSD might mediate aura migraine, we aim to study different aspects favoring or disfavoring the propagation of CSD. In particular, by using a computational neuronal model distributed throughout a realistic cortical mesh, we study the role that the geometry has in shaping CSD. Our results are two-fold: first, we found significant differences in the propagation traveling patterns of CSD, both intra and inter-hemispherically, revealing important asymmetries in the propagation profile. Second, we developed methods able to identify brain regions featuring a peculiar behavior during CSD propagation. Our study reveals dynamical aspects of CSD, which, if applied to subject-specific cortical geometry, might shed some light on how to differentiate between healthy subjects and those suffering migraine. PMID:26869913

  6. Diffuse optical correlation tomography of cerebral blood flow during cortical spreading depression in rat brain

    NASA Astrophysics Data System (ADS)

    Zhou, Chao; Yu, Guoqiang; Furuya, Daisuke; Greenberg, Joel; Yodh, Arjun; Durduran, Turgut

    2006-02-01

    Diffuse optical correlation methods were adapted for three-dimensional (3D) tomography of cerebral blood flow (CBF) in small animal models. The image reconstruction was optimized using a noise model for diffuse correlation tomography which enabled better data selection and regularization. The tomographic approach was demonstrated with simulated data and during in-vivo cortical spreading depression (CSD) in rat brain. Three-dimensional images of CBF were obtained through intact skull in tissues(~4mm) deep below the cortex.

  7. Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage.

    PubMed

    Dreier, Jens P; Major, Sebastian; Manning, Andrew; Woitzik, Johannes; Drenckhahn, Chistoph; Steinbrink, Jens; Tolias, Christos; Oliveira-Ferreira, Ana I; Fabricius, Martin; Hartings, Jed A; Vajkoczy, Peter; Lauritzen, Martin; Dirnagl, Ulrich; Bohner, Georg; Strong, Anthony J

    2009-07-01

    The term cortical spreading depolarization (CSD) describes a wave of mass neuronal depolarization associated with net influx of cations and water. Clusters of prolonged CSDs were measured time-locked to progressive ischaemic damage in human cortex. CSD induces tone alterations in resistance vessels, causing either transient hyperperfusion (physiological haemodynamic response) in healthy tissue; or hypoperfusion [inverse haemodynamic response = cortical spreading ischaemia (CSI)] in tissue at risk for progressive damage, which has so far only been shown experimentally. Here, we performed a prospective, multicentre study in 13 patients with aneurysmal subarachnoid haemorrhage, using novel subdural opto-electrode technology for simultaneous laser-Doppler flowmetry (LDF) and direct current-electrocorticography, combined with measurements of tissue partial pressure of oxygen (ptiO(2)). Regional cerebral blood flow and electrocorticography were simultaneously recorded in 417 CSDs. Isolated CSDs occurred in 12 patients and were associated with either physiological, absent or inverse haemodynamic responses. Whereas the physiological haemodynamic response caused tissue hyperoxia, the inverse response led to tissue hypoxia. Clusters of prolonged CSDs were measured in five patients in close proximity to structural brain damage as assessed by neuroimaging. Clusters were associated with CSD-induced spreading hypoperfusions, which were significantly longer in duration (up to 144 min) than those of isolated CSDs. Thus, oxygen depletion caused by the inverse haemodynamic response may contribute to the establishment of clusters of prolonged CSDs and lesion progression. Combined electrocorticography and perfusion monitoring also revealed a characteristic vascular signature that might be used for non-invasive detection of CSD. Low-frequency vascular fluctuations (LF-VF) (f < 0.1 Hz), detectable by functional imaging methods, are determined by the brain's resting neuronal activity

  8. NR2A contributes to genesis and propagation of cortical spreading depression in rats

    PubMed Central

    Bu, Fan; Du, Ruoxing; Li, Yi; Quinn, John P; Wang, Minyan

    2016-01-01

    Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine. Increasing evidence points to an essential role of NR2A-containing NMDA receptors in CSD propagation in vitro; however, whether these receptors mediate CSD genesis in vivo requires clarification and the role of NR2A on CSD propagation is still under debate. Using in vivo CSD in rats with electrophysiology and in vitro CSD in chick retina with intrinsic optical imaging, we addressed the role of NR2A in CSD. We demonstrated that NVP-AAM077, a potent antagonist for NR2A-containing receptors, perfused through microdialysis probes, markedly reduced cortex susceptibility to CSD, but also reduced magnitude of CSD genesis in rats. Additionally, NVP-AAM077 at 0.3 nmol perfused into the contralateral ventricle, considerably suppressed the magnitude of CSD propagation wave and propagation rate in rats. This reduction in CSD propagation was also observed with TCN-201, a negative allosteric modulator selective for NR2A, at 3 μM, in the chick retina. Our data provides strong evidence that NR2A subunit contributes to CSD genesis and propagation, suggesting drugs selectively antagonizing NR2A-containing receptors might constitute a highly specific strategy treating CSD associated migraine with a likely better safety profile. PMID:27001011

  9. Photothrombotic infarction triggers multiple episodes of cortical spreading depression in distant brain regions.

    PubMed

    Dietrich, W D; Feng, Z C; Leistra, H; Watson, B D; Rosenthal, M

    1994-01-01

    The purposes of this study were to determine whether cortical spreading depression occurs outside of the infarct produced by photothrombotic vascular occlusion, and also the direction of spreading. Focal cerebral thrombotic infarction was produced by irradiating the exposed skull of anesthetized rats with green light (560 nm) following systemic injection of rose bengal dye. At proximal sites (approximately 2 mm anterior to the infarct border), transient, severe hyperemic episodes (THEs) lasting 1-2 min were intermittently recorded. THE frequency was greatest in the first hour and declined over a 3-h period. THEs were accompanied (and usually preceded) by a precipitous rise in [K+]0 (from approximately 3 to > 40 mM) and were associated with increases in local tissue oxygen tension (tPO2). Following the rise in [K+]0, clearance of [K+]0 to its pre-THE baseline preceded baseline recovery of CBF. These data indicate that THEs were reactive to physiologic events resembling cortical spreading depression (CSD), which provoked increased demand for oxygen and blood flow, and which spread from proximal sites to areas more distal (approximately 4 mm) from the rim of the evolving infarct. MK-801 (1 mg/kg, i.v.) inhibited subsequent CSD-like episodes. We conclude that photothrombosis-induced ischemia provoked CSD which was triggered either within the infarct core or in the infarct rim and spread to more distal sites. Whether multiple episodes of CSD during infarct generation are responsible for the remote consequences of focal brain injury remains to be determined.

  10. Changes in Mice Brain Spontaneous Electrical Activity during Cortical Spreading Depression due to Mobile Phone Radiation

    PubMed Central

    Sallam, Samera M.; Mohamed, Ehab I.; Dawood, Abdel-Fattah B.

    2008-01-01

    The objective of the present study was to investigate changes in spontaneous EEG activity during cortical spreading depression (CSD) in mice brain. The cortical region of anaesthetized mice were exposed to the electromagnetic fields (EMFs) emitted from a mobile phone (MP, 935.2-960.2 MHz, 41.8 mW/cm2). The effect of EMFs on EEG was investigated before and after exposure to different stimuli (MP, 2% KCl, and MP & 2% KCl). The records of brain spontaneous EEG activity, slow potential changes (SPC), and spindle shaped firings were obtained through an interfaced computer. The results showed increases in the amplitude of evoked spindles by about 87%, 17%, and 226% for MP, 2% KCl, and MP & 2% KCl; respectively, as compared to values for the control group. These results showed that the evoked spindle is a more sensitive indicator of the effect of exposure to EMFs from MP. PMID:23675079

  11. Cortical spreading depression in traumatic brain injuries: is there a role for astrocytes?

    PubMed

    Torrente, Daniel; Cabezas, Ricardo; Avila, Marco Fidel; García-Segura, Luis Miguel; Barreto, George E; Guedes, Rubem Carlos Araújo

    2014-04-17

    Cortical spreading depression (CSD) is a presumably pathophysiological phenomenon that interrupts local cortical function for periods of minutes to hours. This phenomenon is important due to its association with different neurological disorders such as migraine, malignant stroke and traumatic brain injury (TBI). Glial cells, especially astrocytes, play an important role in the regulation of CSD and in the protection of neurons under brain trauma. The correlation of TBI with CSD and the astrocytic function under these conditions remain unclear. This review discusses the possible link of TBI and CSD and its implication for neuronal survival. Additionally, we highlight the importance of astrocytic function for brain protection, and suggest possible therapeutic strategies targeting astrocytes to improve the outcome following TBI-associated CSD.

  12. A multidomain model for ionic electrodiffusion and osmosis with an application to cortical spreading depression

    NASA Astrophysics Data System (ADS)

    Mori, Yoichiro

    2015-07-01

    Ionic electrodiffusion and osmotic water flow are central processes in many physiological systems. We formulate a system of partial differential equations that governs ion movement and water flow in biological tissue. A salient feature of this model is that it satisfies a free energy identity, ensuring the thermodynamic consistency of the model. A numerical scheme is developed for the model in one spatial dimension and is applied to a model of cortical spreading depression, a propagating breakdown of ionic and cell volume homeostasis in the brain.

  13. PSD-95 uncoupling from NMDA receptors by Tat- N-dimer ameliorates neuronal depolarization in cortical spreading depression.

    PubMed

    Kucharz, Krzysztof; Søndergaard Rasmussen, Ida; Bach, Anders; Strømgaard, Kristian; Lauritzen, Martin

    2017-05-01

    Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95 (PSD-95) that binds to nitric oxide synthase (nNOS). Here, we tested whether inhibition of the nNOS/PSD-95/NMDA receptor complex formation by anti-ischemic compound, UCCB01-144 (Tat- N-dimer) ameliorates the persistent effects of cortical spreading depression on cortical function. Using in vivo two-photon microscopy in somatosensory cortex in mice, we show that fluorescently labelled Tat- N-dimer readily crosses blood-brain barrier and accumulates in nerve cells during the first hour after i.v. injection. The Tat- N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO2) responses were preserved. During cortical spreading depression, the Tat- N-dimer reduced the average amplitude of the negative shift in direct current potential by 33% (4.1 mV). Furthermore, the compound diminished the average depression of spontaneous electrocorticographic activity by 11% during first 40 min of post-cortical spreading depression recovery, but did not mitigate the suppressing effect of cortical spreading depression on cortical blood flow and CMRO2. We suggest that uncoupling of PSD-95 from NMDA receptors reduces overall neuronal excitability and the amplitude of the spreading depolarization wave. These findings may be of interest for understanding the neuroprotective effects of the nNOS/PSD-95 uncoupling in stroke.

  14. Cortical High-Density Counterstream Architectures

    PubMed Central

    Markov, Nikola T.; Ercsey-Ravasz, Mária; Van Essen, David C.

    2014-01-01

    Small-world networks provide an appealing description of cortical architecture owing to their capacity for integration and segregation combined with an economy of connectivity. Previous reports of low-density interareal graphs and apparent small-world properties are challenged by data that reveal high-density cortical graphs in which economy of connections is achieved by weight heterogeneity and distance-weight correlations. These properties define a model that predicts many binary and weighted features of the cortical network including a core-periphery, a typical feature of self-organizing information processing systems. Feedback and feedforward pathways between areas exhibit a dual counterstream organization, and their integration into local circuits constrains cortical computation. Here, we propose a bow-tie representation of interareal architecture derived from the hierarchical laminar weights of pathways between the high-efficiency dense core and periphery. PMID:24179228

  15. Cortical high-density counterstream architectures.

    PubMed

    Markov, Nikola T; Ercsey-Ravasz, Mária; Van Essen, David C; Knoblauch, Kenneth; Toroczkai, Zoltán; Kennedy, Henry

    2013-11-01

    Small-world networks provide an appealing description of cortical architecture owing to their capacity for integration and segregation combined with an economy of connectivity. Previous reports of low-density interareal graphs and apparent small-world properties are challenged by data that reveal high-density cortical graphs in which economy of connections is achieved by weight heterogeneity and distance-weight correlations. These properties define a model that predicts many binary and weighted features of the cortical network including a core-periphery, a typical feature of self-organizing information processing systems. Feedback and feedforward pathways between areas exhibit a dual counterstream organization, and their integration into local circuits constrains cortical computation. Here, we propose a bow-tie representation of interareal architecture derived from the hierarchical laminar weights of pathways between the high-efficiency dense core and periphery.

  16. Computational study on cortical spreading depression based on a generalized cellular automaton model

    NASA Astrophysics Data System (ADS)

    Chen, Shangbin; Hu, Lele; Li, Bing; Xu, Changcheng; Liu, Qian

    2009-02-01

    Cortical spreading depression (CSD) is an important neurophysiological phenomenon correlating with some neural disorders, such as migraine, cerebral ischemia and epilepsy. By now, we are still not clear about the mechanisms of CSD's initiation and propagation, also the relevance between CSD and those neural diseases. Nevertheless, characterization of CSD, especially the spatiotemporal evolution, will promote the understanding of the CSD's nature and mechanisms. Besides the previous experimental work on charactering the spatiotemporal evolution of CSD in rats by optical intrinsic signal imaging, a computational study based on a generalized cellular automaton (CA) model was proposed here. In the model, we exploited a generalized neighborhood connection rule: a central CA cell is related with a group of surrounding CA cells with different weight coefficients. By selecting special parameters, the generalized CA model could be transformed to the traditional CA models with von Neumann, Moore and hexagon neighborhood connection means. Hence, the new model covered several properties of CSD simulated in traditional CA models: 1) expanding from the origin site like a circular wave; 2) annihilation of two waves traveling in opposite directions after colliding; 3) wavefront of CSD breaking and recovering when and after encountering an obstacle. By setting different refractory period in the different CA lattice field, different connection coefficient in different direction within the defined neighborhood, inhomogeneous propagation of CSD was simulated with high fidelity. The computational results were analogous to the reported time-varying CSD waves by optical imaging. So, the generalized CA model would be useful to study CSD because of its intuitive appeal and computational efficiency.

  17. Spatio-temporal cerebral blood flow perfusion patterns in cortical spreading depression

    NASA Astrophysics Data System (ADS)

    Verisokin, Andrey Yu.; Verveyko, Darya V.; Postnov, Dmitry E.

    2017-04-01

    Cortical spreading depression (CSD) is an example of one of the most common abnormalities in biophysical brain functioning. Despite the fact that there are many mathematical models describing the cortical spreading depression (CSD), most of them do not take into consideration the role of redistribution of cerebral blood flow (CBF), that results in the formation of spatio-temporal patterns. The paper presents a mathematical model, which successfully explains the CBD role in the CSD process. Numerical study of this model has revealed the formation of stationary dissipative structures, visually analogous to Turing structures. However, the mechanism of their formation is not diffusion. We show these structures occur due to another type of spatial coupling, that is related to tissue perfusion rate. The proposed model predicts that at similar state of neurons the distribution of blood flow and oxygenation may by different. Currently, this effect is not taken into account when the Blood oxygen-level dependent (BOLD) contrast imaging used in functional magnetic resonance imaging (fMRI). Thus, the diagnosis on the BOLD signal can be ambiguous. We believe that our results can be used in the future for a more correct interpretation of the data obtained with fMRI, NIRS and other similar methods for research of the brain activity.

  18. Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5

    PubMed Central

    Viggiano, Emanuela; Monda, Vincenzo; Messina, Antonietta; Moscatelli, Fiorenzo; Valenzano, Anna; Tafuri, Domenico; Cibelli, Giuseppe; De Luca, Bruno; Messina, Giovanni; Monda, Marcellino

    2016-01-01

    Depression of electrocorticogram propagating over the cortex surface results in cortical spreading depression (CSD), which is probably related to the pathophysiology of stroke, epilepsy, and migraine. However, preconditioning with CSD produces neuroprotection to subsequent ischemic episodes. Such effects require the expression or activation of several genes, including neuroprotective ones. Recently, it has been demonstrated that the expression of the uncoupling proteins (UCPs) 2 and 5 is amplified during brain ischemia and their expression exerts a long-term effect upon neuron protection. To evaluate the neuroprotective consequence of CSD, the expression of UCP-5 in the brain cortex was measured following CSD induction. CSD was evoked in four samples of rats, which were sacrificed after 2 hours, 4 hours, 6 hours, and 24 hours. Western blot analyses were carried out to measure UCP-5 concentrations in the prefrontal cortices of both hemispheres, and immunohistochemistry was performed to determine the localization of UCP-5 in the brain cortex. The results showed a significant elevation in UCP-5 expression at 24 hours in all cortical strata. Moreover, UCP-5 was triggered by CSD, indicating that UCP-5 production can have a neuroprotective effect. PMID:27468234

  19. Spreading Photoparoxysmal EEG Response is Associated with an Abnormal Cortical Excitability Pattern

    ERIC Educational Resources Information Center

    Siniatchkin, Michael; Groppa, Sergey; Jerosch, Bettina; Muhle, Hiltrud; Kurth, Christoph; Shepherd, Alex J.; Siebner, Hartwig; Stephani, Ulrich

    2007-01-01

    Photosensitivity or photoparoxysmal response (PPR) is a highly heritable electroencephalographic trait characterized by an abnormal cortical response to intermittent photic stimulation (IPS). In PPR-positive individuals, IPS induces spikes, spike-waves or intermittent slow waves. The PPR may be restricted to posterior visual areas (i.e. local PPR…

  20. Spreading Photoparoxysmal EEG Response is Associated with an Abnormal Cortical Excitability Pattern

    ERIC Educational Resources Information Center

    Siniatchkin, Michael; Groppa, Sergey; Jerosch, Bettina; Muhle, Hiltrud; Kurth, Christoph; Shepherd, Alex J.; Siebner, Hartwig; Stephani, Ulrich

    2007-01-01

    Photosensitivity or photoparoxysmal response (PPR) is a highly heritable electroencephalographic trait characterized by an abnormal cortical response to intermittent photic stimulation (IPS). In PPR-positive individuals, IPS induces spikes, spike-waves or intermittent slow waves. The PPR may be restricted to posterior visual areas (i.e. local PPR…

  1. Poloxamer-188 and citicoline provide neuronal membrane integrity and protect membrane stability in cortical spreading depression.

    PubMed

    Yıldırım, Timur; Eylen, Alpaslan; Lule, Sevda; Erdener, Sefik Evren; Vural, Atay; Karatas, Hulya; Ozveren, Mehmet Faik; Dalkara, Turgay; Gursoy-Ozdemir, Yasemin

    2015-01-01

    Under pathological conditions such as brain trauma, subarachnoid hemorrhage and stroke, cortical spreading depression (CSD) or peri-infarct depolarizations contribute to brain damage in animal models of neurological disorders as well as in human neurological diseases. CSD causes transient megachannel opening on the neuronal membrane, which may compromise neuronal survival under pathological conditions. Poloxamer-188 (P-188) and citicoline are neuroprotectants with membrane sealing properties. The aim of this study is to investigate the effect of P-188 and citicoline on the neuronal megachannel opening induced by CSD in the mouse brain. We have monitored megachannel opening with propidium iodide, a membrane impermeable fluorescent dye and, demonstrate that P-188 and citicoline strikingly decreased CSD-induced neuronal PI influx in cortex and hippocampal dentate gyrus. Therefore, these agents may be providing neuroprotection by blocking megachannel opening, which may be related to their membrane sealing action and warrant further investigation for treatment of traumatic brain injury and ischemic stroke.

  2. Critical role of calcitonin gene-related peptide receptors in cortical spreading depression

    PubMed Central

    Tozzi, Alessandro; de Iure, Antonio; Di Filippo, Massimiliano; Costa, Cinzia; Caproni, Stefano; Pisani, Antonio; Bonsi, Paola; Picconi, Barbara; Cupini, Letizia M.; Materazzi, Serena; Geppetti, Pierangelo; Sarchielli, Paola; Calabresi, Paolo

    2012-01-01

    Cortical spreading depression (CSD) is a key pathogenetic step in migraine with aura. Dysfunctions of voltage-dependent and receptor-operated channels have been implicated in the generation of CSD and in the pathophysiology of migraine. Although a known correlation exists between migraine and release of the calcitonin gene-related peptide (CGRP), the possibility that CGRP is involved in CSD has not been examined in detail. We analyzed the pharmacological mechanisms underlying CSD and investigated the possibility that endogenous CGRP contributes to this phenomenon. CSD was analyzed in rat neocortical slices by imaging of the intrinsic optical signal. CSD was measured as the percentage of the maximal surface of a cortical slice covered by the propagation of intrinsic optical signal changes during an induction episode. Reproducible CSD episodes were induced through repetitive elevations of extracellular potassium concentration. AMPA glutamate receptor antagonism did not inhibit CSD, whereas NMDA receptor antagonism did inhibit CSD. Blockade of voltage-dependent sodium channels by TTX also reduced CSD. CSD was also decreased by the antiepileptic drug topiramate, but not by carbamazepine. Interestingly, endogenous CGRP was released in the cortical tissue in a calcium-dependent manner during CSD, and three different CGRP receptor antagonists had a dose-dependent inhibitory effect on CSD, suggesting a critical role of CGRP in this phenomenon. Our findings show that both glutamate NMDA receptors and voltage-dependent sodium channels play roles in CSD. They also demonstrate that CGRP antagonism reduces CSD, supporting the possible use of drugs targeting central CGRP receptors as antimigraine agents. PMID:23112192

  3. Cortical Spreading Depression Causes Unique Dysregulation of Inflammatory Pathways in a Transgenic Mouse Model of Migraine.

    PubMed

    Eising, Else; Shyti, Reinald; 't Hoen, Peter A C; Vijfhuizen, Lisanne S; Huisman, Sjoerd M H; Broos, Ludo A M; Mahfouz, Ahmed; Reinders, Marcel J T; Ferrari, Michel D; Tolner, Else A; de Vries, Boukje; van den Maagdenberg, Arn M J M

    2017-05-01

    Familial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of migraine with aura caused by mutations in CACNA1A that encodes the α1A subunit of voltage-gated CaV2.1 calcium channels. Transgenic knock-in mice that carry the human FHM1 R192Q missense mutation ('FHM1 R192Q mice') exhibit an increased susceptibility to cortical spreading depression (CSD), the mechanism underlying migraine aura. Here, we analysed gene expression profiles from isolated cortical tissue of FHM1 R192Q mice 24 h after experimentally induced CSD in order to identify molecular pathways affected by CSD. Gene expression profiles were generated using deep serial analysis of gene expression sequencing. Our data reveal a signature of inflammatory signalling upon CSD in the cortex of both mutant and wild-type mice. However, only in the brains of FHM1 R192Q mice specific genes are up-regulated in response to CSD that are implicated in interferon-related inflammatory signalling. Our findings show that CSD modulates inflammatory processes in both wild-type and mutant brains, but that an additional unique inflammatory signature becomes expressed after CSD in a relevant mouse model of migraine.

  4. Cortical Spreading Depression Elicited in Rat Brain after Exposure to Microwave from GSM Mobile Phone

    PubMed Central

    Sallam, Samera M.

    2006-01-01

    The aim of the present work is to evaluate possibility of microwave emitted by cellular phone that can elicit cortical spreading depression (CSD) in rat brain and studying the characteristics of the evoked signals. (CSD) was elicited in cerebral cortex of anesthetized rats after exposure to microwave irradiation (935.2-960.2 MHz) from Global System for Mobile communications (GSM) mobile phone. With the microwave output of about 8.5 mW at the antenna - tissue surface (4mm in diameter), CSD was elicited after 50 sec irradiation from the beginning of a received signal to the mobile and after 35 sec irradiation from the beginning of a transmitted signal from the mobile. CSD was elicited in about 90% of experiments after irradiation by both types of signal exposure. The results have shown that slow potential change (SPC) has an amplitude of 4.5 ± 0.75 mV, duration of 1.5 ± 0.5 min and propagated speed of 3 mm/min on the average. The amplitude, duration and behaviour of SPC of the evoked spreading depression were found to be affected by irradiation time and the method of exposure. PMID:23674979

  5. Effects of sciatic nerve stimulation on the propagation of cortical spreading depression

    NASA Astrophysics Data System (ADS)

    Sun, Xiaoli; Yu, Zhidong; Zeng, Shaoqun; Luo, Qingming; Li, Pengcheng

    2008-02-01

    Cortical spreading depression (CSD) is an important pathological model of migraine and is related to other neural disorders, such as cerebral ischemia and epilepsy. It has been reported that brain stimulation is a quite effective way to treat neural diseases. However, direct stimulation could cause harm to brain. If peripheral nerve stimulation could have the same treatment, it would be essential to investigate the mechanisms of peripheral nerve and the study of sciatic nerve stimulation would have profound clinical meaning. In this paper, we used optical intrinsic signal imaging (OISI) and extracellular electrophysiologic recording techniques to study the effects of sciatic nerve stimulation on the propagation of CSD. We found that: (1) continuous sciatic nerve stimulation on rats caused a decrease in light intensity on the whole cortex, which meant an increase in cerebral blood volume(CBV); (2) the spreading velocity of CSD declined from 3.63+/- 0.272 mm/min to 3.06+/-0.260 mm/min during sciatic nerve stimulation, compared with that without sciatic nerve stimulation. In summary, data suggests that sciatic nerve stimulation elicits a response of cortex and causes a slowdown in the propagation of CSD.

  6. [Cortical spreading depolarization phenomena in patients with traumatic and ischemic brain injuries. Results of a pilot study].

    PubMed

    Sueiras, M; Sahuquillo, J; García-López, B; Sánchez-Guerrero, Á; Poca, M A; Santamarina, E; Riveiro, M; Fabricius, M; Strong, A J

    2014-10-01

    To determine the frequency and duration of cortical spreading depolarization (CSD) and CSD-like episodes in patients with traumatic brain injury (TBI) and malignant middle cerebral artery infarction (MMCAI) requiring craniotomy. A descriptive observational study was carried out during 19 months. Neurocritical patients. Sixteen patients were included: 9 with MMCAI and 7 with moderate or severe TBI, requiring surgical treatment. A 6-electrode subdural electrocorticographic (ECoG) strip was placed onto the perilesional cortex. An analysis was made of the time profile and the number and duration of CSD and CSD-like episodes recorded from the ECoGs. Of the 16 patients enrolled, 9 presented episodes of CSD or CSD-like phenomena, of highly variable frequency and duration. Episodes of CSD and CSD-like phenomena are frequently detected in the ischemic penumbra and/or traumatic cortical regions of patients with MMCAI who require decompressive craniectomy or of patients with contusional TBI. Copyright © 2013 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  7. Physical exercise versus fluoxetine: antagonistic effects on cortical spreading depression in Wistar rats.

    PubMed

    Mirelle Costa Monteiro, Heloísa; Lima Barreto-Silva, Nathália; Elizabete Dos Santos, Gracyelle; de Santana Santos, Amanda; Séfora Bezerra Sousa, Mariana; Amâncio-Dos-Santos, Ângela

    2015-09-05

    The antidepressant fluoxetine and physical exercise exert similar effects on the serotoninergic system by increasing brain serotonin availability, and both show antagonistic action on cortical excitability. Here we provide the first assessment of the interaction of the two together on cortical spreading depression (CSD) in young adult rats. Wistar rats (40-60 days of life) received fluoxetine (10mg/kg/d, orogastrically) or an equivalent volume of water. Half of the animals from each condition were assigned to perform physical exercise in a treadmill, and the other half formed the sedentary (non-treadmill) control groups. Body parameters (Lee index and thoracic and abdominal circumferences) and the velocity of CSD propagation were investigated. Fluoxetine+exercise animals had less weight gain (78.68±3.19g) than either the fluoxetine-only (93.34±4.77g) or exercise-only group (97.04±3.48g), but body parameters did not differ among them. The velocity of CSD propagation was reduced in the fluoxetine-only and exercise-only groups compared to sedentary water controls (3.24±0.39mm/min). For the fluoxetine+exercise group, CSD velocity values were significantly lower (2.92±0.22mm/min) than for fluoxetine only (3.03±0.35mm/min); however, they were similar to values for the exercise-only group (2.96±0.23mm/min). These findings confirm the similar effects of fluoxetine and exercise and suggest a greater effect of physical exercise in reducing brain excitability.

  8. A mathematical model of the metabolic and perfusion effects on cortical spreading depression.

    PubMed

    Chang, Joshua C; Brennan, Kevin C; He, Dongdong; Huang, Huaxiong; Miura, Robert M; Wilson, Phillip L; Wylie, Jonathan J

    2013-01-01

    Cortical spreading depression (CSD) is a slow-moving ionic and metabolic disturbance that propagates in cortical brain tissue. In addition to massive cellular depolarizations, CSD also involves significant changes in perfusion and metabolism-aspects of CSD that had not been modeled and are important to traumatic brain injury, subarachnoid hemorrhage, stroke, and migraine. In this study, we develop a mathematical model for CSD where we focus on modeling the features essential to understanding the implications of neurovascular coupling during CSD. In our model, the sodium-potassium-ATPase, mainly responsible for ionic homeostasis and active during CSD, operates at a rate that is dependent on the supply of oxygen. The supply of oxygen is determined by modeling blood flow through a lumped vascular tree with an effective local vessel radius that is controlled by the extracellular potassium concentration. We show that during CSD, the metabolic demands of the cortex exceed the physiological limits placed on oxygen delivery, regardless of vascular constriction or dilation. However, vasoconstriction and vasodilation play important roles in the propagation of CSD and its recovery. Our model replicates the qualitative and quantitative behavior of CSD--vasoconstriction, oxygen depletion, extracellular potassium elevation, prolonged depolarization--found in experimental studies. We predict faster, longer duration CSD in vivo than in vitro due to the contribution of the vasculature. Our results also help explain some of the variability of CSD between species and even within the same animal. These results have clinical and translational implications, as they allow for more precise in vitro, in vivo, and in silico exploration of a phenomenon broadly relevant to neurological disease.

  9. Effects of experimental traumatic brain injury and impaired glutamate transport on cortical spreading depression.

    PubMed

    Hosseini-Zare, Mahshid Sadat; Gu, Feng; Abdulla, Ahmad; Powell, Simon; Žiburkus, Jokūbas

    2017-09-01

    Cortical spreading depression (CSD) is associated with traumatic brain injury (TBI), stroke, migraines, and seizures. Typically, following TBIs and other insults, neuronal excitability in and around the area of the injury is affected, with reported increases in local glutamate signaling. Astrocytic glutamate transporters are critical for precise regulation of the extracellular glutamate availability. However, it remains unclear how impaired astrocytic glutamate transport or an acute TBI affect characteristics of the CSD. We quantified the properties of CSD using whole-cell and extracellular electrophysiological recordings, and voltage-sensitive dye imaging (VSDI) in rat visual cortex in vitro. To model impaired astrocytic glutamate transport, we used astrocytic glutamate transporter blocker (2S, 3S)-3-[3-[4-(trifluoromethyl) benzoylamino] benzyloxy] aspartate (TFB-TBOA). In addition, an acute incision through the superficial cortical layers was used to model the effects of acute traumatic brain injury (TBI) on CSD characteristics. Both manipulations; impaired glutamate cycling and acute cut profoundly affected the physiological properties of cell firing, latency to CSD formation, and its frequency of occurrence. VSD imaging analysis revealed significant changes in spatiotemporal dynamics and propagation of the CSD, suggesting that the cut itself may not initiate CSD depolarizing waves, but rather attract them. Blockade of GLT-1 caused significant reduction in whole-cell sodium currents and changes in CSD wave spatiotemporal characteristics as well, slowing it or even 'trapping' its propagation. Our results reveal new information about CSD properties in these pathological conditions and demonstrate an important role of GLT-1 in regulation of CSD. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. A Mathematical Model of the Metabolic and Perfusion Effects on Cortical Spreading Depression

    PubMed Central

    Chang, Joshua C.; Brennan, Kevin C.; He, Dongdong; Huang, Huaxiong; Miura, Robert M.; Wilson, Phillip L.; Wylie, Jonathan J.

    2013-01-01

    Cortical spreading depression (CSD) is a slow-moving ionic and metabolic disturbance that propagates in cortical brain tissue. In addition to massive cellular depolarizations, CSD also involves significant changes in perfusion and metabolism—aspects of CSD that had not been modeled and are important to traumatic brain injury, subarachnoid hemorrhage, stroke, and migraine. In this study, we develop a mathematical model for CSD where we focus on modeling the features essential to understanding the implications of neurovascular coupling during CSD. In our model, the sodium-potassium–ATPase, mainly responsible for ionic homeostasis and active during CSD, operates at a rate that is dependent on the supply of oxygen. The supply of oxygen is determined by modeling blood flow through a lumped vascular tree with an effective local vessel radius that is controlled by the extracellular potassium concentration. We show that during CSD, the metabolic demands of the cortex exceed the physiological limits placed on oxygen delivery, regardless of vascular constriction or dilation. However, vasoconstriction and vasodilation play important roles in the propagation of CSD and its recovery. Our model replicates the qualitative and quantitative behavior of CSD—vasoconstriction, oxygen depletion, extracellular potassium elevation, prolonged depolarization—found in experimental studies. We predict faster, longer duration CSD in vivo than in vitro due to the contribution of the vasculature. Our results also help explain some of the variability of CSD between species and even within the same animal. These results have clinical and translational implications, as they allow for more precise in vitro, in vivo, and in silico exploration of a phenomenon broadly relevant to neurological disease. PMID:23967075

  11. Does single cortical spreading depression elicit pain behaviour in freely moving rats?

    PubMed

    Akcali, Didem; Sayin, Aslihan; Sara, Yildirim; Bolay, Hayrunnisa

    2010-10-01

    Behavioural animal studies are critical, particularly to translate results to human beings. Cortical spreading depression (CSD) has been implicated in migraine pathogenesis. We aimed to investigate the effects of CSD on the behaviour of freely moving rats, since available CSD models do not include awake animals. We developed a new model to induce single CSD by applying topical N-methyl-D-aspartate (NMDA) and employed a combination of an automated behavioural analysis system, video camera and ultrasonic vocalisation (USV) calls for the first time. Electrocorticograms were also studied during CSD in freely moving rats. Behaviour associated with cephalic pain was assessed in a group of rats that received sumatriptan. Cortical c-fos immunoreactivity was performed in order to confirm CSD. NMDA induced single CSD in ipsilateral cortex, evoked freezing behaviour (P < 0.01) and increased the number of wet dog shakes (WDS; P < 0.01). Grooming, locomotion, eating, drinking, and circling were not significantly altered among groups. Ultrasonic vocalisations compatible with pain calls (22-27 kHz) were only detected in 3 out of 25 rats. Sumatriptan did not significantly reduce the freezing behaviour. CSD induced significant c-fos expression in ipsilateral cerebral cortex and amygdala (P < 0.01). CSD induces freezing behaviour by invoking anxiety/fear via amygdala activation in freely-moving rats. Single CSD is unlikely to lead to severe pain in freely-moving rats, though the development of mild or vague pain cannot be excluded. The relevance of rat behavioural responses triggered by CSD to migraine symptoms in humans needs further evaluation.

  12. Left frontal cortical activation and spreading of alternatives: tests of the action-based model of dissonance.

    PubMed

    Harmon-Jones, Eddie; Harmon-Jones, Cindy; Fearn, Meghan; Sigelman, Jonathan D; Johnson, Peter

    2008-01-01

    The action-based model of dissonance predicts that following decisional commitment, approach-oriented motivational processes occur to assist in translating the decision into effective and unconflicted behavior. Therefore, the modulation of these approach-oriented processes should affect the degree to which individuals change their attitudes to be more consistent with the decisional commitment (spreading of alternatives). Experiment 1 demonstrated that a neurofeedback-induced decrease in relative left frontal cortical activation, which has been implicated in approach motivational processes, caused a reduction in spreading of alternatives. Experiment 2 manipulated an action-oriented mindset following a decision and demonstrated that the action-oriented mindset caused increased activation in the left frontal cortical region as well as increased spreading of alternatives. Discussion focuses on how this integration of neuroscience and dissonance theory benefits both parent literatures. Copyright 2008 APA, all rights reserved.

  13. Elicitation interval dependent spatiotemporal evolution of cortical spreading depression waves revealed by optical intrinsic signal imaging

    NASA Astrophysics Data System (ADS)

    Chen, Shangbin; Gong, Hui; Zeng, Shaoqun; Luo, Qingming; Li, Pengcheng

    2007-02-01

    This study aimed to investigate the variation of propagation patterns of successive cortical spreading depression (CSD) waves induced by K + or pinprick in rat cortex. In the K + induction group, 18 Sprague-Dawley rats under Î+/--chloralose/urethane anesthesia were used to elicit CSD by 1 M KCl solution in the frontal cortex. Optical intrinsic signal imaging (OISI) at an isosbestic point of hemoglobin (550 nm) was applied to examine regional cerebral blood volume (CBV) changes in the parieto-occipital cortex. In 6 of the 18 rats, OISI was performed in conjunction with DC potential recording of the cortex. The results of this group were reported previously. In the pinprick group, 6 rats were used to induce CSD by pinprick with 8 min interval, and the other 6 rats were pricked with 4 min. CBV changes during CSD appeared as repetitive propagation of wave-like hyperemia at a speed of 3.7+/-0.4 mm/min, which was characterized by a significant negative peak (-14.3+/-3.2%) in the reflectance signal. Except for the first CSD wave, the following waves don't spread fully in the observed cortex all the time and they might abort in the medial area. Independent on the stimulation of pinprick or K+, a short interval of the current CSD to the last CSD no more than 4 min would induce the current CSD be partially propagated. For the first time, the data reveals the time-varying propagation patterns of CSD waves might be affected by the interval between CSD waves. The results suggest that the propagation patterns of a series of CSD waves are time-varying in different regions of rat cortex, and the variation is related to the interval between CSD waves.

  14. Aquaporin-4 Regulates the Velocity and Frequency of Cortical Spreading Depression in Mice

    PubMed Central

    Yao, Xiaoming; Smith, Alex J.; Jin, Byung-Ju; Zador, Zsolt; Manley, Geoffrey T.; Verkman, A.S.

    2016-01-01

    The astrocyte water channel aquaporin-4 (AQP4) regulates extracellular space (ECS) K+ concentration ([K+]e) and volume dynamics following neuronal activation. Here, we investigated how AQP4-mediated changes in [K+]e and ECS volume affect the velocity, frequency and amplitude of cortical spreading depression (CSD) depolarizations produced by surface KCl application in wild-type (AQP4+/+) and AQP4-deficient (AQP4−/−) mice. Contrary to initial expectations, both the velocity and frequency of CSD were significantly reduced in AQP4−/− mice when compared to AQP4+/+ mice, by 22% and 32%, respectively. Measurement of [K+]e with K+-selective microelectrodes demonstrated an increase to ~35 mM during spreading depolarizations in both AQP4+/+ and AQP4−/− mice, but the rates of [K+]e increase (3.5 vs. 1.5 mM/s) and reuptake (t1/2 33 vs. 61 s) were significantly reduced in AQP4−/− mice. ECS volume fraction measured by trimethylammonium iontophoresis was greatly reduced during depolarizations from 0.18 to 0.053 in AQP4+/+ mice, and 0.23 to 0.063 in AQP4−/− mice. Analysis of the experimental data using a mathematical model of CSD propagation suggested that the reduced velocity of CSD depolarizations in AQP4−/− mice was primarily a consequence of the slowed increase in [K+]e during neuronal depolarization. These results demonstrate that AQP4 effects on [K+]e and ECS volume dynamics accelerate CSD propagation. PMID:25944186

  15. In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures.

    PubMed

    Cain, Stuart M; Bohnet, Barry; LeDue, Jeffrey; Yung, Andrew C; Garcia, Esperanza; Tyson, John R; Alles, Sascha R A; Han, Huili; van den Maagdenberg, Arn M J M; Kozlowski, Piotr; MacVicar, Brian A; Snutch, Terrance P

    2017-02-28

    Migraine is characterized by severe headaches that can be preceded by an aura likely caused by cortical spreading depression (SD). The antiepileptic pregabalin (Lyrica) shows clinical promise for migraine therapy, although its efficacy and mechanism of action are unclear. As detected by diffusion-weighted MRI (DW-MRI) in wild-type (WT) mice, the acute systemic administration of pregabalin increased the threshold for SD initiation in vivo. In familial hemiplegic migraine type 1 mutant mice expressing human mutations (R192Q and S218L) in the CaV2.1 (P/Q-type) calcium channel subunit, pregabalin slowed the speed of SD propagation in vivo. Acute systemic administration of pregabalin in vivo also selectively prevented the migration of SD into subcortical striatal and hippocampal regions in the R192Q strain that exhibits a milder phenotype and gain of CaV2.1 channel function. At the cellular level, pregabalin inhibited glutamatergic synaptic transmission differentially in WT, R192Q, and S218L mice. The study describes a DW-MRI analysis method for tracking the progression of SD and provides support and a mechanism of action for pregabalin as a possible effective therapy in the treatment of migraine.

  16. Computational model of cerebral blood flow redistribution during cortical spreading depression

    NASA Astrophysics Data System (ADS)

    Verisokin, Andrey Y.; Verveyko, Darya V.; Postnov, Dmitry E.

    2016-04-01

    In recent decades modelling studies on cortical spreading depression (CSD) and migraine waves successfully contributed to formation of modern view on these fundamental phenomena of brain physiology. However, due to the extreme complexity of object under study (brain cortex) and the diversity of involved physiological pathways, the development of new mathematical models of CSD is still a very relevant and challenging research problem. In our study we follow the functional modelling approach aimed to map the action of known physiological pathways to the specific nonlinear mechanisms that govern formation and evolution of CSD wave patterns. Specifically, we address the role of cerebral blood flow (CBF) redistribution that is caused by excessive neuronal activity by means of neurovascular coupling and mediates a spatial pattern of oxygen and glucose delivery. This in turn changes the local metabolic status of neural tissue. To build the model we simplify the web of known cell-to-cell interactions within a neurovascular unit by selecting the most relevant ones, such as local neuron-induced elevation of extracellular potassium concentration and biphasic response of arteriole radius. We propose the lumped description of distance-dependent hemodynamic coupling that fits the most recent experimental findings.

  17. Effects of the nitric oxide donor, DEA/NO on cortical spreading depression.

    PubMed

    Wang, M; Obrenovitch, T P; Urenjak, J

    2003-06-01

    Cortical spreading depression (CSD) is a transient disruption of local ionic homeostasis that may promote migraine attacks and the progression of stroke lesions. We reported previously that the local inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME) delayed markedly the initiation of the recovery of ionic homeostasis from CSD. Here we describe a novel method for selective, controlled generation of exogenous NO in a functioning brain region. It is based on microdialysis perfusion of the NO donor, 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA/NO). As DEA/NO does not generate NO at alkaline pH, and as the brain has a strong acid-base buffering capacity, DEA/NO was perfused in a medium adjusted at alkaline (but unbuffered) pH. Without DEA/NO, such a microdialysis perfusion medium did not alter CSD. DEA/NO (1, 10 and 100 microM) had little effect on CSD by itself, but it reversed in a concentration-dependent manner the effects of NOS inhibition by 1 mM L-NAME. These data demonstrate that increased formation of endogenous NO associated with CSD is critical for subsequent, rapid recovery of cellular ionic homeostasis. In this case, the molecular targets for NO may be located either on brain cells to suppress mechanisms directly involved in CSD genesis, or on local blood vessels to couple flow to the increased energy demand associated with CSD.

  18. In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures

    PubMed Central

    Cain, Stuart M.; Bohnet, Barry; LeDue, Jeffrey; Yung, Andrew C.; Garcia, Esperanza; Tyson, John R.; Alles, Sascha R. A.; Han, Huili; van den Maagdenberg, Arn M. J. M.; Kozlowski, Piotr; MacVicar, Brian A.; Snutch, Terrance P.

    2017-01-01

    Migraine is characterized by severe headaches that can be preceded by an aura likely caused by cortical spreading depression (SD). The antiepileptic pregabalin (Lyrica) shows clinical promise for migraine therapy, although its efficacy and mechanism of action are unclear. As detected by diffusion-weighted MRI (DW-MRI) in wild-type (WT) mice, the acute systemic administration of pregabalin increased the threshold for SD initiation in vivo. In familial hemiplegic migraine type 1 mutant mice expressing human mutations (R192Q and S218L) in the CaV2.1 (P/Q-type) calcium channel subunit, pregabalin slowed the speed of SD propagation in vivo. Acute systemic administration of pregabalin in vivo also selectively prevented the migration of SD into subcortical striatal and hippocampal regions in the R192Q strain that exhibits a milder phenotype and gain of CaV2.1 channel function. At the cellular level, pregabalin inhibited glutamatergic synaptic transmission differentially in WT, R192Q, and S218L mice. The study describes a DW-MRI analysis method for tracking the progression of SD and provides support and a mechanism of action for pregabalin as a possible effective therapy in the treatment of migraine. PMID:28223480

  19. Minimum conditions for the induction of cortical spreading depression in brain slices

    PubMed Central

    Tang, Yujie T.; Mendez, Jorge M.; Theriot, Jeremy J.; Sawant, Punam M.; López-Valdés, Héctor E.; Ju, Y. Sungtaek

    2014-01-01

    Cortical spreading depression (CSD) occurs during various forms of brain injury such as stroke, subarachnoid hemorrhage, and brain trauma, but it is also thought to be the mechanism of the migraine aura. It is therefore expected to occur over a range of conditions including the awake behaving state. Yet it is unclear how such a massive depolarization could occur under relatively benign conditions. Using a microfluidic device with focal stimulation capability in a mouse brain slice model, we varied extracellular potassium concentration as well as the area exposed to increased extracellular potassium to determine the minimum conditions necessary to elicit CSD. Importantly, we focused on potassium levels that are physiologically plausible (≤145 mM; the intracellular potassium concentration). We found a strong correlation between the threshold concentration and the slice area exposed to increased extracellular potassium: minimum area of exposure was needed with the highest potassium concentration, while larger areas were needed at lower concentrations. We also found that moderate elevations of extracellular potassium were able to elicit CSD in relatively small estimated tissue volumes that might be activated under noninjury conditions. Our results thus show that CSD may be inducible under the conditions that expected in migraine aura as well as those related to brain trauma. PMID:25122714

  20. Involvement of NMDA receptor subtypes in cortical spreading depression in rats assessed by fMRI.

    PubMed

    Shatillo, Artem; Salo, Raimo A; Giniatullin, Rashid; Gröhn, Olli H

    2015-06-01

    Cortical spreading depression (CSD) is a phenomenon implicated in migraine with aura and associated with other neurological disorders (e.g. stroke, brain trauma). Current evidence points to the essential role of NMDA receptors in CSD mechanisms. However, the roles of multiple subunits of NMDA receptors expressed in neurons, glia and blood vessels in vivo, are little explored. Using BOLD fMRI of urethane anesthetized rats as an integrative CSD readout, we tested the involvement of different NMDA receptor subtypes in CSD induction and propagation. Rats were treated with a non-selective NMDA blocker (MK-801), NR2B antagonist (ifenprodil) or a NR2A selective antagonist (TCN-201). CSD was induced during fMRI scanning by application of KCl onto the cerebral cortex and fMRI data were collected by 9.4 T MRI. The non-specific NMDA antagonist MK-801 completely blocked CSD, which was not observed in the NR2A group where TCN-201 did not alter the CSD features. Unexpectedly, the NR2B specific antagonist ifenprodil largely promoted the initial negative phase of the BOLD CSD response, likely due to altered neurovascular coupling. Our data suggest key roles and differential involvement of NMDA receptor subtypes in CSD generation and propagation, highlighting an important role for the NR2B subtype. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Direct, live imaging of cortical spreading depression and anoxic depolarisation using a fluorescent, voltage-sensitive dye

    PubMed Central

    Farkas, Eszter; Pratt, Rosalind; Sengpiel, Frank; Obrenovitch, Tihomir P

    2008-01-01

    Perilesion depolarisations, whether transient anoxic depolarisation (AD) or spreading depression (SD), occur in stroke models and in patients with acute brain ischaemia, but their contribution to lesion progression remains unclear. As these phenomena correspond to waves of cellular depolarisation, we have developed a technique for their live imaging with a fluorescent voltage-sensitive (VS) dye (RH-1838). Method development and validation were performed in two different preparations: chicken retina, to avoid any vascular interference; and cranial window exposing the cortical surface of anaesthetised rats. Spreading depression was produced by high-K medium, and AD by complete terminal ischaemia in rats. After dye loading, the preparation was illuminated at its excitation wavelength and fluorescence changes were recorded sequentially with a charge-coupled device camera. No light was recorded when the VS dye was omitted, ruling out the contribution of any endogenous fluorophore. With both preparations, the changes in VS dye fluorescence with SD were analogous to those of the DC (direct current) potential recorded with glass electrodes. Although some blood quenching of the emitted light was identified, the VS dye signatures of SD had a good signal-to-noise ratio and were reproducible. The changes in VS dye fluorescence associated with AD were more complex because of additional interferents, especially transient brain swelling with subsequent shrinkage. However, the kinetics of the AD-associated changes in VS dye fluorescence was also analogous to that of the DC potential. In conclusion, this method provides the imaging equivalent of electrical extracellular DC potential recording, with the SD and AD negative shifts translating directly to fluorescence increase. PMID:17971792

  2. Direct, live imaging of cortical spreading depression and anoxic depolarisation using a fluorescent, voltage-sensitive dye.

    PubMed

    Farkas, Eszter; Pratt, Rosalind; Sengpiel, Frank; Obrenovitch, Tihomir P

    2008-02-01

    Perilesion depolarisations, whether transient anoxic depolarisation (AD) or spreading depression (SD), occur in stroke models and in patients with acute brain ischaemia, but their contribution to lesion progression remains unclear. As these phenomena correspond to waves of cellular depolarisation, we have developed a technique for their live imaging with a fluorescent voltage-sensitive (VS) dye (RH-1838). Method development and validation were performed in two different preparations: chicken retina, to avoid any vascular interference; and cranial window exposing the cortical surface of anaesthetised rats. Spreading depression was produced by high-K medium, and AD by complete terminal ischaemia in rats. After dye loading, the preparation was illuminated at its excitation wavelength and fluorescence changes were recorded sequentially with a charge-coupled device camera. No light was recorded when the VS dye was omitted, ruling out the contribution of any endogenous fluorophore. With both preparations, the changes in VS dye fluorescence with SD were analogous to those of the DC (direct current) potential recorded with glass electrodes. Although some blood quenching of the emitted light was identified, the VS dye signatures of SD had a good signal-to-noise ratio and were reproducible. The changes in VS dye fluorescence associated with AD were more complex because of additional interferents, especially transient brain swelling with subsequent shrinkage. However, the kinetics of the AD-associated changes in VS dye fluorescence was also analogous to that of the DC potential. In conclusion, this method provides the imaging equivalent of electrical extracellular DC potential recording, with the SD and AD negative shifts translating directly to fluorescence increase.

  3. Ignition's glow: Ultra-fast spread of global cortical activity accompanying local "ignitions" in visual cortex during conscious visual perception.

    PubMed

    Noy, N; Bickel, S; Zion-Golumbic, E; Harel, M; Golan, T; Davidesco, I; Schevon, C A; McKhann, G M; Goodman, R R; Schroeder, C E; Mehta, A D; Malach, R

    2015-09-01

    Despite extensive research, the spatiotemporal span of neuronal activations associated with the emergence of a conscious percept is still debated. The debate can be formulated in the context of local vs. global models, emphasizing local activity in visual cortex vs. a global fronto-parietal "workspace" as the key mechanisms of conscious visual perception. These alternative models lead to differential predictions with regard to the precise magnitude, timing and anatomical spread of neuronal activity during conscious perception. Here we aimed to test a specific aspect of these predictions in which local and global models appear to differ - namely the extent to which fronto-parietal regions modulate their activity during task performance under similar perceptual states. So far the main experimental results relevant to this debate have been obtained from non-invasive methods and led to conflicting interpretations. Here we examined these alternative predictions through large-scale intracranial measurements (Electrocorticogram - ECoG) in 43 patients and 4445 recording sites. Both ERP and broadband high frequency (50-150 Hz - BHF) responses were examined through the entire cortex during a simple 1-back visual recognition memory task. Our results reveal short latency intense visual responses, localized first in early visual cortex followed (at ∼200 ms) by higher order visual areas, but failed to show significant delayed (300 ms) visual activations. By contrast, oddball image repeat events, linked to overt motor responses, were associated with a significant increase in a delayed (300 ms) peak of BHF power in fronto-parietal cortex. Comparing BHF responses with ERP revealed an additional peak in the ERP response - having a similar latency to the well-studied P3 scalp EEG response. Posterior and temporal regions demonstrated robust visual category selectivity. An unexpected observation was that high-order visual cortex responses were essentially concurrent (at ∼200 ms

  4. Altered hypermetabolic response to cortical spreading depolarizations after traumatic brain injury in rats.

    PubMed

    Balança, Baptiste; Meiller, Anne; Bezin, Laurent; Dreier, Jens P; Marinesco, Stéphane; Lieutaud, Thomas

    2017-05-01

    Spreading depolarizations are waves of near-complete breakdown of neuronal transmembrane ion gradients, free energy starving, and mass depolarization. Spreading depolarizations in electrically inactive tissue are associated with poor outcome in patients with traumatic brain injury. Here, we studied changes in regional cerebral blood flow and brain oxygen (PbtO2), glucose ([Glc]b), and lactate ([Lac]b) concentrations in rats, using minimally invasive real-time sensors. Rats underwent either spreading depolarizations chemically triggered by KCl in naïve cortex in absence of traumatic brain injury or spontaneous spreading depolarizations in the traumatic penumbra after traumatic brain injury, or a cluster of spreading depolarizations triggered chemically by KCl in a remote window from which spreading depolarizations invaded penumbral tissue. Spreading depolarizations in noninjured cortex induced a hypermetabolic response characterized by a decline in [Glc]b and monophasic increases in regional cerebral blood flow, PbtO2, and [Lac]b, indicating transient hyperglycolysis. Following traumatic brain injury, spontaneous spreading depolarizations occurred, causing further decline in [Glc]b and reducing the increase in regional cerebral blood flow and biphasic responses of PbtO2 and [Lac]b, followed by prolonged decline. Recovery of PbtO2 and [Lac]b was significantly delayed in traumatized animals. Prespreading depolarization [Glc]b levels determined the metabolic response to clusters. The results suggest a compromised hypermetabolic response to spreading depolarizations and slower return to physiological conditions following traumatic brain injury-induced spreading depolarizations.

  5. Early vibrissae removal facilitates cortical spreading depression propagation in the brain of well-nourished and malnourished developing rats.

    PubMed

    da Silva Tenório, Angélica; de Oliveira, Ilka Daniela Vitor Alves; Guedes, Rubem Carlos Araújo

    2009-08-01

    Reduced sensory input activity during brain development can induce morphological and physiological changes in the cerebral cortex, altering their response properties. Malnutrition delays the formation of somatosensory pathways. Here we used cortical spreading depression as a neurophysiological parameter to investigate electrophysiological changes after vibrissae removal in well-nourished and malnourished rats. Male Wistar rat pups had the right mystacial vibrissae-removed at postnatal days 2-3, and were submitted to spreading depression recording at 30-40 days of life. In both nutritional conditions, spreading depression velocities were increased in the hemisphere contralateral to the vibrissae removal, as compared to age- and nutrition-matched non-lesioned controls, in which no inter-hemispheric differences were found. In contrast to the well-nourished rats, in the vibrissae-removed malnourished animals the spreading depression propagation in the ipsilateral hemisphere decreased as compared to the corresponding hemisphere of the non-lesioned malnourished rats. It is concluded that deprivation of sensory input from whiskers during brain development facilitates spreading depression propagation, and early malnutrition seems to influence this effect. Since the effect persisted until 40 days, it is tempting to suggest that it is permanent, or at least long-lasting. Data might contribute to the understanding of sensory input deprivation-induced plasticity mechanisms underlying cerebral electrophysiological changes in the developing brain.

  6. δ-Opioid receptor agonists inhibit migraine-related hyperalgesia, aversive state and cortical spreading depression in mice

    PubMed Central

    Pradhan, Amynah A; Smith, Monique L; Zyuzin, Jekaterina; Charles, Andrew

    2014-01-01

    Background and Purpose Migraine is an extraordinarily common brain disorder for which treatment options continue to be limited. Agonists that activate the δ-opioid receptor may be promising for the treatment of migraine as they are highly effective for the treatment of chronic rather than acute pain, do not induce hyperalgesia, have low abuse potential and have anxiolytic and antidepressant properties. The aim of this study was to investigate the therapeutic potential of δ-opioid receptor agonists for migraine by characterizing their effects in mouse migraine models. Experimental Approach Mechanical hypersensitivity was assessed in mice treated with acute and chronic doses of nitroglycerin (NTG), a known human migraine trigger. Conditioned place aversion to NTG was also measured as a model of migraine-associated negative affect. In addition, we assessed evoked cortical spreading depression (CSD), an established model of migraine aura, in a thinned skull preparation. Key Results NTG evoked acute and chronic mechanical and thermal hyperalgesia in mice, as well as conditioned place aversion. Three different δ-opioid receptor agonists, SNC80, ARM390 and JNJ20788560, significantly reduced NTG-evoked hyperalgesia. SNC80 also abolished NTG-induced conditioned place aversion, suggesting that δ-opioid receptor activation may also alleviate the negative emotional state associated with migraine. We also found that SNC80 significantly attenuated CSD, a model that is considered predictive of migraine preventive therapies. Conclusions and Implications These data show that δ-opioid receptor agonists modulate multiple basic mechanisms associated with migraine, indicating that δ-opioid receptors are a promising therapeutic target for this disorder. PMID:24467301

  7. Mathematical Imaging and Modeling of Cortical Spreading Depression and Wound Healing

    DTIC Science & Technology

    2015-02-05

    Spreading Depression and W mmd Healing Sb. GRANT NUMBER Sc. PROGRAM ELEMENT NUMBER 611102 6. AUTHORS Sd. PROJECT NUMBER Tom Chou Se. TASK NUMBER...ACRONYM(S) (ES) ARO U.S. Anny Research Office 11 . SPONSOR/MONITOR’S REPORT P.O. Box 12211 NUMBER(S) Research Triangle Park, NC 27709-2211 58386-MA...Spreading Depression and Wound Healing." The research conducted under this grant represents advances made in image analysis, front tracking, modeling

  8. Viral protein targeting to the cortical endoplasmic reticulum is required for cell-cell spreading in plants.

    PubMed

    Wu, Chih-Hang; Lee, Shu-Chuan; Wang, Chao-Wen

    2011-05-02

    Many plant RNA viruses use their nonstructural proteins to target and move through the cortical endoplasmic reticulum (ER) tubules within the plant intercellular junction for cell-to-cell spreading. Most of these proteins, including the triple-gene-block 3 protein (TGBp3) of Potexvirus, are ER membrane proteins. We previously showed that TGBp3 of the Bamboo mosaic potexvirus partitions into tubular subdomains of the ER in both yeast and plants, but the mechanism and physiological significance of this localization is unclear. Here, we demonstrate that a sorting signal present in TGBp3 is necessary and sufficient for its oligomerization and for targeting integral membrane proteins into puncta within curved ER tubules. Mutations in the TGBp3 sorting signal impair viral spread, and plants infected with viruses harboring these mutants were either asymptomatic or had reduced symptoms. Thus, we propose that Potexvirus use the sorting signal in TGBp3 to target infectious viral derivatives to cortical ER tubules for transmission through the intercellular junctions in plants.

  9. High-Degree Neurons Feed Cortical Computations.

    PubMed

    Timme, Nicholas M; Ito, Shinya; Myroshnychenko, Maxym; Nigam, Sunny; Shimono, Masanori; Yeh, Fang-Chin; Hottowy, Pawel; Litke, Alan M; Beggs, John M

    2016-05-01

    Recent work has shown that functional connectivity among cortical neurons is highly varied, with a small percentage of neurons having many more connections than others. Also, recent theoretical developments now make it possible to quantify how neurons modify information from the connections they receive. Therefore, it is now possible to investigate how information modification, or computation, depends on the number of connections a neuron receives (in-degree) or sends out (out-degree). To do this, we recorded the simultaneous spiking activity of hundreds of neurons in cortico-hippocampal slice cultures using a high-density 512-electrode array. This preparation and recording method combination produced large numbers of neurons recorded at temporal and spatial resolutions that are not currently available in any in vivo recording system. We utilized transfer entropy (a well-established method for detecting linear and nonlinear interactions in time series) and the partial information decomposition (a powerful, recently developed tool for dissecting multivariate information processing into distinct parts) to quantify computation between neurons where information flows converged. We found that computations did not occur equally in all neurons throughout the networks. Surprisingly, neurons that computed large amounts of information tended to receive connections from high out-degree neurons. However, the in-degree of a neuron was not related to the amount of information it computed. To gain insight into these findings, we developed a simple feedforward network model. We found that a degree-modified Hebbian wiring rule best reproduced the pattern of computation and degree correlation results seen in the real data. Interestingly, this rule also maximized signal propagation in the presence of network-wide correlations, suggesting a mechanism by which cortex could deal with common random background input. These are the first results to show that the extent to which a neuron

  10. High-Degree Neurons Feed Cortical Computations

    PubMed Central

    Timme, Nicholas M.; Ito, Shinya; Shimono, Masanori; Yeh, Fang-Chin; Litke, Alan M.; Beggs, John M.

    2016-01-01

    Recent work has shown that functional connectivity among cortical neurons is highly varied, with a small percentage of neurons having many more connections than others. Also, recent theoretical developments now make it possible to quantify how neurons modify information from the connections they receive. Therefore, it is now possible to investigate how information modification, or computation, depends on the number of connections a neuron receives (in-degree) or sends out (out-degree). To do this, we recorded the simultaneous spiking activity of hundreds of neurons in cortico-hippocampal slice cultures using a high-density 512-electrode array. This preparation and recording method combination produced large numbers of neurons recorded at temporal and spatial resolutions that are not currently available in any in vivo recording system. We utilized transfer entropy (a well-established method for detecting linear and nonlinear interactions in time series) and the partial information decomposition (a powerful, recently developed tool for dissecting multivariate information processing into distinct parts) to quantify computation between neurons where information flows converged. We found that computations did not occur equally in all neurons throughout the networks. Surprisingly, neurons that computed large amounts of information tended to receive connections from high out-degree neurons. However, the in-degree of a neuron was not related to the amount of information it computed. To gain insight into these findings, we developed a simple feedforward network model. We found that a degree-modified Hebbian wiring rule best reproduced the pattern of computation and degree correlation results seen in the real data. Interestingly, this rule also maximized signal propagation in the presence of network-wide correlations, suggesting a mechanism by which cortex could deal with common random background input. These are the first results to show that the extent to which a neuron

  11. Three-dimensional visualization with large data sets: a simulation of spreading cortical depression in human brain.

    PubMed

    Ertürk, Korhan Levent; Şengül, Gökhan

    2012-01-01

    We developed 3D simulation software of human organs/tissues; we developed a database to store the related data, a data management system to manage the created data, and a metadata system for the management of data. This approach provides two benefits: first of all the developed system does not require to keep the patient's/subject's medical images on the system, providing less memory usage. Besides the system also provides 3D simulation and modification options, which will help clinicians to use necessary tools for visualization and modification operations. The developed system is tested in a case study, in which a 3D human brain model is created and simulated from 2D MRI images of a human brain, and we extended the 3D model to include the spreading cortical depression (SCD) wave front, which is an electrical phoneme that is believed to cause the migraine.

  12. Association of seizures with cortical spreading depression and peri-infarct depolarisations in the acutely injured human brain

    PubMed Central

    Fabricius, Martin; Fuhr, Susanne; Willumsen, Lisette; Dreier, Jens P; Bhatia, Robin; Boutelle, Martyn G.; Hartings, Jed A; Bullock, Ross; Strong, Anthony J; Lauritzen, Martin

    2008-01-01

    Objective To test the co-occurrence and interrelation of ictal activity and cortical spreading depressions (CSDs) - including the related periinfarct depolarisations in acute brain injury caused by trauma, and spontaneous subarachnoid and/or intracerebral haemorrhage. Methods 63 patients underwent craniotomy and electrocorticographic (ECoG) recordings were taken near foci of damaged cortical tissue for up to 10 days. Results 32 of 63 patients exhibited CSDs (5 to 75 episodes), and 11 had ECoGraphic seizure activity (1-81 episodes). Occurrence of seizures was significantly associated with CSD, as 10 of 11 patients with seizures also had CSD (p=0.007, 2-tailed Fishers exact test). Clinically overt seizures were only observed in one patient. Each patient with CSD and seizures displayed one of four different patterns of interaction between CSD and seizures. In four patients CSD was immediately preceded by prolonged seizure activity. In three patients the two phenomena were separated in time: multiple CSDs were replaced by ictal activity. In one patient seizures appeared to trigger repeated CSDs at the adjacent electrode. In two patients ongoing repeated seizures were interrupted each time CSD occurred. Conclusions Seizure activity occurs in association with CSD in the injured human brain. Significance ECoG recordings in brain injury patients provide insight into pathophysiological mechanisms that is not accessible by scalp EEG recordings. PMID:18621582

  13. Hyperperfusion counteracted by transient rapid vasoconstriction followed by long-lasting oligemia induced by cortical spreading depression in anesthetized mice

    PubMed Central

    Unekawa, Miyuki; Tomita, Yutaka; Toriumi, Haruki; Osada, Takashi; Masamoto, Kazuto; Kawaguchi, Hiroshi; Itoh, Yoshiaki; Kanno, Iwao; Suzuki, Norihiro

    2015-01-01

    Cortical spreading depression (CSD) involves mass depolarization of neurons and glial cells accompanied with changes in regional cerebral blood flow (rCBF) and energy metabolism. To further understand the mechanisms of CBF response, we examined the temporal diametric changes in pial arteries, pial veins, and cortical capillaries. In urethane-anesthetized mice, the diameters of these vessels were measured while simultaneously recording rCBF with a laser Doppler flowmeter. We observed a considerable increase in rCBF during depolarization in CSD induced by application of KCl, accompanied by a transient dip of rCBF with marked vasoconstriction of pial arteries, which resembled the response to pin-prick-induced CSD. Arterial constriction diminished or disappeared during the second and third passages of CSD, whereas the rCBF increase was maintained without a transient dip. Long-lasting oligemia with a decrease in the reciprocal of mean transit time of injected dye and mild constriction of pial arteries was observed after several passages of the CSD wave. These results indicate that CSD-induced rCBF changes consist of initial hyperemia with a transient dip and followed by a long-lasting oligemia, partially corresponding to the diametric changes of pial arteries, and further suggest that vessels other than pial arteries, such as intracortical vessels, are involved. PMID:25586145

  14. Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer's pathology

    PubMed Central

    Schmitz, Taylor W.; Nathan Spreng, R.; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Khachaturian, Zaven; Sorensen, Greg; Kuller, Lew; Raichle, Marc; Paul, Steven; Davies, Peter; Fillit, Howard; Hefti, Franz; Holtzman, Davie; Mesulam, M Marcel; Potter, William; Snyder, Peter; Schwartz, Adam; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor-Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Thal, Leon; Buckholtz, Neil; Albert, Marylyn; Frank, Richard; Hsiao, John; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; de Toledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; D'Agostino, Daniel; Kielb, Stephanie; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Wong, Terence Z.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H. S.; Lu, Po H.; Bartzokis, George; Graff-Radford, Neill R.; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Farlow, Martin R.; Hake, AnnMarie; Matthews, Brandy R.; Herring, Scott; Hunt, Cynthia; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging-Yuek; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristine; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Hudson, Leon; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T.-Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Santulli, Robert B.; Kitzmiller, Tamar J.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Finger, Elizabether; Pasternak, Stephen; Rachinsky, Irina; Drost, Dick; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Smith, Karen Elizabeth; Relkin, Norman; Chaing, Gloria; Raudin, Lisa; Smith, Amanda; Fargher, Kristin; Raj, Balebail Ashok; Neylan, Thomas; Grafman, Jordan; Davis, Melissa; Morrison, Rosemary; Hayes, Jacqueline; Finley, Shannon; Friedl, Karl; Fleischman, Debra; Arfanakis, Konstantinos; James, Olga; Massoglia, Dino; Fruehling, J. Jay; Harding, Sandra; Peskind, Elaine R.; Petrie, Eric C.; Li, Gail; Yesavage, Jerome A.; Taylor, Joy L.; Furst, Ansgar J.

    2016-01-01

    There is considerable debate whether Alzheimer's disease (AD) originates in basal forebrain or entorhinal cortex. Here we examined whether longitudinal decreases in basal forebrain and entorhinal cortex grey matter volume were interdependent and sequential. In a large cohort of age-matched older adults ranging from cognitively normal to AD, we demonstrate that basal forebrain volume predicts longitudinal entorhinal degeneration. Models of parallel degeneration or entorhinal origin received negligible support. We then integrated volumetric measures with an amyloid biomarker sensitive to pre-symptomatic AD pathology. Comparison between cognitively matched normal adult subgroups, delineated according to the amyloid biomarker, revealed abnormal degeneration in basal forebrain, but not entorhinal cortex. Abnormal degeneration in both basal forebrain and entorhinal cortex was only observed among prodromal (mildly amnestic) individuals. We provide evidence that basal forebrain pathology precedes and predicts both entorhinal pathology and memory impairment, challenging the widely held belief that AD has a cortical origin. PMID:27811848

  15. Resistance to High-Stakes Testing Spreads

    ERIC Educational Resources Information Center

    Schaeffer, Bob

    2012-01-01

    A rising tide of protest is sweeping across the nation as growing numbers of parents, teachers, administrators and academics take action against high-stakes testing. Instead of test-and-punish policies, which have failed to improve academic performance or equity, the movement is pressing for broader forms of assessment. From Texas to New York and…

  16. Resistance to High-Stakes Testing Spreads

    ERIC Educational Resources Information Center

    Schaeffer, Bob

    2012-01-01

    A rising tide of protest is sweeping across the nation as growing numbers of parents, teachers, administrators and academics take action against high-stakes testing. Instead of test-and-punish policies, which have failed to improve academic performance or equity, the movement is pressing for broader forms of assessment. From Texas to New York and…

  17. Prooxidant versus antioxidant brain action of ascorbic acid in well-nourished and malnourished rats as a function of dose: a cortical spreading depression and malondialdehyde analysis.

    PubMed

    Mendes-da-Silva, Rosângela Figueiredo; Lopes-de-Morais, Andréia Albuquerque Cunha; Bandim-da-Silva, Maria Eduarda; Cavalcanti, Gabriela de Araujo; Rodrigues, Ana Rafaela Oliveira; Andrade-da-Costa, Belmira Lara da Silveira; Guedes, Rubem Carlos Araújo

    2014-11-01

    Although ascorbic acid (AA) is an antioxidant, under certain conditions it can facilitate oxidation, which may underlie the opposite actions of AA on brain excitability in distinct seizure models. Here, we investigated whether chronic AA administration during brain development alters cortical excitability as a function of AA dose, as indexed by cortical spreading depression (CSD) and by the levels of lipid peroxidation-induced malondialdehyde. Well-nourished and early-malnourished rats received per gavage 30, 60, or 120 mg/kg/d of AA, saline, or no gavage treatment (naïve group) at postnatal days 7-28. CSD propagation and malondialdehyde levels were analyzed at 30-40 days. Confirming previous observations, CSD velocities were significantly higher in the early-malnourished groups than in the well-nourished groups. AA dose was important: 30 mg/kg/d AA decelerated CSD and reduced malondialdehyde levels, whereas 60 mg/kg/d and 120 mg/kg/d accelerated CSD and augmented malondialdehyde levels compared with the corresponding saline and naïve groups. Our findings reinforce previous suggestion that AA acts as an antioxidant in the brain when administered at low doses, but as a prooxidant at high doses, as indicated by CSD propagation and malondialdehyde levels.

  18. Cortical Surface Reconstruction from High-Resolution MR Brain Images

    PubMed Central

    Osechinskiy, Sergey; Kruggel, Frithjof

    2012-01-01

    Reconstruction of the cerebral cortex from magnetic resonance (MR) images is an important step in quantitative analysis of the human brain structure, for example, in sulcal morphometry and in studies of cortical thickness. Existing cortical reconstruction approaches are typically optimized for standard resolution (~1 mm) data and are not directly applicable to higher resolution images. A new PDE-based method is presented for the automated cortical reconstruction that is computationally efficient and scales well with grid resolution, and thus is particularly suitable for high-resolution MR images with submillimeter voxel size. The method uses a mathematical model of a field in an inhomogeneous dielectric. This field mapping, similarly to a Laplacian mapping, has nice laminar properties in the cortical layer, and helps to identify the unresolved boundaries between cortical banks in narrow sulci. The pial cortical surface is reconstructed by advection along the field gradient as a geometric deformable model constrained by topology-preserving level set approach. The method's performance is illustrated on exvivo images with 0.25–0.35 mm isotropic voxels. The method is further evaluated by cross-comparison with results of the FreeSurfer software on standard resolution data sets from the OASIS database featuring pairs of repeated scans for 20 healthy young subjects. PMID:22481909

  19. N-Palmitoylethanolamine Prevents the Run-down of Amplitudes in Cortical Spreading Depression Possibly Implicating Proinflammatory Cytokine Release

    PubMed Central

    Richter, Frank; Koulen, Peter; Kaja, Simon

    2016-01-01

    Cortical spreading depression (CSD), a wave of neuronal depolarization in the cerebral cortex following traumatic brain injury or cerebral ischemia, significantly aggravates brain damage. Here, we tested whether N-palmitoylethanolamine (PEA), a substance that effectively reduces lesion volumes and neurological deficits after ischemic stroke, influences CSD. CSD was elicited chemically in adult rats and occurrence, amplitude, duration and propagation velocity of CSD was determined prior to and for 6 hours after intraperitoneal injection of PEA. The chosen systemic administration of PEA stabilized the amplitude of CSD for at least four hours and prevented the run-down of amplitudes that is typically observed and was also seen in untreated controls. The propagation velocity of the CSD waves was unaltered indicating stable neuronal excitability. The stabilization of CSD amplitudes by PEA indicates that inhibition or prevention of CSD does not underlie PEA’s profound neuroprotective effect. Rather, PEA likely inhibits proinflammatory cytokine release thereby preventing the run-down of CSD amplitudes. This contribution of PEA to the maintenance of neuronal excitability in healthy tissue during CSD potentially adds to neuroprotection outside a damaged area, while other mechanisms control PEA-mediated neuroprotection in damaged tissue resulting from traumatic brain injury or cerebral ischemia. PMID:27004851

  20. Large-Scale Mass Spectrometry Imaging Investigation of Consequences of Cortical Spreading Depression in a Transgenic Mouse Model of Migraine

    NASA Astrophysics Data System (ADS)

    Carreira, Ricardo J.; Shyti, Reinald; Balluff, Benjamin; Abdelmoula, Walid M.; van Heiningen, Sandra H.; van Zeijl, Rene J.; Dijkstra, Jouke; Ferrari, Michel D.; Tolner, Else A.; McDonnell, Liam A.; van den Maagdenberg, Arn M. J. M.

    2015-06-01

    Cortical spreading depression (CSD) is the electrophysiological correlate of migraine aura. Transgenic mice carrying the R192Q missense mutation in the Cacna1a gene, which in patients causes familial hemiplegic migraine type 1 (FHM1), exhibit increased propensity to CSD. Herein, mass spectrometry imaging (MSI) was applied for the first time to an animal cohort of transgenic and wild type mice to study the biomolecular changes following CSD in the brain. Ninety-six coronal brain sections from 32 mice were analyzed by MALDI-MSI. All MSI datasets were registered to the Allen Brain Atlas reference atlas of the mouse brain so that the molecular signatures of distinct brain regions could be compared. A number of metabolites and peptides showed substantial changes in the brain associated with CSD. Among those, different mass spectral features showed significant ( t-test, P < 0.05) changes in the cortex, 146 and 377 Da, and in the thalamus, 1820 and 1834 Da, of the CSD-affected hemisphere of FHM1 R192Q mice. Our findings reveal CSD- and genotype-specific molecular changes in the brain of FHM1 transgenic mice that may further our understanding about the role of CSD in migraine pathophysiology. The results also demonstrate the utility of aligning MSI datasets to a common reference atlas for large-scale MSI investigations.

  1. Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury.

    PubMed

    Lauritzen, Martin; Dreier, Jens Peter; Fabricius, Martin; Hartings, Jed A; Graf, Rudolf; Strong, Anthony John

    2011-01-01

    Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves.

  2. Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury

    PubMed Central

    Lauritzen, Martin; Dreier, Jens Peter; Fabricius, Martin; Hartings, Jed A; Graf, Rudolf; Strong, Anthony John

    2011-01-01

    Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves. PMID:21045864

  3. Nitroglycerin enhances the propagation of cortical spreading depression: comparative studies with sumatriptan and novel kynurenic acid analogues

    PubMed Central

    Knapp, Levente; Szita, Bence; Kocsis, Kitti; Vécsei, László; Toldi, József

    2017-01-01

    Background The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified. Materials and methods In vivo electrophysiological experiments were performed to investigate the effect of nitroglycerin (NTG) on CSD induced by KCl application. In addition, sumatriptan and newly synthesized neuroactive substances (analogues of the neuromodulator kynurenic acid [KYNA]) were also tested. Results The basic parameters of CSDs were unchanged following NTG administration; however, propagation failure was decreased compared to the controls. Sumatriptan decreased the number of CSDs, whereas propagation failure was as minimal as in the NTG group. On the other hand, both of the KYNA analogues restored the ratio of propagation to the control level. Discussion The ratio of propagation appeared to be the indicator of the effect of NTG. This is the first study providing direct evidence that NTG influences CSD; furthermore, we observed different effects of sumatriptan and KYNA analogues. Sumatriptan changed the generation of CSDs, whereas the analogues acted on the propagation of the waves. Our experimental design overlaps with a large spectrum of processes present in migraine pathophysiology, and it can be a useful experimental model for drug screening. PMID:28053504

  4. Unexpected effects of peripherally administered kynurenic acid on cortical spreading depression and related blood–brain barrier permeability

    PubMed Central

    Oláh, Gáspár; Herédi, Judit; Menyhárt, Ákos; Czinege, Zsolt; Nagy, Dávid; Fuzik, János; Kocsis, Kitti; Knapp, Levente; Krucsó, Erika; Gellért, Levente; Kis, Zsolt; Farkas, Tamás; Fülöp, Ferenc; Párdutz, Árpád; Tajti, János; Vécsei, László; Toldi, József

    2013-01-01

    Cortical spreading depression (CSD) involves a slowly-propagating depolarization wave in the cortex, which can appear in numerous pathophysiological conditions, such as migraine with aura, stroke, and traumatic brain injury. Neurons and glial cells are also depolarized transiently during the phenomena. CSD is followed by a massive increase in glutamate release and by changes in the brain microcirculation. The aim of this study was to investigate the effects of two N-methyl-D-aspartate receptor antagonists, endogenous kynurenic acid (KYNA) and dizocilpine, on CSD and the related blood–brain barrier (BBB) permeability in rats. In intact animals, KYNA hardly crosses the BBB but has some positive features as compared with its precursor L-Kynurenine, which is frequently used in animal studies (KYNA cannot be metabolized to excitotoxic agents such as 3-hydroxy-L-kynurenine and quinolinic acid). We therefore investigated the possible effects of peripherally administered KYNA. Repetitive CSD waves were elicited by the application of 1 M KCl solution to the cortex. Direct current-electrocorticograms were measured for 1 hour. Four parameters of the waves were compared. Evans blue dye and fluorescent microscopy were used to study the possible changes in the permeability of the BBB. The results demonstrated that N-methyl-D-aspartate receptor antagonists can reduce the number of CSD waves and decrease the permeability of the BBB during CSD. These results suggest that KYNA itself or its derivatives may offer a new approach in the therapy of migraines. PMID:24068867

  5. Early malnutrition, but not age, modulates in the rat the L-Arginine facilitating effect on cortical spreading depression.

    PubMed

    Frazão, Marília Ferreira; Silva de Seixas Maia, Luciana Maria; Guedes, Rubem Carlos Araújo

    2008-12-05

    Nutritional factors acting during brain development can permanently alter brain electrophysiology. L-Arginine is the precursor of nitric oxide synthesis, which can modulate brain function. Here we investigated the effect of early-in-life administration (during postnatal days 7-28) of L-Arginine (300 mg/(kg day)) on cortical spreading depression (CSD), recorded in well-nourished and malnourished (large litters technique) rats aged 30-40 days (young) and 90-110 days (adult). Compared to water-treated controls, well-nourished L-Arginine-treated rats, but not the malnourished ones, displayed higher CSD velocities (P<0.05) at both ages. The mean+/-S.D. CSD velocities (in mm/min) were: for water- and L-Arginine well-nourished rats, 3.78+/-0.23 and 4.36+/-0.19 (young groups), and 3.28+/-0.16 and 4.09+/-0.30 (adult); for the same conditions in the malnourished rats, 4.22+/-0.09 and 4.27+/-0.21 (young), and 4.11+/-0.18 and 4.21+/-0.33 (adult). L-Arginine treatment did not affect body and brain weights. It is concluded that early L-Arginine treatment long lastingly increased brain CSD-susceptibility and this effect is abolished by early malnutrition.

  6. Transcriptomic Changes in Rat Cortex and Brainstem After Cortical Spreading Depression With or Without Pretreatment With Migraine Prophylactic Drugs.

    PubMed

    Sintas, Cèlia; Fernàndez-Castillo, Noèlia; Vila-Pueyo, Marta; Pozo-Rosich, Patricia; Macaya, Alfons; Cormand, Bru

    2017-04-01

    Migraine with aura is a subtype of migraine characterized by transient neurological disturbances that usually precede headache. Cortical spreading depression (CSD) is the likely pathophysiological correlate of the aura phase of migraine, found in common and rare forms of migraine, such as familial hemiplegic migraine. CSD is a depolarization wave that propagates across the cerebral gray matter transiently suppressing neuronal activity. Prophylactic treatments for migraine, such as topiramate or valproate, reduce the number of CSD events. We evaluated changes in gene expression in rat cortex and brainstem after inducing CSD in the cortex, with and without a prophylactic treatment with topiramate or valproate. CSD induction showed similar transcriptomic profiles with and without treatment in cortex, involving genes related to hormone stimulus, apoptosis, synaptic transmission, and interleukin signaling. In brainstem, CSD with and without treatment, although to a lesser extent, also induced gene expression changes involving genes related to apoptosis. Half of the genes altered in brainstem after CSD were also differentially expressed in the same direction in cortex. No differences in gene expression were identified after CSD as a consequence of the treatments, neither in cortex nor in brainstem. Our results suggest that early after triggering the CSD, similar consequences are seen at the genetic level with or without prophylactic treatment. Gene expression changes induced by CSD in cortex and brainstem may help to better understand the underlying mechanisms and identify targets for therapeutic approaches. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  7. Dynamic diameter response of intraparenchymal penetrating arteries during cortical spreading depression and elimination of vasoreactivity to hypercapnia in anesthetized mice.

    PubMed

    Unekawa, Miyuki; Tomita, Yutaka; Masamoto, Kazuto; Toriumi, Haruki; Osada, Takashi; Kanno, Iwao; Suzuki, Norihiro

    2017-02-01

    Cortical spreading depression (CSD) induces marked hyperemia with a transient decrease of regional cerebral blood flow (rCBF), followed by sustained oligemia. To further understand the microcirculatory mechanisms associated with CSD, we examined the temporal changes of diameter of intraparenchymal penetrating arteries during CSD. In urethane-anesthetized mice, the diameter of single penetrating arteries at three depths was measured using two-photon microscopy during passage of repeated CSD, with continuous recordings of direct current potential and rCBF. The first CSD elicited marked constriction superimposed on the upstrokes of profound dilation throughout each depth of the penetrating artery, and the vasoreaction temporally corresponded to the change of rCBF. Second or later CSD elicited marked dilation with little or no constriction phase throughout each depth, and the vasodilation also temporally corresponded to the increase of rCBF. Furthermore, the peak dilation showed good negative correlations with basal diameter and increase of rCBF. Vasodilation induced by 5% CO2 inhalation was significantly suppressed after CSD passage at any depth as well as hyperperfusion. These results may indicate that CSD-induced rCBF changes mainly reflect the diametric changes of the intraparenchymal arteries, despite the elimination of responsiveness to hypercapnia.

  8. Cortical spreading depression in the feline brain following sustained and transient stimuli studied using diffusion-weighted imaging

    PubMed Central

    Bradley, Daniel P; Smith, Justin M; Smith, Martin I; Bockhorst, Kurt H-J; Papadakis, Nikolas G; Hall, Laurance D; Parsons, Andrew A; James, Michael F; Huang, Christopher L-H

    2002-01-01

    Cortical spreading depression (CSD) was induced by transient (10 min) applications of KCl in agar upon the cortical surface of α-chloralose anaesthetised cats. Its features were compared with CSD resulting from sustained applications of crystalline KCl through a mapping of the apparent diffusion coefficient (ADC) using diffusion-weighted echo planar imaging (DWI) over a poststimulus period of 60–100 min. Individual CSD events were computationally detected with the aid of Savitzky-Golay smoothing applied to critically sampled data derived from regions of interest (ROIs) made up of 2 × 2 pixel matrices. The latter were consistently placed at three selected sites on the suprasylvian gyrus (SG) and six sites on the marginal gyrus (MG). The CSD events thus detected were then quantitatively characterised for each ROI using the original time series. Both stimuli consistently elicited similar spreading patterns of initial, primary CSD events that propagated over the SG and marginal MG and were restricted to the hemispheres on which the stimuli were applied. There followed secondary events over smaller extents of cortical surface. Sustained stimuli elicited primary and secondary CSD events with similar amplitudes of ADC deflection that were distributed around a single mean. The ADC deflections were also conserved in peak amplitude throughout the course of their propagation. The initial primary event showed a poststimulus latency of 1.1 ± 0.1 min. Successive secondary events followed at longer, but uniform, time intervals of around 10 min. Primary and secondary CSDs showed significantly different velocities of conduction (3.32 ± 0.43 mm min−1vs. 2.11 ± 0.21 mm min−1, respectively; n= 5) across the cerebral hemisphere. In contrast, transient stimuli produced significantly fewer numbers of CSD events (3.8 ± 0.5 events per animal, n= 5) than did sustained stimuli (7.4 ± 0.5 events per animal, mean ±s.e.m., n= 5, P= 0.002). The peak ADC deflection of their primary

  9. Collecting Autonomous Spreading Malware Using High-Interaction Honeypots

    NASA Astrophysics Data System (ADS)

    Zhuge, Jianwei; Holz, Thorsten; Han, Xinhui; Song, Chengyu; Zou, Wei

    Autonomous spreading malware in the form of worms or bots has become a severe threat in today's Internet. Collecting the sample as early as possible is a necessary precondition for the further treatment of the spreading malware, e.g., to develop antivirus signatures. In this paper, we present an integrated toolkit called HoneyBow, which is able to collect autonomous spreading malware in an automated manner using high-interaction honeypots. Compared to low-interaction honeypots, HoneyBow has several advantages due to a wider range of captured samples and the capability of collecting malware which propagates by exploiting new vulnerabilities. We validate the properties of HoneyBow with experimental data collected during a period of about nine months, in which we collected thousands of malware binaries. Furthermore, we demonstrate the capability of collecting new malware via a case study of a certain bot.

  10. Cortical Spreading Depression Promotes Persistent Mechanical Sensitization of Intracranial Meningeal Afferents: Implications for the Intracranial Mechanosensitivity of Migraine

    PubMed Central

    Zhao, Jun

    2016-01-01

    Abstract Migraine is one of the most common and disabling diseases in the world. A major feature of migraine headache is its aggravation by maneuvers that momentarily increase intracranial pressure. A key hypothesis implicates mechanical sensitization of trigeminal afferents that innervate the intracranial meninges in mediating this feature of migraine. However, whether such pain-related neural response actually develops under endogenous conditions that are linked specifically to migraine remains to be established. Single-unit recordings in the trigeminal ganglion of anesthetized male rats were combined with quantitative mechanical stimulation of the cranial dura mater to determine whether cortical spreading depression (CSD), an endogenous migraine-triggering event, affects the mechanosensitivity of meningeal afferents. CSD gave rise to an almost threefold increase in the magnitude of the responses to mechanical stimuli in 17 of 23 of the afferents tested. CSD-evoked meningeal afferent mechanosensitization occurred with a delay of 23.1 ± 2.2 min and lasted 64.1 ± 6.8 min in recording sessions that lasted for 90 min and for 177.5 ± 22.1 min in recording sessions that were extended for 240 min. Some of the sensitized afferents also developed a shorter-lasting increase in their ongoing discharge rate that was not correlated with the increase in their mechanosensitivity, suggesting that CSD-evoked meningeal afferent sensitization and increase in ongoing activity are independent phenomena. These novel findings support the notion that mechanical sensitization of meningeal afferents serves as a key nociceptive process that underlies the worsening of migraine headache during conditions that momentarily increase intracranial pressure. PMID:28127585

  11. The axial topographic high at intermediate and fast spreading ridges

    NASA Astrophysics Data System (ADS)

    Carbotte, Suzanne M.; MacDonald, Ken C.

    1994-12-01

    An axial topographic high is commonly observed at both fast spreading ridges and some segments of intermediate spreading ridges. At fast rates the axial high is primarily created by the buoyancy of hot rock and magma beneath the rise. As newly formed crust is transported off axis, little vestige of an axial high is observed on the ridge flanks. In contrast, at intermediate rates, a significant component of the positive topography may be a volcanic construction, preserved on the ridge flanks as abyssal hills, which are slit axial volcanoes. We suggest this difference in the nature of the axial high reflects a lithosphere strong enough to support construction of a volcanic crestal ridge at intermediate spreading rates, but only rarely at fast rates. Relict overlap ridges, found within the discordant zones left by overlapping spreading centers, is one class of ridge-flank topography which appears to have a significant volcanic constructional component even at fast spreading ridges. Unlike topography away from these discontinuities, the relief and shape of overlapping spreading centers is preserved as relict ridge tips are rafted onto the ridge flanks. Reduced magma supply at these discontinuities may give rise to an axial lithosphere strong enough to support volcanic construction of overlap ridges. Low axial lithospheric strength may also account for the lack of normal faults within the innermost 1-2 km of fast, and some intermediate, spreading ridges. With a thin/weak brittle layer at the ridge crest, tensile failure will predominate and few normal faults will form. Depths to the axial magma chamber reflector observed in multi-channel seismic data limit the thickness of the brittel layer on axis to less than 1-2 km for much of the East Pacific Rise (EPR). This depth is comparable to depths over which tensile failure within the oceanic crust will predominate, estimated from the Griffith criteria for fracture initiation (approx. 0.5-1.5 km). As the brittle layer

  12. Up-regulated neuronal COX-2 expression after cortical spreading depression is involved in non-REM sleep induction in rats.

    PubMed

    Cui, Yilong; Kataoka, Yosky; Inui, Takashi; Mochizuki, Takatoshi; Onoe, Hirotaka; Matsumura, Kiyoshi; Urade, Yoshihiro; Yamada, Hisao; Watanabe, Yasuyoshi

    2008-03-01

    Cortical spreading depression is an excitatory wave of depolarization spreading throughout cerebral cortex at a rate of 2-5 mm/min and has been implicated in various neurological disorders, such as epilepsy, migraine aura, and trauma. Although sleepiness or sleep is often induced by these neurological disorders, the cellular and molecular mechanism has remained unclear. To investigate whether and how the sleep-wake behavior is altered by such aberrant brain activity, we induced cortical spreading depression in freely moving rats, monitoring REM and non-REM (NREM) sleep and sleep-associated changes in cyclooxygenase (COX)-2 and prostaglandins (PGs). In such a model for aberrant neuronal excitation in the cerebral cortex, the amount of NREM sleep, but not of REM sleep, increased subsequently for several hours, with an up-regulated expression of COX-2 in cortical neurons and considerable production of PGs. A specific inhibitor of COX-2 completely arrested the increase in NREM sleep. These results indicate that up-regulated neuronal COX-2 would be involved in aberrant brain excitation-induced NREM sleep via production of PGs.

  13. Characterization of cortical spreading depression in adult well-nourished and malnourished rats submitted to the association of pilocarpine-induced epilepsy plus streptozotocin-induced hyperglycemia.

    PubMed

    Costa-Cruz, Raquel Raimunda Goldstein; Amâncio-dos-Santos, Angela; Guedes, Rubem Carlos Araújo

    2006-07-03

    Spreading depression was characterized in adult rats rendered epileptic by pilocarpine (350 mg/kg, i.p.) and thereafter made hyperglycemic with (i.p.) 60 mg/kg streptozotocin. Groups treated with only one of the above drugs, as well as control groups treated with their vehicles (saline and citrate buffer, respectively) were also studied. The animals treated with pilocarpine or streptozotocin presented, as a common feature, a reduction in the spreading depression propagation rate. However, they differed by the fact that pilocarpine, in some cases, blocked spreading depression propagation, whereas streptozotocin did not block it at all. In early-malnourished animals, streptozotocin-effects, but not pilocarpine-effects on spreading depression were attenuated. The treatment with both drugs did not potentiate their individual reducing effects on spreading depression propagation, irrespective of the animals' early nutritional status. These results extend previous observations on rats treated with both drugs separately, confirming their impairing action on spreading depression propagation. They also indicate that early malnutrition is more effective in changing the streptozotocin effects on spreading depression, as compared to the pilocarpine-effects. Since such effects were observed at adulthood, they indicate that the early malnutrition-induced cortical changes responsible for the here-described effects are long-lasting.

  14. In Vivo Voltage-Sensitive Dye Study of Lateral Spreading of Cortical Activity in Mouse Primary Visual Cortex Induced by a Current Impulse

    PubMed Central

    Fehérvári, Tamás Dávid; Sawai, Hajime; Yagi, Tetsuya

    2015-01-01

    In the mammalian primary visual cortex (V1), lateral spreading of excitatory potentials is believed to be involved in spatial integrative functions, but the underlying cortical mechanism is not well understood. Visually-evoked population-level responses have been shown to propagate beyond the V1 initial activation site in mouse, similar to higher mammals. Visually-evoked responses are, however, affected by neuronal circuits prior to V1 (retina, LGN), making the separate analysis of V1 difficult. Intracortical stimulation eliminates these initial processing steps. We used in vivo RH1691 voltage-sensitive dye (VSD) imaging and intracortical microstimulation in adult C57BL/6 mice to elucidate the spatiotemporal properties of population-level signal spreading in V1 cortical circuits. The evoked response was qualitatively similar to that measured in single-cell electrophysiological experiments in rodents: a fast transient fluorescence peak followed by a fast and a slow decrease or hyperpolarization, similar to EPSP and fast and slow IPSPs in single cells. The early cortical response expanded at speeds commensurate with long horizontal projections (at 5% of the peak maximum, 0.08–0.15 m/s) however, the bulk of the VSD signal propagated slowly (at half-peak maximum, 0.05–0.08 m/s) suggesting an important role of regenerative multisynaptic transmission through short horizontal connections in V1 spatial integrative functions. We also found a tendency for a widespread and fast cortical response suppression in V1, which was eliminated by GABAA-antagonists gabazine and bicuculline methiodide. Our results help understand the neuronal circuitry involved in lateral spreading in V1. PMID:26230520

  15. Device for simultaneous positron emission tomography, laser speckle imaging and RGB reflectometry: validation and application to cortical spreading depression and brain ischemia in rats.

    PubMed

    Gramer, M; Feuerstein, D; Steimers, A; Takagaki, M; Kumagai, T; Sué, M; Vollmar, S; Kohl-Bareis, M; Backes, H; Graf, R

    2014-07-01

    Brain function critically relies on the supply with energy substrates (oxygen and glucose) via blood flow. Alterations in energy demand as during neuronal activation induce dynamic changes in substrate fluxes and blood flow. To study the complex system that regulates cerebral metabolism requires the combination of methods for the simultaneous assessment of multiple parameters. We developed a multimodal imaging device to combine positron emission tomography (PET) with laser speckle imaging (LSI) and RGB reflectometry (RGBR). Depending on the radiotracer, PET provides 3-dimensional quantitative information of specific molecular processes, while LSI and RGBR measure cerebral blood flow (CBF) and hemoglobin oxygenation at high temporal and spatial resolution. We first tested the functional capability of each modality within our system and showed that interference between the modalities is negligible. We then cross-calibrated the system by simultaneously measuring absolute CBF using (15)O-H2O PET (CBF(PET)) and the inverse correlation time (ICT), the LSI surrogate for CBF. ICT and CBF(PET) correlated in multiple measurements in individuals as well as across different animals (R(2)=0.87, n=44 measurements) indicating that ICT can be used for absolute quantitative assessment of CBF. To demonstrate the potential of the combined system, we applied it to cortical spreading depression (CSD), a wave of transient cellular depolarization that served here as a model system for neurovascular and neurometabolic coupling. We analyzed time courses of hemoglobin oxygenation and CBF alterations coupled to CSD, and simultaneously measured regional uptake of (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) used as a radiotracer for regional glucose metabolism, in response to a single CSD and to a cluster of CSD waves. With this unique combination, we characterized the changes in cerebral metabolic rate of oxygen (CMRO2) in real-time and showed a correlation between (18)F-FDG uptake and the

  16. RECOGNIZE: A Social Norms Campaign to Reduce Rumor Spreading in a Junior High School

    ERIC Educational Resources Information Center

    Cross, Jennifer E.; Peisner, William

    2009-01-01

    This article studied changes in rumor spreading and perceptions of peers' rumor spreading among students at one public junior high school following a social norms marketing campaign. Results of the study show that perceptions of peer rumor spreading fell following the campaign, but self-reports of rumor spreading did not decrease. Results suggest…

  17. RECOGNIZE: A Social Norms Campaign to Reduce Rumor Spreading in a Junior High School

    ERIC Educational Resources Information Center

    Cross, Jennifer E.; Peisner, William

    2009-01-01

    This article studied changes in rumor spreading and perceptions of peers' rumor spreading among students at one public junior high school following a social norms marketing campaign. Results of the study show that perceptions of peer rumor spreading fell following the campaign, but self-reports of rumor spreading did not decrease. Results suggest…

  18. Potassium-induced cortical spreading depression bilaterally suppresses the electroencephalogram but only ipsilaterally affects red blood cell velocity in intraparenchymal capillaries.

    PubMed

    Unekawa, Miyuki; Tomita, Yutaka; Toriumi, Haruki; Masamoto, Kazuto; Kanno, Iwao; Suzuki, Norihiro

    2013-04-01

    Cortical spreading depression (CSD) is a repetitive, propagating profile of mass depolarization of neuronal and glial cells, followed by sustained suppression of spontaneous neuronal activity. We have reported a long-lasting suppressive effect on red blood cell (RBC) velocities in intraparenchymal capillaries. Here, to test the hypothesis that the prolonged decrease of RBC velocity in capillaries is due to suppression of neuronal activity, we measured CSD-elicited changes in the electroencephalogram (EEG) as an index of neuronal activity. In isoflurane-anesthetized rats, DC potential, EEG, partial pressure of oxygen (PO₂), and cerebral blood flow (CBF) were simultaneously recorded in the temporo-parietal region. The velocities of fluorescently labeled RBCs were evaluated by high-speed camera laser scanning confocal fluorescence microscopy with our original software, KEIO-IS2. Transient deflection of DC potential and PO₂ and increase of CBF were repeatedly detected only in the ipsilateral hemisphere following topical KCl application. On the other hand, the relative spectral power of EEG was reduced bilaterally, showing the lowest value at 5 min after KCl application, when the other parameters had already returned to the baseline after the passage of CSD. Mean RBC velocity in capillaries was slightly but significantly reduced during and after passage of CSD in the ipsilateral hemisphere but did not change in the contralateral hemisphere in the same rats. We suggest that mass depolarization of neuronal and glial cells might transiently decelerate RBCs in nearby capillaries, but the sustained reduction of ipsilateral RBC velocity might be a result of the prolonged effect of CSD, not of neuronal suppression alone. Copyright © 2013 Wiley Periodicals, Inc.

  19. Mapping of cortical activity in the first two decades of life: a high-density sleep electroencephalogram study.

    PubMed

    Kurth, Salomé; Ringli, Maya; Geiger, Anja; LeBourgeois, Monique; Jenni, Oskar G; Huber, Reto

    2010-10-06

    Evidence that electroencephalography (EEG) slow-wave activity (SWA) (EEG spectral power in the 1-4.5 Hz band) during non-rapid eye movement sleep (NREM) reflects plastic changes is increasing (Tononi and Cirelli, 2006). Regional assessment of gray matter development from neuroimaging studies reveals a posteroanterior trajectory of cortical maturation in the first three decades of life (Shaw et al., 2008). Our aim was to test whether this regional cortical maturation is reflected in regional changes of sleep SWA. We evaluated all-night high-density EEG (128 channels) in 55 healthy human subjects (2.4-19.4 years) and assessed age-related changes in NREM sleep topography. As in adults, we observed frequency-specific topographical distributions of sleep EEG power in all subjects. However, from early childhood to late adolescence, the location on the scalp showing maximal SWA underwent a shift from posterior to anterior regions. This shift along the posteroanterior axis was only present in the SWA frequency range and remained stable across the night. Changes in the topography of SWA during sleep parallel neuroimaging study findings indicating cortical maturation starts early in posterior areas and spreads rostrally over the frontal cortex. Thus, SWA might reflect the underlying processes of cortical maturation. In the future, sleep SWA assessments may be used as a clinical tool to detect aberrations in cortical maturation.

  20. Do the accelerating actions of tianeptine and l-arginine on cortical spreading depression interact? An electrophysiological analysis in young and adult rats.

    PubMed

    Maia, Luciana Maria Silva de Seixas; Amancio-Dos-Santos, Angela; Germano, Paula Catirina Pereira da Silva; Falcão, Anna Carolina Santos Marinho; Duda-de-Oliveira, Desirré; Guedes, Rubem Carlos Araújo

    2017-05-22

    In the rat, we previously demonstrated that serotonin-enhancing drugs impair cortical spreading depression (CSD) and that l-arginine (arginine) treatment enhances CSD. Here, we investigated the interaction between topical application of the serotonin uptake enhancer tianeptine and systemic arginine administration on CSD. From postnatal day 7-28, female Wistar rats (n=40) received by gavage 300mg/Kg/day arginine (n=20) or water (n=20). Half of the arginine- or water-treated rats underwent CSD recording at 30-40days of age (young), while the other half was recorded at 90-120days (adult). Following baseline recording (four episodes of CSD), we applied tianeptine solution (10mg/ml) to a rectangular portion of the intact dura mater for 10-min and then elicited CSD. This procedure was repeated three times. Compared to baseline values, CSD velocities and amplitudes following tianeptine application increased, and CSD duration decreased significantly (p<0.05) in both young and adult rats, regardless of treatment group. CSD acceleration caused by systemic treatment with arginine is in agreement with previous findings. Topical cortical application of tianeptine replicated the effect of systemic application, suggesting a cortically based mechanism for tianeptine's action. However, the absence of interaction between arginine and tianeptine treatments suggests that they probably act through separate mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Potentiation of spontaneous and evoked cortical electrical activity after spreading depression: in vivo analysis in well-nourished and malnourished rats.

    PubMed

    de Souza, Thays Kallyne Marinho; e Silva, Mariana Barros; Gomes, André Ricardson; de Oliveira, Hélio Magalhães; Moraes, Renato Barros; de Freitas Barbosa, Catão Temístocles; Guedes, Rubem Carlos Araújo

    2011-10-01

    Cortical spreading depression (CSD) is influenced by brain excitability and is related to neurological diseases, such as epilepsy. In vitro evidence indicates that neuronal electrical activity is potentiated after CSD. Malnutrition can cause electrophysiological changes in the brain, both in animals and in humans. Here, we investigated in vivo whether CSD potentiates the amplitude of electrocorticogram (ECoG) and of transcallosal evoked responses in adult well-nourished (W), early-malnourished (M), and food-restricted rats. ECoG amplitudes were compared before and after CSD, at two parietal regions (designated the anterior and posterior regions). In the anterior region, post-CSD amplitudes of the ECoG waves were 13-23% higher (P < 0.05) than the pre-CSD values in all groups. In the posterior region, amplitudes increased 22% in the M group only (P < 0.05). In a fourth CSD-free group, ECoG amplitude did not change during the four recording hours. Transcallosal electrically evoked cortical responses also increased 21.5 ± 9.6% and 41.8 ± 28.5%, after CSD, in the W and M conditions, respectively, as compared to pre-CSD values. The data support the hypothesis of an in vivo CSD potentiation on cortical excitability as recorded by spontaneous and evoked electrical activity and modulation by nutritional status.

  2. Spreading of Viscous Liquids at High Temperature: Silicate Glasseson Molybdenum

    SciTech Connect

    Lopez-Esteban, Sonia; Saiz, Eduardo; Moya, Jose S.; Tomsia,Antoni P.

    2004-12-15

    The spreading of Si-Ca-Al-Ti-O glasses on molybdenum has been investigated. By controlling the oxygen activity in the furnace, spreading can take place under reactive or non-reactive conditions. As the nucleation of the reaction product under reactive conditions is slow in comparison to the spreading kinetics, in both cases the glass front moves on the metal surface with similar spreading velocities. Spreading can be described using a molecular dynamics model where the main contribution to the wetting activation energy comes from the viscous interactions in the liquid. Enhanced interfacial diffusions in low-oxygen activities (reactive cases) form triple-line ridges that can pin the wetting front and cause a stick-slip motion.

  3. Lasting facilitatory effects of neonatal vibrissae removal on the propagation of cortical spreading depression: an electrophysiological study in well-nourished and early-malnourished adult rats.

    PubMed

    Tenório, Angélica da Silva; Moura, Fábia Rossana da Silva; Silva, Levy Petrus Silvestre de Lima; Guedes, Rubem Carlos Araújo

    2009-12-01

    Early malnutrition interferes with the formation of somatosensory pathways and reduced sensory input activity during brain development can induce morphological and physiological changes in the cerebral cortex, altering their response properties in the long-term. Here, we investigated cortical spreading depression (CSD) propagation in male adult rats submitted to unilateral vibrissae removal, at postnatal days 2-3, and malnourished during lactation followed by nutritional recovery until adulthood (90-120 days), when CSD was recorded. Compared to nutrition-matched non-lesioned controls, CSD-propagation was increased in the hemisphere contralateral to the vibrissae removal. The findings indicate that vibrissae removal during brain development enhances CSD-propagation, and early malnutrition did not modify this effect. Considering that CSD-facilitation persisted until adulthood, we suggest that this effect is permanent. The data might contribute to the understanding of the mechanisms by which sensory input deprivation-induced plasticity modifies cerebral electrophysiological responses in the developing brain.

  4. Enhanced excitatory transmission at cortical synapses as the basis for facilitated spreading depression in Ca(v)2.1 knockin migraine mice.

    PubMed

    Tottene, Angelita; Conti, Rossella; Fabbro, Alessandra; Vecchia, Dania; Shapovalova, Maryna; Santello, Mirko; van den Maagdenberg, Arn M J M; Ferrari, Michel D; Pietrobon, Daniela

    2009-03-12

    Migraine is a common disabling brain disorder. A subtype of migraine with aura (familial hemiplegic migraine type 1: FHM1) is caused by mutations in Ca(V)2.1 (P/Q-type) Ca(2+) channels. Knockin mice carrying a FHM1 mutation show increased neuronal P/Q-type current and facilitation of induction and propagation of cortical spreading depression (CSD), the phenomenon that underlies migraine aura and may activate migraine headache mechanisms. We studied cortical neurotransmission in neuronal microcultures and brain slices of FHM1 mice. We show gain of function of excitatory neurotransmission due to increased action-potential-evoked Ca(2+) influx and increased probability of glutamate release at pyramidal cell synapses but unaltered inhibitory neurotransmission at fast-spiking interneuron synapses. Using an in vitro model of CSD, we show a causative link between enhanced glutamate release and CSD facilitation. The synapse-specific effect of FHM1 mutations points to disruption of excitation-inhibition balance and neuronal hyperactivity as the basis for episodic vulnerability to CSD ignition in migraine.

  5. Construction of 4D high-definition cortical surface atlases of infants: Methods and applications.

    PubMed

    Li, Gang; Wang, Li; Shi, Feng; Gilmore, John H; Lin, Weili; Shen, Dinggang

    2015-10-01

    In neuroimaging, cortical surface atlases play a fundamental role for spatial normalization, analysis, visualization, and comparison of results across individuals and different studies. However, existing cortical surface atlases created for adults are not suitable for infant brains during the first two postnatal years, which is the most dynamic period of postnatal structural and functional development of the highly-folded cerebral cortex. Therefore, spatiotemporal cortical surface atlases for infant brains are highly desired yet still lacking for accurate mapping of early dynamic brain development. To bridge this significant gap, leveraging our infant-dedicated computational pipeline for cortical surface-based analysis and the unique longitudinal infant MRI dataset acquired in our research center, in this paper, we construct the first spatiotemporal (4D) high-definition cortical surface atlases for the dynamic developing infant cortical structures at seven time points, including 1, 3, 6, 9, 12, 18, and 24 months of age, based on 202 serial MRI scans from 35 healthy infants. For this purpose, we develop a novel method to ensure the longitudinal consistency and unbiasedness to any specific subject and age in our 4D infant cortical surface atlases. Specifically, we first compute the within-subject mean cortical folding by unbiased groupwise registration of longitudinal cortical surfaces of each infant. Then we establish longitudinally-consistent and unbiased inter-subject cortical correspondences by groupwise registration of the geometric features of within-subject mean cortical folding across all infants. Our 4D surface atlases capture both longitudinally-consistent dynamic mean shape changes and the individual variability of cortical folding during early brain development. Experimental results on two independent infant MRI datasets show that using our 4D infant cortical surface atlases as templates leads to significantly improved accuracy for spatial normalization

  6. Perfusion pressure-dependent recovery of cortical spreading depression is independent of tissue oxygenation over a wide physiologic range.

    PubMed

    Sukhotinsky, Inna; Yaseen, Mohammad A; Sakadzić, Sava; Ruvinskaya, Svetlana; Sims, John R; Boas, David A; Moskowitz, Michael A; Ayata, Cenk

    2010-06-01

    Spreading depression (SD) is a slowly propagating wave of transient neuronal and glial depolarization that develops after stroke, trauma and subarachnoid hemorrhage. In compromised tissue, repetitive SD-like injury depolarizations reduce tissue viability by worsening the mismatch between blood flow and metabolism. Although the mechanism remains unknown, SDs show delayed electrophysiological recovery within the ischemic penumbra. Here, we tested the hypothesis that the recovery rate of SD can be varied by modulating tissue perfusion pressure and oxygenation. Systemic blood pressure and arterial pO(2) were simultaneously manipulated in anesthetized rats under full physiologic monitoring. We found that arterial hypotension doubled the SD duration, whereas hypertension reduced it by a third compared with normoxic normotensive rats. Hyperoxia failed to shorten the prolonged SD durations in hypotensive rats, despite restoring tissue pO(2). Indeed, varying arterial pO(2) (40 to 400 mm Hg) alone did not significantly influence SD duration, whereas blood pressure (40 to 160 mm Hg) was inversely related to SD duration in compromised tissue. These data suggest that cerebral perfusion pressure is a critical determinant of SD duration independent of tissue oxygenation over a wide range of arterial pO(2) levels, and that hypotension may be detrimental in stroke and subarachnoid hemorrhage, where SD-like injury depolarizations have been observed.

  7. Comparative potency of sensory-induced brainstem activation to trigger spreading depression and seizures in the cortex of awake rats: Implications for the pathophysiology of migraine aura.

    PubMed

    Vinogradova, Lyudmila V

    2015-10-01

    Migraine and epilepsy are highly co-morbid neurological disorders associated with episodic dysfunction of both cortical and subcortical networks. The study examined the interrelation between cortical spreading depression, the electrophysiological correlate of migraine aura and seizures triggered at cortical and brainstem levels by repeated sound stimulation in rats with acoustic hypersensitivity (reflex audiogenic epilepsy). In awake, freely moving rats with innate audiogenic epilepsy, 25 episodes of running seizure (brainstem seizures) were induced by repeated sound stimulation. Spreading depression and seizures were recorded using implanted cortical electrodes. The first sound-induced brainstem seizures evoked neither spreading depression nor seizures in the cortex. With repetition, brainstem seizures began to be followed by a single cortical spreading depression wave and an epileptiform discharge. Spreading depression was more frequent an early cortical event than seizures: spreading depression appeared after 8.4 ± 1.0 repeated stimulations in 100% rats (n = 24) while cortical seizures were recorded after 12.9 ± 1.2 tests in 46% rats. Brainstem seizure triggered unilateral long-latency spreading depression. Bilateral short-latency cortical spreading depression was recorded only after intense cortical seizures. These data show that episodic brainstem activation is a potent trigger of unilateral cortical spreading depression. Development of intense seizures in the cortex leads to initiation of spreading depression in multiple cortical sites of both hemispheres. © International Headache Society 2014.

  8. Low and High-Frequency Field Potentials of Cortical Networks ...

    EPA Pesticide Factsheets

    Neural networks grown on microelectrode arrays (MEAs) have become an important, high content in vitro assay for assessing neuronal function. MEA experiments typically examine high- frequency (HF) (>200 Hz) spikes, and bursts which can be used to discriminate between different pharmacological agents/chemicals. However, normal brain activity is additionally composed of integrated low-frequency (0.5-100 Hz) field potentials (LFPs) which are filtered out of MEA recordings. The objective of this study was to characterize the relationship between HF and LFP neural network signals, and to assess the relative sensitivity of LFPs to selected neurotoxicants. Rat primary cortical cultures were grown on glass, single-well MEA chips. Spontaneous activity was sampled at 25 kHz and recorded (5 min) (Multi-Channel Systems) from mature networks (14 days in vitro). HF (spike, mean firing rate, MFR) and LF (power spectrum, amplitude) components were extracted from each network and served as its baseline (BL). Next, each chip was treated with either 1) a positive control, bicuculline (BIC, 25μM) or domoic acid (DA, 0.3μM), 2) or a negative control, acetaminophen (ACE, 100μM) or glyphosate (GLY, 100μM), 3) a solvent control (H2O or DMSO:EtOH), or 4) a neurotoxicant, (carbaryl, CAR 5, 30μM ; lindane, LIN 1, 10μM; permethrin, PERM 25, 50μM; triadimefon, TRI 5, 65μM). Post treatment, 5 mins of spontaneous activity was recorded and analyzed. As expected posit

  9. Neonatal L-glutamine modulates anxiety-like behavior, cortical spreading depression, and microglial immunoreactivity: analysis in developing rats suckled on normal size- and large size litters.

    PubMed

    de Lima, Denise Sandrelly Cavalcanti; Francisco, Elian da Silva; Lima, Cássia Borges; Guedes, Rubem Carlos Araújo

    2017-02-01

    In mammals, L-glutamine (Gln) can alter the glutamate-Gln cycle and consequently brain excitability. Here, we investigated in developing rats the effect of treatment with different doses of Gln on anxiety-like behavior, cortical spreading depression (CSD), and microglial activation expressed as Iba1-immunoreactivity. Wistar rats were suckled in litters with 9 and 15 pups (groups L 9 and L 15; respectively, normal size- and large size litters). From postnatal days (P) 7-27, the animals received Gln per gavage (250, 500 or 750 mg/kg/day), or vehicle (water), or no treatment (naive). At P28 and P30, we tested the animals, respectively, in the elevated plus maze and open field. At P30-35, we measured CSD parameters (velocity of propagation, amplitude, and duration). Fixative-perfused brains were processed for microglial immunolabeling with anti-IBA-1 antibodies to analyze cortical microglia. Rats treated with Gln presented an anxiolytic behavior and accelerated CSD propagation when compared to the water- and naive control groups. Furthermore, CSD velocity was higher (p < 0.001) in the L 15 compared to the L 9 condition. Gln treatment increased Iba1 immunolabeling both in the parietal cortex and CA1 hippocampus, indicating microglial activation. The Gln effect was dose-dependent for anxiety-like behavior and CSD in both litter sizes, and for microglial activation in the L 15 groups. Besides confirming previous electrophysiological findings (CSD acceleration after Gln), our data demonstrate for the first time a behavioral and microglial activation that is associated with early Gln treatment in developing animals, and that is possibly operated via changes in brain excitability.

  10. High levels of neuroticism are associated with decreased cortical folding of the dorsolateral prefrontal cortex.

    PubMed

    Christoph Schultz, C; Warziniak, Heide; Koch, Kathrin; Schachtzabel, Claudia; Güllmar, Daniel; Reichenbach, Jürgen R; Schlösser, Ralf G; Sauer, Heinrich; Wagner, Gerd

    2017-04-06

    The personality trait neuroticism has been identified as a vulnerability factor for common psychiatric diseases and defining potential neuroanatomical markers for early recognition and prevention strategies is mandatory. Because both personality traits and cortical folding patterns are early imprinted and timely stable there is reason to hypothesize an association between neuroticism and cortical folding. Thus, to identify a putative linkage, we tested whether the degree of neuroticism is associated with local cortical folding in a sample of 109 healthy individuals using a surface-based MRI approach. Based on previous findings we additionally tested for a potential association with cortical thickness. We found a highly significant negative correlation between the degree of neuroticism and local cortical folding of the left dorsolateral prefrontal cortex (DLPFC), i.e., high levels of neuroticism were associated with low cortical folding of the left DLPFC. No association was found with cortical thickness. The present study is the first to describe a linkage between the extent of local cortical folding and the individual degree of neuroticism in healthy subjects. Because neuroticism is a vulnerability factor for common psychiatric diseases such as depression our finding indicates that alterations of DLPFC might constitute a neurobiological marker elevating risk for psychiatric burden.

  11. l-Citrulline ameliorates cerebral blood flow during cortical spreading depression in rats: Involvement of nitric oxide- and prostanoids-mediated pathway.

    PubMed

    Kurauchi, Yuki; Mokudai, Koichi; Mori, Asami; Sakamoto, Kenji; Nakahara, Tsutomu; Morita, Masahiko; Kamimura, Ayako; Ishii, Kunio

    2017-02-17

    l-Citrulline is a potent precursor of l-arginine, and exerts beneficial effect on cardiovascular system via nitric oxide (NO) production. Migraine is one of the most popular neurovascular disorder, and imbalance of cerebral blood flow (CBF) observed in cortical spreading depression (CSD) contributes to the mechanism of migraine aura. Here, we investigated the effect of l-citrulline on cardiovascular changes to KCl-induced CSD. in rats. Intravenous injection of l-citrulline prevented the decrease in CBF, monitored by laser Doppler flowmetry, without affecting mean arterial pressure and heart rate during CSD. Moreover, l-citrulline attenuated propagation velocity of CSD induced by KCl. The effect of l-citrulline on CBF change was prevented by l-NAME, an inhibitor of NO synthase, but not by indomethacin, an inhibitor of cyclooxygenase. On the other hand, attenuation effect of l-citrulline on CSD propagation velocity was prevented not only by l-NAME but also by indomethacin. In addition, propagation velocity of CSD was attenuated by intravenous injection of NOR3, a NO donor, which was diminished by ODQ, an inhibitor of soluble guanylyl cyclase. These results suggest that NO/cyclic GMP- and prostanoids-mediated pathway differently contribute to the effect of l-citrulline on the maintenance of CBF.

  12. Modeling the contributions of Ca2+ flows to spontaneous Ca2+ oscillations and cortical spreading depression-triggered Ca2+ waves in astrocyte networks.

    PubMed

    Li, Bing; Chen, Shangbin; Zeng, Shaoqun; Luo, Qingming; Li, Pengcheng

    2012-01-01

    Astrocytes participate in brain functions through Ca(2+) signals, including Ca(2+) waves and Ca(2+) oscillations. Currently the mechanisms of Ca(2+) signals in astrocytes are not fully clear. Here, we present a computational model to specify the relative contributions of different Ca(2+) flows between the extracellular space, the cytoplasm and the endoplasmic reticulum of astrocytes to the generation of spontaneous Ca(2+) oscillations (CASs) and cortical spreading depression (CSD)-triggered Ca(2+) waves (CSDCWs) in a one-dimensional astrocyte network. This model shows that CASs depend primarily on Ca(2+) released from internal stores of astrocytes, and CSDCWs depend mainly on voltage-gated Ca(2+) influx. It predicts that voltage-gated Ca(2+) influx is able to generate Ca(2+) waves during the process of CSD even after depleting internal Ca(2+) stores. Furthermore, the model investigates the interactions between CASs and CSDCWs and shows that the pass of CSDCWs suppresses CASs, whereas CASs do not prevent the generation of CSDCWs. This work quantitatively analyzes the generation of astrocytic Ca(2+) signals and indicates different mechanisms underlying CSDCWs and non-CSDCWs. Research on the different types of Ca(2+) signals might help to understand the ways by which astrocytes participate in information processing in brain functions.

  13. High-gravity spreading of liquid puddles on wetting flexible substrates

    NASA Astrophysics Data System (ADS)

    Yang, Chen; Burrous, Adam; Xie, Jingjin; Shaikh, Hassan; Elike-Avion, Akofa; Rojas Rodriguez, Luis; Ramachandran, Adithya; Choi, Wonjae; Mazzeo, Aaron D.

    2016-02-01

    This letter describes a mechanical approach of using high gravity to decrease the capillary length and increase the spreading rate of liquid puddles on wetting flexible substrates. By using centrifugation and a flexible substrate floating on a high-density liquid, uniform acceleration enhances the spreading of liquid puddles. Under high gravity of 600 g, the capillary length reduces by a factor of 24.5 to ˜60 μm. The reduction in capillary length results in gravity dominating the spreading of small puddles that would otherwise have slower spreading driven by both surface tension and gravity of 1 g. The resulting measurements suggest that derived expressions in the literature for gravity-driven spreading of puddles under earth's standard gravity extend to predicting the behavior of sufficiently large puddles spreading on flexible substrates exposed to more than 100 g of acceleration. This work explores the spreading of puddles/coatings under high gravity, and the techniques described in this work will allow further interrogation of the transition between surface tension- and gravity-driven spreading.

  14. Magnetic resonance imaging assessed cortical porosity is highly correlated with μCT porosity.

    PubMed

    Bae, Won C; Patil, Shantanu; Biswas, Reni; Li, Shihong; Chang, Eric Y; Statum, Sheronda; D'Lima, Darryl D; Chung, Christine B; Du, Jiang

    2014-09-01

    Cortical bone is typically regarded as "MR invisible" with conventional clinical magnetic resonance imaging (MRI) pulse sequences. However, recent studies have demonstrated that free water in the microscopic pores of cortical bone has a short T2* but a relatively long T2, and may be detectable with conventional clinical spin echo (SE) or fast spin echo (FSE) sequences. In this study we describe the use of a conventional two-dimensional (2D) FSE sequence to assess cortical bone microstructure and measure cortical porosity using a clinical 3T scanner. Twelve cadaveric human cortical bone samples were studied with MRI and microcomputed tomography (μCT) (downsampled to the same spatial resolution). Preliminary results show that FSE-determined porosity is highly correlated (R(2)=0.83; P<0.0001) with μCT porosity. Bland-Altman analysis suggested a good agreement between FSE and μCT with tight limit of agreement at around 3%. There is also a small bias of -2% for the FSE data, which suggested that the FSE approach slightly underestimated μCT porosity. The results demonstrate that cortical porosity can be directly assessed using conventional clinical FSE sequences. The clinical feasibility of this approach was also demonstrated on six healthy volunteers using 2D FSE sequences as well as 2D ultrashort echo time (UTE) sequences with a minimal echo time (TE) of 8μs, which provide high contrast imaging of cortical bone in vivo.

  15. Dose-dependent Cortical Thinning After Partial Brain Radiation in High-grade Glioma

    PubMed Central

    Karunamuni, Roshan; Bartsch, Hauke; White, Nate S.; Moiseenko, Vitali; Carmona, Ruben; Marshall, Deborah; Seibert, Tyler M.; McDonald, Carrie R.; Farid, Nikdokht; Krishnan, Anithapriya; Kuperman, Joshua; Mell, Loren; Brewer, James B.; Dale, Anders M.; Hattangadi-Gluth, Jona A.

    2015-01-01

    Purpose Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials We performed a voxel-wise analysis of MR imaging from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1-year post-RT. Cortex was parcellated with well-validated segmentation software (Freesufer). Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thickness between time points, RT dose value, and neuroanatomic label by lobe. Effect of dose, neuroanatomic location, age, and chemotherapy on cortical thickness was tested using linear mixed effects (LME) modeling. Results Cortical atrophy was seen after 1-year post RT, with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (p<0.001) for every 1 Gy increase in RT dose. Temporal and limbic cortex exhibited the largest change in cortical thickness per Gy, compared to other regions (p<0.001). Age and chemotherapy were not significantly associated with cortical thickness change. Conclusions We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, one year after fractionated partial brain RT. The magnitude of thinning parallels one-year atrophy rates seen in neurodegenerative diseases, and may contribute to cognitive decline following high-dose RT. PMID:26853338

  16. Estrogen-dependent effects of 5-hydroxytryptophan on cortical spreading depression in rat: Modelling the serotonin-ovarian hormone interaction in migraine aura.

    PubMed

    Chauvel, Virginie; Multon, Sylvie; Schoenen, Jean

    2017-01-01

    Background Cortical spreading depression (CSD) is the likely culprit of the migraine aura. Migraine is sexually dimorphic and thought to be a "low 5-HT" condition. We sought to decipher the interrelation between serotonin, ovarian hormones and cortical excitability in a model of migraine aura. Methods Occipital KCl-induced CSDs were recorded for one hour at parieto-occipital and frontal levels in adult male (n = 16) and female rats (n = 64) one hour after intraperitoneal (i.p.) injection of 5-hydroxytryptophan (5-HTP) or NaCl. Sixty-five oophorectomized females were treated with estradiol- (E2) or cholesterol- (Chol) filled capsules. Two weeks later we recorded CSDs after 5-HTP/NaCl injections before or 20 hours after capsule removal. Results 5-HTP had no effect in males, but decreased CSD frequency in cycling females, significantly so during estrus, at parieto-occipital (-3.5CSD/h, p < 0.001) and frontal levels (-2.5CSD/h, p = 0.014). In oophorectomized rats, CSD susceptibility increased during E2 treatment at both recording sites (+5CSD/h, p = 0.001 and +3CSD/h, p < 0.01), but decreased promptly after E2 withdrawal (-4.7CSD/h, p < 0.001 and -1.7CSD/h, p = 0.094). The CSD inhibitory effect of 5-HTP was significant only in E2-treated rats (-3.4CSD/h, p = 0.006 and -1.8CSD/h, p = 0.029). Neither the estrous cycle phase, nor E2 or 5-HTP treatments significantly modified CSD propagation velocity. Conclusion 5-HTP decreases CSD occurrence in the presence of ovarian hormones, suggesting its potential efficacy in migraine with aura prophylaxis in females. Elevated E2 levels increase CSD susceptibility, while estrogen withdrawal decreases CSD. In a translational perspective, these findings may explain why migraine auras can appear during pregnancy and why menstrual-related migraine attacks are rarely associated with an aura.

  17. Cortical thickness and surface area in neonates at high risk for schizophrenia

    PubMed Central

    Li, Gang; Wang, Li; Shi, Feng; Lyall, Amanda E.; Ahn, Mihye; Peng, Ziwen; Zhu, Hongtu; Lin, Weili; Gilmore, John H.

    2015-01-01

    Schizophrenia is a neurodevelopmental disorder associated with subtle abnormal cortical thickness and cortical surface area. However, it is unclear whether these abnormalities exist in neonates associated with genetic risk for schizophrenia. To this end, this preliminary study was conducted to identify possible abnormalities of cortical thickness and surface area in the high-genetic-risk neonates. Structural magnetic resonance images were acquired from offspring of mothers (N = 21) who had schizophrenia (N = 12) or schizoaffective disorder (N = 9), and also matched healthy neonates of mothers who were free of psychiatric illness (N = 26). Neonatal cortical surfaces were reconstructed and parcellated as regions of interest (ROIs), and cortical thickness for each vertex was computed as the shortest distance between the inner and outer surfaces. Comparisons were made for the average cortical thickness and total surface area in each of 68 cortical ROIs. After false discovery rate (FDR) correction, it was found that the female high-genetic-risk neonates had significantly thinner cortical thickness in the right lateral occipital cortex than the female control neonates. Before FDR correction, the high-genetic-risk neonates had significantly thinner cortex in the left transverse temporal gyrus, left banks of superior temporal sulcus, left lingual gyrus, right paracentral cortex, right posterior cingulate cortex, right temporal pole, and right lateral occipital cortex, compared with the control neonates. Before FDR correction, in comparison with control neonates, male high-risk neonates had significantly thicker cortex in the left frontal pole, left cuneus cortex, and left lateral occipital cortex; while female high-risk neonates had significantly thinner cortex in the bilateral paracentral, bilateral lateral occipital, left transverse temporal, left pars opercularis, right cuneus, and right posterior cingulate cortices. The high-risk neonates also had significantly smaller

  18. Cortical thickness and surface area in neonates at high risk for schizophrenia.

    PubMed

    Li, Gang; Wang, Li; Shi, Feng; Lyall, Amanda E; Ahn, Mihye; Peng, Ziwen; Zhu, Hongtu; Lin, Weili; Gilmore, John H; Shen, Dinggang

    2016-01-01

    Schizophrenia is a neurodevelopmental disorder associated with subtle abnormal cortical thickness and cortical surface area. However, it is unclear whether these abnormalities exist in neonates associated with genetic risk for schizophrenia. To this end, this preliminary study was conducted to identify possible abnormalities of cortical thickness and surface area in the high-genetic-risk neonates. Structural magnetic resonance images were acquired from offspring of mothers (N = 21) who had schizophrenia (N = 12) or schizoaffective disorder (N = 9), and also matched healthy neonates of mothers who were free of psychiatric illness (N = 26). Neonatal cortical surfaces were reconstructed and parcellated as regions of interest (ROIs), and cortical thickness for each vertex was computed as the shortest distance between the inner and outer surfaces. Comparisons were made for the average cortical thickness and total surface area in each of 68 cortical ROIs. After false discovery rate (FDR) correction, it was found that the female high-genetic-risk neonates had significantly thinner cortical thickness in the right lateral occipital cortex than the female control neonates. Before FDR correction, the high-genetic-risk neonates had significantly thinner cortex in the left transverse temporal gyrus, left banks of superior temporal sulcus, left lingual gyrus, right paracentral cortex, right posterior cingulate cortex, right temporal pole, and right lateral occipital cortex, compared with the control neonates. Before FDR correction, in comparison with control neonates, male high-risk neonates had significantly thicker cortex in the left frontal pole, left cuneus cortex, and left lateral occipital cortex; while female high-risk neonates had significantly thinner cortex in the bilateral paracentral, bilateral lateral occipital, left transverse temporal, left pars opercularis, right cuneus, and right posterior cingulate cortices. The high-risk neonates also had significantly

  19. Experimental analysis of high oxygen concentration influences on horizontal flame spread over PA6 and epoxy

    NASA Astrophysics Data System (ADS)

    Wei, Ruichao; Yuen, Richard; Wang, Jian

    2017-05-01

    The combustion characteristic of material in high oxygen concentration is directly related to the safety of elevated oxygen environment similar to oxygen bombs and future spacecraft. In this study, flame front and flame spread rate in high oxygen concentration are discussed. Thermoplastic material polyamide (PA6) and thermosetting material epoxy are selected as comparison material. The variation of flame front over epoxy is more stable than PA6 which has dripping phenomenon during the flame spread process. The flame spread rate of both PA6 and epoxy have a power law with the increasing oxygen concentration.

  20. Alpha-Tocopherol Counteracts the Effect of Ethanol on Cortical Spreading Depression in Rats of Various Ages, With and Without Ethanol Abstinence.

    PubMed

    Abadie-Guedes, Ricardo; Bezerra, Ranilson de Souza; Guedes, Rubem Carlos Araújo

    2016-04-01

    We previously demonstrated that acute and chronic treatment with ethanol (EtOH), respectively, decelerated and accelerated the propagation of cortical spreading depression (CSD) in rats and that the antioxidant carotenoid astaxanthin counteracted these effects. Here, we investigated whether noncarotenoid antioxidants exert the same action by testing α-tocopherol in rats of various ages, with and without 5 to 10 days of EtOH abstinence. Male Wistar young adult (60 to 80 days old) and mature adult (150 to 180 days old) rats received per gavage acute (1 day) or chronic (21 days) treatment with 3 g/kg/d EtOH combined with acute (300 mg/kg) or chronic (85 mg/kg/d) treatment with α-tocopherol or vehicle-only treatment (olive oil and water for α-tocopherol and EtOH, respectively). CSD was recorded over 4 hours and the velocity of CSD propagation was calculated. On both ages, animals under chronic EtOH treatment were subjected to CSD recording immediately after EtOH treatment or after a 5- to 10-day period of EtOH abstinence. In both age groups, acute and chronic EtOH exposure decelerated and accelerated CSD, respectively, versus the corresponding control groups. Addition of α-tocopherol counteracted the effects of EtOH on CSD, returning CSD velocities to levels in control groups (p < 0.05). Chronic α-tocopherol (85 mg/kg/d) did not alter CSD. Our data reinforce the counteracting role of antioxidants on brain processes involved in the action of EtOH on CSD and suggest that this role is not a particular property of carotenoids; furthermore, this general feature of antioxidants is not substantially influenced by age or by 5 to 10 days of EtOH abstinence. Copyright © 2016 by the Research Society on Alcoholism.

  1. Neonatal taurine and alanine modulate anxiety-like behavior and decelerate cortical spreading depression in rats previously suckled under different litter sizes.

    PubMed

    Francisco, Elian da Silva; Guedes, Rubem Carlos Araújo

    2015-11-01

    The amino acids taurine and alanine play a role in several physiological processes, including behavior and the electrical activity of the brain. In this study, we investigated the effect of treatment with taurine or alanine on anxiety-like behavior and the excitability-dependent phenomenon known as cortical spreading depression (CSD), using rats suckled in litters with 9 and 15 pups (groups L9 and L15). From postnatal days 7 to 27, the animals received per gavage 300 mg/kg/day of taurine or alanine or both. At 28 days, we tested the animals in the elevated plus maze, and at 33-35 days, we recorded CSD and analyzed its velocity of propagation, amplitude, and duration. Compared with water-treated controls, the L9 groups treated with taurine or alanine displayed anxiolytic behavior (higher number of entries in the open arms; p < 0.05), and reduced CSD velocity (p < 0.001). The effect of both amino acids on CSD was also found in the L15 groups and in five additional L9 groups (naïve, water, taurine, alanine, or both) treated at adulthood (90-110 days). The L15 condition resulted in smaller durations and higher CSD velocities compared with the L9 condition. Besides reinforcing previous evidence of behavioral modulation by taurine and alanine, our data are the first confirmation that treatment with these amino acids decelerates CSD regardless of lactation conditions (normal versus unfavorable lactation) or age at amino acid administration (young versus adult). The results suggest a modulating role for both amino acids on anxiety behavior and neuronal electrical activity.

  2. High-expanding cortical regions in human development and evolution are related to higher intellectual abilities.

    PubMed

    Fjell, Anders M; Westlye, Lars T; Amlien, Inge; Tamnes, Christian K; Grydeland, Håkon; Engvig, Andreas; Espeseth, Thomas; Reinvang, Ivar; Lundervold, Astri J; Lundervold, Arvid; Walhovd, Kristine B

    2015-01-01

    Cortical surface area has tremendously expanded during human evolution, and similar patterns of cortical expansion have been observed during childhood development. An intriguing hypothesis is that the high-expanding cortical regions also show the strongest correlations with intellectual function in humans. However, we do not know how the regional distribution of correlations between intellectual function and cortical area maps onto expansion in development and evolution. Here, in a sample of 1048 participants, we show that regions in which cortical area correlates with visuospatial reasoning abilities are generally high expanding in both development and evolution. Several regions in the frontal cortex, especially the anterior cingulate, showed high expansion in both development and evolution. The area of these regions was related to intellectual functions in humans. Low-expanding areas were not related to cognitive scores. These findings suggest that cortical regions involved in higher intellectual functions have expanded the most during development and evolution. The radial unit hypothesis provides a common framework for interpretation of the findings in the context of evolution and prenatal development, while additional cellular mechanisms, such as synaptogenesis, gliogenesis, dendritic arborization, and intracortical myelination, likely impact area expansion in later childhood.

  3. Retrieval of high-fidelity memory arises from distributed cortical networks.

    PubMed

    Wais, Peter E; Jahanikia, Sahar; Steiner, Daniel; Stark, Craig E L; Gazzaley, Adam

    2017-04-01

    Medial temporal lobe (MTL) function is well established as necessary for memory of facts and events. It is likely that lateral cortical regions critically guide cognitive control processes to tune in high-fidelity details that are most relevant for memory retrieval. Here, convergent results from functional and structural MRI show that retrieval of detailed episodic memory arises from lateral cortical-MTL networks, including regions of inferior frontal and angular gyrii. Results also suggest that recognition of items based on low-fidelity, generalized information, rather than memory arising from retrieval of relevant episodic details, is not associated with functional connectivity between MTL and lateral cortical regions. Additionally, individual differences in microstructural properties in white matter pathways, associated with distributed MTL-cortical networks, are positively correlated with better performance on a mnemonic discrimination task.

  4. The effect of high voltage, high frequency pulsed electric field on slain ovine cortical bone.

    PubMed

    Asgarifar, Hajarossadat; Oloyede, Adekunle; Zare, Firuz

    2014-04-01

    High power, high frequency pulsed electric fields known as pulsed power (PP) has been applied recently in biology and medicine. However, little attention has been paid to investigate the application of pulse power in musculoskeletal system and its possible effect on functional behavior and biomechanical properties of bone tissue. This paper presents the first research investigating whether or not PP can be applied safely on bone tissue as a stimuli and what will be the possible effect of these signals on the characteristics of cortical bone by comparing the mechanical properties of this type of bone pre and post expose to PP and in comparison with the control samples. A positive buck-boost converter was applied to generate adjustable high voltage, high frequency pulses (up to 500 V and 10 kHz). The functional behavior of bone in response to pulse power excitation was elucidated by applying compressive loading until failure. The stiffness, failure stress (strength) and the total fracture energy (bone toughness) were determined as a measure of the main bone characteristics. Furthermore, an ultrasonic technique was applied to determine and comprise bone elasticity before and after pulse power stimulation. The elastic property of cortical bone samples appeared to remain unchanged following exposure to pulse power excitation for all three orthogonal directions obtained from ultrasonic technique and similarly from the compression test. Nevertheless, the compressive strength and toughness of bone samples were increased when they were exposed to 66 h of high power pulsed electromagnetic field compared to the control samples. As the toughness and the strength of the cortical bone tissue are directly associated with the quality and integrity of the collagen matrix whereas its stiffness is primarily related to bone mineral content these overall results may address that although, the pulse power stimulation can influence the arrangement or the quality of the collagen network

  5. Effective Suppression of Pathological Synchronization in Cortical Networks by Highly Heterogeneous Distribution of Inhibitory Connections

    PubMed Central

    Kada, Hisashi; Teramae, Jun-Nosuke; Tokuda, Isao T.

    2016-01-01

    Even without external random input, cortical networks in vivo sustain asynchronous irregular firing with low firing rate. In addition to detailed balance between excitatory and inhibitory activities, recent theoretical studies have revealed that another feature commonly observed in cortical networks, i.e., long-tailed distribution of excitatory synapses implying coexistence of many weak and a few extremely strong excitatory synapses, plays an essential role in realizing the self-sustained activity in recurrent networks of biologically plausible spiking neurons. The previous studies, however, have not considered highly non-random features of the synaptic connectivity, namely, bidirectional connections between cortical neurons are more common than expected by chance and strengths of synapses are positively correlated between pre- and postsynaptic neurons. The positive correlation of synaptic connections may destabilize asynchronous activity of networks with the long-tailed synaptic distribution and induce pathological synchronized firing among neurons. It remains unclear how the cortical network avoids such pathological synchronization. Here, we demonstrate that introduction of the correlated connections indeed gives rise to synchronized firings in a cortical network model with the long-tailed distribution. By using a simplified feed-forward network model of spiking neurons, we clarify the underlying mechanism of the synchronization. We then show that the synchronization can be efficiently suppressed by highly heterogeneous distribution, typically a lognormal distribution, of inhibitory-to-excitatory connection strengths in a recurrent network model of cortical neurons. PMID:27803659

  6. Spread of academic success in a high school social network.

    PubMed

    Blansky, Deanna; Kavanaugh, Christina; Boothroyd, Cara; Benson, Brianna; Gallagher, Julie; Endress, John; Sayama, Hiroki

    2013-01-01

    Application of social network analysis to education has revealed how social network positions of K-12 students correlate with their behavior and academic achievements. However, no study has been conducted on how their social network influences their academic progress over time. Here we investigated correlations between high school students' academic progress over one year and the social environment that surrounds them in their friendship network. We found that students whose friends' average GPA (Grade Point Average) was greater (or less) than their own had a higher tendency toward increasing (or decreasing) their academic ranking over time, indicating social contagion of academic success taking place in their social network.

  7. High frequency oscillations mirror disease activity in patients with focal cortical dysplasia.

    PubMed

    Kerber, Karolin; LeVan, Pierre; Dümpelmann, Matthias; Fauser, Susanne; Korinthenberg, Rudolf; Schulze-Bonhage, Andreas; Jacobs, Julia

    2013-08-01

    The study analyzes the occurrence of high frequency oscillations in different types of focal cortical dysplasia in 22 patients with refractory epilepsy. High frequency oscillations are biomarkers for epileptic tissue, but it is unknown whether they can reflect increasingly dysplastic tissue changes as well as epileptic disease activity. High frequency oscillations (80-450 Hz) were visually marked by two independent reviewers in all channels of intracranial implanted grid, strips, and depth electrodes in patients with focal cortical dysplasia and refractory epilepsy. Rates of high frequency oscillations in patients with pathologically confirmed focal cortical dysplasia of Palmini type 1a and b were compared with those in type 2a and b. Patients with focal cortical dysplasia type 2 had significantly more seizures than those with type 1 (p < 0.001). Rates of high frequency oscillations were significantly higher in patients with focal cortical dysplasia type 2 versus type 1 (p < 0.001). In addition, it could be confirmed that rates of high frequency oscillations were significantly higher in presumed epileptogenic areas than outside (p < 0.001). Activity of high frequency oscillations mirrors the higher epileptogenicity of focal cortical dysplasia type 2 lesions compared to type 1 lesions. Therefore, rates of high frequency oscillations can reflect disease activity of a lesion. This has implications for the use of high frequency oscillations as biomarkers for epileptogenic areas, because a detailed analysis of their rates may be necessary to use high frequency oscillations as a predictive tool in epilepsy surgery. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  8. Meta-cognition is associated with cortical thickness in youth at clinical high risk of psychosis.

    PubMed

    Buchy, Lisa; Stowkowy, Jacque; MacMaster, Frank P; Nyman, Karissa; Addington, Jean

    2015-09-30

    Meta-cognition is compromised in people with schizophrenia and people at clinical high risk (CHR) of psychosis. In the current work in a CHR sample, we hypothesized that meta-cognitive functions would correlate with cortical thickness in five brain regions implicated in the pathogenesis of psychosis: inferior and middle frontal cortices, anterior cingulate cortex, superior temporal cortex and insula. Secondly, we hypothesized that similar neural systems would underlie different meta-cognitive functions. Narratives were gathered for 29 youth at CHR of psychosis using a semi-structured interview. Four meta-cognitive functions within the narratives were measured with the Meta-cognition Assessment Scale and regressed on cortical thickness from our a priori regions of interest using FreeSurfer. Mapping statistics from our a priori regions of interest revealed that meta-cognition functions were associated with cortical thickness in inferior and middle frontal gyri, superior temporal cortex and insula. The distribution of cortical thickness was partially similar across the four MAS items. Results confirm our hypothesis that cortical thickness is significantly associated with meta-cognition in brain regions that consistently show gray matter reductions across the schizophrenia spectrum. Evidence for thickness covariation in a variety of regions suggests partial dependence in the neural architecture underlying various meta-cognitive functions in CHR.

  9. A method for isolating high quality RNA from mouse cortical and cancellous bone.

    PubMed

    Kelly, Natalie H; Schimenti, John C; Patrick Ross, F; van der Meulen, Marjolein C H

    2014-11-01

    The high incidence of fragility fractures in cortico-cancellous bone locations, plus the fact that individual skeletal sites exhibit different responsiveness to load and disease, emphasizes the need to document separately gene expression in cortical and cancellous bone. A further confounding factor is marrow contamination since its high cellularity may effect gene expression measurements. We isolated RNA from cortical and cancellous bone of intact mouse tibiae, and also after marrow removal by flushing or centrifugation. RNA isolated from cancellous bone by each method was sufficient for gene expression analysis. Centrifugation removed contaminating cells more efficiently than flushing, as indexed by histology and decreased expression of Icam4, a highly expressed erythroid gene. In contrast, centrifuged cortical bone had 12- and 13- fold higher expression of the bone-related genes Col1a1 and Bglap, while levels in marrow-free cancellous bone were 30- and 31-fold higher when compared to bone where marrow was left intact. Furthermore, cortical bone had higher expression of Col1a1 and Bglap than cancellous bone. Thus, RNA isolated by this novel approach can reveal site-specific changes in gene expression in cortical and cancellous bone sites.

  10. Linking contemporary high resolution magnetic resonance imaging to the von Economo legacy: A study on the comparison of MRI cortical thickness and histological measurements of cortical structure.

    PubMed

    Scholtens, Lianne H; de Reus, Marcel A; van den Heuvel, Martijn P

    2015-08-01

    The cerebral cortex is a distinctive part of the mammalian nervous system, displaying a spatial variety in cyto-, chemico-, and myelinoarchitecture. As part of a rich history of histological findings, pioneering anatomists von Economo and Koskinas provided detailed mappings on the cellular structure of the human cortex, reporting on quantitative aspects of cytoarchitecture of cortical areas. Current day investigations into the structure of human cortex have embraced technological advances in Magnetic Resonance Imaging (MRI) to assess macroscale thickness and organization of the cortical mantle in vivo. However, direct comparisons between current day MRI estimates and the quantitative measurements of early anatomists have been limited. Here, we report on a simple, but nevertheless important cross-analysis between the histological reports of von Economo and Koskinas on variation in thickness of the cortical mantle and MRI derived measurements of cortical thickness. We translated the von Economo cortical atlas to a subdivision of the commonly used Desikan-Killiany atlas (as part of the FreeSurfer Software package and a commonly used parcellation atlas in studies examining MRI cortical thickness). Next, values of "width of the cortical mantle" as provided by the measurements of von Economo and Koskinas were correlated to cortical thickness measurements derived from high-resolution anatomical MRI T1 data of 200+ subjects of the Human Connectome Project (HCP). Cross-correlation revealed a significant association between group-averaged MRI measurements of cortical thickness and histological recordings (r = 0.54, P < 0.001). Further validating such a correlation, we manually segmented the von Economo parcellation atlas on the standardized Colin27 brain dataset and applied the obtained three-dimensional von Economo segmentation atlas to the T1 data of each of the HCP subjects. Highly consistent with our findings for the mapping to the Desikan-Killiany regions, cross

  11. Slow dynamics and high variability in balanced cortical networks with clustered connections.

    PubMed

    Litwin-Kumar, Ashok; Doiron, Brent

    2012-11-01

    Anatomical studies demonstrate that excitatory connections in cortex are not uniformly distributed across a network but instead exhibit clustering into groups of highly connected neurons. The implications of clustering for cortical activity are unclear. We studied the effect of clustered excitatory connections on the dynamics of neuronal networks that exhibited high spike time variability owing to a balance between excitation and inhibition. Even modest clustering substantially changed the behavior of these networks, introducing slow dynamics during which clusters of neurons transiently increased or decreased their firing rate. Consequently, neurons exhibited both fast spiking variability and slow firing rate fluctuations. A simplified model shows how stimuli bias networks toward particular activity states, thereby reducing firing rate variability as observed experimentally in many cortical areas. Our model thus relates cortical architecture to the reported variability in spontaneous and evoked spiking activity.

  12. In vivo high-resolution 7 Tesla MRI shows early and diffuse cortical alterations in CADASIL.

    PubMed

    De Guio, François; Reyes, Sonia; Vignaud, Alexandre; Duering, Marco; Ropele, Stefan; Duchesnay, Edouard; Chabriat, Hugues; Jouvent, Eric

    2014-01-01

    Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin's scale ≤1 and Mini Mental State Examination (MMSE) ≥24). Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined.

  13. High-Resolution Cortical Dipole Imaging Using Spatial Inverse Filter Based on Filtering Property

    PubMed Central

    2016-01-01

    Cortical dipole imaging has been developed to visualize brain electrical activity in high spatial resolution. It is necessary to solve an inverse problem to estimate the cortical dipole distribution from the scalp potentials. In the present study, the accuracy of cortical dipole imaging was improved by focusing on filtering property of the spatial inverse filter. We proposed an inverse filter that optimizes filtering property using a sigmoid function. The ability of the proposed method was compared with the traditional inverse techniques, such as Tikhonov regularization, truncated singular value decomposition (TSVD), and truncated total least squares (TTLS), in a computer simulation. The proposed method was applied to human experimental data of visual evoked potentials. As a result, the estimation accuracy was improved and the localized dipole distribution was obtained with less noise. PMID:27688747

  14. Probing region-specific microstructure of human cortical areas using high angular and spatial resolution diffusion MRI.

    PubMed

    Aggarwal, Manisha; Nauen, David W; Troncoso, Juan C; Mori, Susumu

    2015-01-15

    Regional heterogeneity in cortical cyto- and myeloarchitecture forms the structural basis of mapping of cortical areas in the human brain. In this study, we investigate the potential of diffusion MRI to probe the microstructure of cortical gray matter and its region-specific heterogeneity across cortical areas in the fixed human brain. High angular resolution diffusion imaging (HARDI) data at an isotropic resolution of 92-μm and 30 diffusion-encoding directions were acquired using a 3D diffusion-weighted gradient-and-spin-echo sequence, from prefrontal (Brodmann area 9), primary motor (area 4), primary somatosensory (area 3b), and primary visual (area 17) cortical specimens (n=3 each) from three human subjects. Further, the diffusion MR findings in these cortical areas were compared with histological silver impregnation of the same specimens, in order to investigate the underlying architectonic features that constitute the microstructural basis of diffusion-driven contrasts in cortical gray matter. Our data reveal distinct and region-specific diffusion MR contrasts across the studied areas, allowing delineation of intracortical bands of tangential fibers in specific layers-layer I, layer VI, and the inner and outer bands of Baillarger. The findings of this work demonstrate unique sensitivity of diffusion MRI to differentiate region-specific cortical microstructure in the human brain, and will be useful for myeloarchitectonic mapping of cortical areas as well as to achieve an understanding of the basis of diffusion NMR contrasts in cortical gray matter. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Alterations in cortical thickness development in preterm-born individuals: Implications for high-order cognitive functions

    PubMed Central

    Nam, Kie Woo; Castellanos, Nazareth; Simmons, Andrew; Froudist-Walsh, Seán; Allin, Matthew P.; Walshe, Muriel; Murray, Robin M.; Evans, Alan; Muehlboeck, J-Sebastian; Nosarti, Chiara

    2015-01-01

    Very preterm birth (gestational age < 33 weeks) is associated with alterations in cortical thickness and with neuropsychological/behavioural impairments. Here we studied cortical thickness in very preterm born individuals and controls in mid-adolescence (mean age 15 years) and beginning of adulthood (mean age 20 years), as well as longitudinal changes between the two time points. Using univariate approaches, we showed both increases and decreases in cortical thickness in very preterm born individuals compared to controls. Specifically (1) very preterm born adolescents displayed extensive areas of greater cortical thickness, especially in occipitotemporal and prefrontal cortices, differences which decreased substantially by early adulthood; (2) at both time points, very preterm-born participants showed smaller cortical thickness, especially in parahippocampal and insular regions. We then employed a multivariate approach (support vector machine) to study spatially discriminating features between the two groups, which achieved a mean accuracy of 86.5%. The spatially distributed regions in which cortical thickness best discriminated between the groups (top 5%) included temporal, occipitotemporal, parietal and prefrontal cortices. Within these spatially distributed regions (top 1%), longitudinal changes in cortical thickness in left temporal pole, right occipitotemporal gyrus and left superior parietal lobe were significantly associated with scores on language-based tests of executive function. These results describe alterations in cortical thickness development in preterm-born individuals in their second decade of life, with implications for high-order cognitive processing. PMID:25871628

  16. Alterations of cortical pyramidal neurons in mice lacking high-affinity nicotinic receptors

    PubMed Central

    Ballesteros-Yáñez, Inmaculada; Benavides-Piccione, Ruth; Bourgeois, Jean-Pierre; Changeux, Jean-Pierre; DeFelipe, Javier

    2010-01-01

    The neuronal nicotinic acetylcholine receptors (nAChRs) are allosteric membrane proteins involved in multiple cognitive processes, including attention, learning, and memory. The most abundant form of heterooligomeric nAChRs in the brain contains the β2- and α4- subunits and binds nicotinic agonists with high affinity. In the present study, we investigated in the mouse the consequences of the deletion of one of the nAChR components: the β2-subunit (β2−/−) on the microanatomy of cortical pyramidal cells. Using an intracellular injection method, complete basal dendritic arbors of 650 layer III pyramidal neurons were sampled from seven cortical fields, including primary sensory, motor, and associational areas, in both β2−/− and WT animals. We observed that the pyramidal cell phenotype shows significant quantitative differences among different cortical areas in mutant and WT mice. In WT mice, the density of dendritic spines was rather similar in all cortical fields, except in the prelimbic/infralimbic cortex, where it was significantly higher. In the absence of the β2-subunit, the most significant reduction in the density of spines took place in this high-order associational field. Our data suggest that the β2-subunit is involved in the dendritic morphogenesis of pyramidal neurons and, in particular, in the circuits that contribute to the high-order functional connectivity of the cerebral cortex. PMID:20534523

  17. High-spatial-resolution mapping of the oxygen concentration in cortical tissue (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jaswal, Rajeshwer S.; Yaseen, Mohammad A.; Fu, Buyin; Boas, David A.; Sakadžic, Sava

    2016-03-01

    Due to a lack of imaging tools for high-resolution imaging of cortical tissue oxygenation, the detailed maps of the oxygen partial pressure (PO2) around arterioles, venules, and capillaries remain largely unknown. Therefore, we have limited knowledge about the mechanisms that secure sufficient oxygen delivery in microvascular domains during brain activation, and provide some metabolic reserve capacity in diseases that affect either microvascular networks or the regulation of cerebral blood flow (CBF). To address this challenge, we applied a Two-Photon PO2 Microscopy to map PO2 at different depths in mice cortices. Measurements were performed through the cranial window in the anesthetized healthy mice as well as in the mouse models of microvascular dysfunctions. In addition, microvascular morphology was recorded by the two-photon microscopy at the end of each experiment and subsequently segmented. Co-registration of the PO2 measurements and exact microvascular morphology enabled quantification of the tissue PO2 dependence on distance from the arterioles, capillaries, and venules at various depths. Our measurements reveal significant spatial heterogeneity of the cortical tissue PO2 distribution that is dominated by the high oxygenation in periarteriolar spaces. In cases of impaired oxygen delivery due to microvascular dysfunction, significant reduction in tissue oxygenation away from the arterioles was observed. These tissue domains may be the initial sites of cortical injury that can further exacerbate the progression of the disease.

  18. Risk Maps for the Spread of Highly Pathogenic Avian Influenza in Poultry

    PubMed Central

    Boender, Gert Jan; Hagenaars, Thomas J; Bouma, Annemarie; Nodelijk, Gonnie; Elbers, Armin R. W; de Jong, Mart C. M; van Boven, Michiel

    2007-01-01

    Devastating epidemics of highly contagious animal diseases such as avian influenza, classical swine fever, and foot-and-mouth disease underline the need for improved understanding of the factors promoting the spread of these pathogens. Here the authors present a spatial analysis of the between-farm transmission of a highly pathogenic H7N7 avian influenza virus that caused a large epidemic in The Netherlands in 2003. The authors developed a method to estimate key parameters determining the spread of highly transmissible animal diseases between farms based on outbreak data. The method allows for the identification of high-risk areas for propagating spread in an epidemiologically underpinned manner. A central concept is the transmission kernel, which determines the probability of pathogen transmission from infected to uninfected farms as a function of interfarm distance. The authors show how an estimate of the transmission kernel naturally provides estimates of the critical farm density and local reproduction numbers, which allows one to evaluate the effectiveness of control strategies. For avian influenza, the analyses show that there are two poultry-dense areas in The Netherlands where epidemic spread is possible, and in which local control measures are unlikely to be able to halt an unfolding epidemic. In these regions an epidemic can only be brought to an end by the depletion of susceptible farms by infection or massive culling. The analyses provide an estimate of the spatial range over which highly pathogenic avian influenza viruses spread between farms, and emphasize that control measures aimed at controlling such outbreaks need to take into account the local density of farms. PMID:17447838

  19. Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex

    PubMed Central

    Major, Sebastian; Pannek, Heinz-Wolfgang; Woitzik, Johannes; Scheel, Michael; Wiesenthal, Dirk; Martus, Peter; Winkler, Maren K.L.; Hartings, Jed A.; Fabricius, Martin; Speckmann, Erwin-Josef; Gorji, Ali

    2012-01-01

    Spreading depolarization of cells in cerebral grey matter is characterized by massive ion translocation, neuronal swelling and large changes in direct current-coupled voltage recording. The near-complete sustained depolarization above the inactivation threshold for action potential generating channels initiates spreading depression of brain activity. In contrast, epileptic seizures show modest ion translocation and sustained depolarization below the inactivation threshold for action potential generating channels. Such modest sustained depolarization allows synchronous, highly frequent neuronal firing; ictal epileptic field potentials being its electrocorticographic and epileptic seizure its clinical correlate. Nevertheless, Leão in 1944 and Van Harreveld and Stamm in 1953 described in animals that silencing of brain activity induced by spreading depolarization changed during minimal electrical stimulations. Eventually, epileptic field potentials were recorded during the period that had originally seen spreading depression of activity. Such spreading convulsions are characterized by epileptic field potentials on the final shoulder of the large slow potential change of spreading depolarization. We here report on such spreading convulsions in monopolar subdural recordings in 2 of 25 consecutive aneurismal subarachnoid haemorrhage patients in vivo and neocortical slices from 12 patients with intractable temporal lobe epilepsy in vitro. The in vitro results suggest that γ-aminobutyric acid-mediated inhibition protects from spreading convulsions. Moreover, we describe arterial pulse artefacts mimicking epileptic field potentials in three patients with subarachnoid haemorrhage that ride on the slow potential peak. Twenty-one of the 25 subarachnoid haemorrhage patients (84%) had 656 spreading depolarizations in contrast to only three patients (12%) with 55 ictal epileptic events isolated from spreading depolarizations. Spreading depolarization frequency and depression

  20. Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activity.

    PubMed

    Riès, Stephanie K; Dhillon, Rummit K; Clarke, Alex; King-Stephens, David; Laxer, Kenneth D; Weber, Peter B; Kuperman, Rachel A; Auguste, Kurtis I; Brunner, Peter; Schalk, Gerwin; Lin, Jack J; Parvizi, Josef; Crone, Nathan E; Dronkers, Nina F; Knight, Robert T

    2017-06-06

    Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70-150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain.

  1. Cosputtered composition-spread reproducibility established by high-throughput x-ray fluorescence

    SciTech Connect

    Gregoire, John M.; Dale, Darren; Kazimirov, Alexander; DiSalvo, Francis J.; Dover, R. Bruce van

    2010-09-15

    We describe the characterization of sputtered yttria-zirconia composition spread thin films by x-ray fluorescence (XRF). We also discuss our automated analysis of the XRF data, which was collected in a high throughput experiment at the Cornell High Energy Synchrotron Source. The results indicate that both the composition reproducibility of the library deposition and the composition measurements have a precision of better than 1 atomic percent.

  2. Medial open wedge high tibial osteotomy: the effect of the cortical hinge on posterior tibial slope.

    PubMed

    Wang, Joon Ho; Bae, Ji Hoon; Lim, Hong Chul; Shon, Won Yong; Kim, Cheol Woong; Cho, Jae Woo

    2009-12-01

    High tibial osteotomy can affect the posterior tibial slope in the sagittal plane because of the triangular configuration of the proximal tibia. However, the effect of the location of cortical hinge on posterior tibial slope has not been previously described. Posterolateral location of the cortical hinge will increase posterior tibial slope after medial open wedge osteotomy, and lateral location of the cortical hinge will not affect the change of the posterior tibial slope. Controlled laboratory study. We performed incomplete valgus open wedge osteotomy on 12 paired knees of 6 fresh-frozen human cadavers (age, 63.4 + or - 7.5 years) using an OrthoPilot navigation system. The left and right legs of each specimen were randomly assigned to a posterolateral (group A) or a lateral (group B) cortical hinge group. Changes in mean medial proximal tibial angle, posterior tibial slope, and opening wedge angle were measured and compared after surgery. In group A, mean medial proximal tibial angle changed from 84.37 degrees + or - 2.8 degrees to 93.48 degrees + or - 3.06 degrees (P = .028); mean posterior tibial slope increased significantly from 8.71 degrees + or - 0.81 degrees to 12.16 degrees + or - 0.84 degrees (P = .031); and mean wedge angle was 1.92 degrees + or - 0.46 degrees . In group B, mean medial proximal tibial angle changed from 82.98 degrees + or - 2.53 degrees to 90.89 degrees + or - 3.25 degrees (P = .027); mean posterior tibial slope changed from 9.19 degrees + or - 1.11 degrees to 9.78 degrees + or - 1.27 degrees (P = .029); and mean wedge angle was 7.25 degrees + or - 0.72 degrees . The location of the intact cortical hinge affects the posterior tibia slope. During medial open wedge osteotomy, the change of posterior tibial slope was larger in the posterolateral than in the lateral cortical hinge group. To prevent the unintentional increase of the posterior tibial slope, special attention should be paid to locate the intact cortical hinge on the lateral

  3. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer

    PubMed Central

    Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G.; Meier, Samuel M.; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar

    2016-01-01

    The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors. PMID:27665539

  4. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer.

    PubMed

    Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G; Meier, Samuel M; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar

    2016-09-20

    The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors.

  5. In Vivo High-Resolution 7 Tesla MRI Shows Early and Diffuse Cortical Alterations in CADASIL

    PubMed Central

    De Guio, François; Reyes, Sonia; Vignaud, Alexandre; Duering, Marco; Ropele, Stefan; Duchesnay, Edouard; Chabriat, Hugues; Jouvent, Eric

    2014-01-01

    Background and Purpose Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin’s scale ≤1 and Mini Mental State Examination (MMSE) ≥24). Methods Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. Results MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. Conclusions Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined. PMID:25165824

  6. Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread

    PubMed Central

    Bachmayr-Heyda, Anna; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Deycmar, Simon; Reiner, Agnes T.; Polterauer, Stephan; Dekan, Sabine; Pils, Dietmar

    2016-01-01

    High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread types in HGSOC apparent during surgery: miliary (numerous millet-sized implants) and non-miliary (few big, bulky implants). The former one is defined by a more epithelial-like tumor cell characteristic with less immune cell reactivity and with significant worse prognosis, even if corrected for typical clinicopathologic factors. 23 HGSOC patients were enrolled in this study. Isolated tumor cells from fresh tumor tissues of ovarian and peritoneal origin and from ascites were used for ribosomal RNA depleted RNA and small RNA sequencing. RT-qPCR was used to validate results and an independent cohort of 32 patients to validate the impact on survival. Large and small RNA sequencing data were integrated and a new gene-miRNA set analysis method was developed. Thousands of new small RNAs (miRNAs and piwi-interacting RNAs) were predicted and a 13 small RNA signature was developed to predict spread type from formalin-fixed paraffin-embedded tissues. Furthermore, integrative analyses of RNA sequencing and small RNA sequencing data revealed a global upregulation of the competing endogenous RNA network in tumor tissues of non-miliary compared to miliary spread, i.e. higher expression of circular RNAs and long non-coding RNAs compared to coding RNAs but unchanged abundance of small RNAs. This global deregulated expression pattern could be co-responsible for the spread characteristic, miliary or non-miliary, in ovarian cancer. PMID:27172797

  7. High-frequency EEG covaries with spike burst patterns detected in cortical neurons

    PubMed Central

    Baker, Stuart N.; Herz, Andreas V. M.; Curio, Gabriel

    2011-01-01

    Invasive microelectrode recordings measure neuronal spikes, which are commonly considered inaccessible through standard surface electroencephalogram (EEG). Yet high-frequency EEG potentials (hf-EEG, f > 400 Hz) found in somatosensory evoked potentials of primates may reflect the mean population spike responses of coactivated cortical neurons. Since cortical responses to electrical nerve stimulation vary strongly from trial to trial, we investigated whether the hf-EEG signal can also echo single-trial variability observed at the single-unit level. We recorded extracellular single-unit activity in the primary somatosensory cortex of behaving macaque monkeys and identified variable spike burst responses following peripheral stimulation. Each of these responses was classified according to the timing of its spike constituents, conforming to one of a discrete set of spike patterns. We here show that these spike patterns are accompanied by variations in the concomitant epidural hf-EEG. These variations cannot be explained by fluctuating stimulus efficacy, suggesting that they were generated within the thalamocortical network. As high-frequency EEG signals can also be reliably recorded from the scalp of human subjects, they may provide a noninvasive window on fluctuating cortical spike activity in humans. PMID:21490283

  8. Exponential quantum spreading in a class of kicked rotor systems near high-order resonances

    NASA Astrophysics Data System (ADS)

    Wang, Hailong; Wang, Jiao; Guarneri, Italo; Casati, Giulio; Gong, Jiangbin

    2013-11-01

    Long-lasting exponential quantum spreading was recently found in a simple but very rich dynamical model, namely, an on-resonance double-kicked rotor model [J. Wang, I. Guarneri, G. Casati, and J. B. Gong, Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.107.234104 107, 234104 (2011)]. The underlying mechanism, unrelated to the chaotic motion in the classical limit but resting on quasi-integrable motion in a pseudoclassical limit, is identified for one special case. By presenting a detailed study of the same model, this work offers a framework to explain long-lasting exponential quantum spreading under much more general conditions. In particular, we adopt the so-called “spinor” representation to treat the kicked-rotor dynamics under high-order resonance conditions and then exploit the Born-Oppenheimer approximation to understand the dynamical evolution. It is found that the existence of a flat band (or an effectively flat band) is one important feature behind why and how the exponential dynamics emerges. It is also found that a quantitative prediction of the exponential spreading rate based on an interesting and simple pseudoclassical map may be inaccurate. In addition to general interests regarding the question of how exponential behavior in quantum systems may persist for a long time scale, our results should motivate further studies toward a better understanding of high-order resonance behavior in δ-kicked quantum systems.

  9. High spread of Schmallenberg virus among roe deer (Capreolus capreolus) in Spain.

    PubMed

    Díaz, José M; Prieto, Alberto; López, Ceferino; Díaz, Pablo; Pérez, Ana; Panadero, Rosario; Pajares, Gerardo; Díez-Baños, Pablo; Morrondo, Patrocinio; Fernández, Gonzalo

    2015-10-01

    Schmallenberg virus (SBV) is an emergent virus in northwestern Europe since 2011. We conducted this study to evaluate the spread of this virus in a wild ruminant community. During 2013 and 2014, 75 serum samples of roe deer were collected from different locations of the Spanish geography and analysed for the presence of antibodies. The results revealed a widespread exposure to SBV, as well as a high seroprevalence (53.3%, CI95% 42.16–64.18). These findings demand more research with regard to the impact of SBV on roe deer health and the interactions with livestock. Results also show this species as potentially suitable for monitoring the spread of the virus through sylvatic areas.

  10. Power and coherence of cortical High Frequency Oscillations during wakefulness and sleep.

    PubMed

    Cavelli, Matías; Rojas-Líbano, Daniel; Schwarzkopf, Natalia; Castro-Zaballa, Santiago; Gonzalez, Joaquín; Mondino, Alejandra; Santana, Noelia; Benedetto, Luciana; Falconi, Atilio; Torterolo, Pablo

    2017-09-18

    Recently, a novel type of fast cortical oscillatory activity that occurs between 110 and 160 Hz (high-frequency oscillations (HFO)) was described. HFO are modulated by the theta rhythm in hippocampus and neocortex during active wakefulness and REM sleep. Since theta-HFO coupling increases during REM, a role for HFO in memory consolidation has been proposed. However, global properties like the cortex-wide topographic distribution, and the cortico-cortical coherence remain unknown. In the present study, we recorded the electroencephalogram during sleep and wakefulness in the rat, and analyzed the spatial extent of the HFO band power and coherence. We confirmed that the HFO amplitude is phase-locked to theta oscillations and is modified by behavioral states. During active wakefulness, HFO power was relatively higher in the neocortex and olfactory bulb compared to sleep. HFO power decreased during non-REM and had an intermediate level during REM sleep. Furthermore, coherence was larger during active wakefulness than non-REM, while REM showed a complex pattern in which coherence increased only in intra and decrease in inter-hemispheric combination of electrodes. This coherence pattern is different from gamma (30-100 Hz) coherence, which is reduced during REM sleep. The present data show an important HFO cortico-cortical dialogue during active wakefulness even when the level of theta co-modulation is lower than in REM. In contrast, during REM, this dialogue is highly modulated by theta, and restricted to intra-hemispheric medial-posterior cortical regions. Further studies combining behavior, electrophysiology and new analytical tools are needed to plunge deeper into the functional significance of the HFO. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Highly siderophile element systematics of abyssal peridotites from intermediate and fast spreading ridges

    NASA Astrophysics Data System (ADS)

    Brown, D. B.; Day, J. M.; Waters, C. L.

    2016-12-01

    Abyssal peridotites are residues of both modern and ancient partial melt extraction at oceanic ridges and can be used to examine melting processes and mantle heterogeneity. The highly siderophile elements (HSE: Os, Ir, Ru, Pt, Pd, Re, and the 187Re-187Os system embedded within them), are useful for investigating these issues, as they are generally strongly compatible. To date, limited data on HSE and Os isotopes has been obtained on abyssal peridotites from fast spreading centers. Here, we report new HSE abundance and 187Os/188Os data for Pacific Antarctic Ridge (PAR) and East Pacific Rise (EPR) abyssal peridotites. Samples from the PAR were dredged from two separate localities along the Udintsev Fracture Zone, and EPR samples were taken from Hess Deep. The PAR full spreading rate ranges from 54-83mm/year [1,2] and is 75 mm/year [2] at the Udintsev Fracture Zone. These spreading rates characterize the PAR as an intermediate spreading ridge, whereas the fast spreading EPR has a full rate ranging from 128-157 mm/year [3]. The 187Os/188Os ratios for whole-rocks from the PAR range from 0.114 to 0.134, with Re depletion ages (TRD) varying from 1 Ga to present. Despite the large variation in 187Os/188Os, HSE patterns are primitive mantle-like [4], with Ru/Ir ratios ranging from 1.5-2.1. Depletions in Re and Pd are present, as is expected in partial melt residues, and the samples have undergone 4-15% partial melting based on the rare earth elements (REE). The EPR exhibits higher levels of melt depletion ranging from 18-24%. New results show Hess Deep samples have 187Os/188Os ratios of 0.123 and 0.125 for whole-rocks. These findings indicate that PAR and EPR Os isotopic data overlap with the global record of abyssal peridotites from slower ridges and that Os isotopic heterogeneities are preserved across a wide range of spreading rates and degrees of melt extraction. [1] Géli, L., et al. (1997), Science, 278, 1281-1284; [2] Castillo, P.R., et al. (1998) EPSL, 154

  12. Intramyocardial injection of hydrogel with high interstitial spread does not impact action potential propagation.

    PubMed

    Suarez, Sophia L; Rane, Aboli A; Muñoz, Adam; Wright, Adam T; Zhang, Shirley X; Braden, Rebecca L; Almutairi, Adah; McCulloch, Andrew D; Christman, Karen L

    2015-10-01

    Injectable biomaterials have been evaluated as potential new therapies for myocardial infarction (MI) and heart failure. These materials have improved left ventricular (LV) geometry and ejection fraction, yet there remain concerns that biomaterial injection may create a substrate for arrhythmia. Since studies of this risk are lacking, we utilized optical mapping to assess the effects of biomaterial injection and interstitial spread on cardiac electrophysiology. Healthy and infarcted rat hearts were injected with a model poly(ethylene glycol) hydrogel with varying degrees of interstitial spread. Activation maps demonstrated delayed propagation of action potentials across the LV epicardium in the hydrogel-injected group when compared to saline and no-injection groups. However, the degree of the electrophysiological changes depended on the spread characteristics of the hydrogel, such that hearts injected with highly spread hydrogels showed no conduction abnormalities. Conversely, the results of this study indicate that injection of a hydrogel exhibiting minimal interstitial spread may create a substrate for arrhythmia shortly after injection by causing LV activation delays and reducing gap junction density at the site of injection. Thus, this work establishes site of delivery and interstitial spread characteristics as important factors in the future design and use of biomaterial therapies for MI treatment. Biomaterials for treating myocardial infarction have become an increasingly popular area of research. Within the past few years, this work has transitioned to some large animals models, and Phase I & II clinical trials. While these materials have preserved/improved cardiac function the effect of these materials on arrhythmogenesis, which is of considerable concern when injecting anything into the heart, has yet to be understood. Our manuscript is therefore a first of its kind in that it directly examines the potential of an injectable material to create a substrate

  13. Highly nutrient-dense spreads: a new approach to delivering multiple micronutrients to high-risk groups.

    PubMed

    Briend, A

    2001-05-01

    Using a highly fortified food is the most attractive option to bringing missing nutrients to vulnerable groups. The recent development of a highly nutrient-dense spread (HNDS) for the treatment of malnourished children may have some relevance for other high-risk groups. Traditionally, severely malnourished children are fed for 3-4 weeks during their recovery with adapted milk feeds prepared by mixing dried skimmed milk, oil and sugar with a vitamin and mineral complex. This approach, however, is difficult to implement, since these feeds are excellent growth media for bacteria, and they must be prepared and fed under close supervision. This constraint led to the development of a HNDS, which is obtained by replacing part of the dried skimmed milk with a mixture of groundnut butter and powdered lactoserum. This spread can be eaten without dilution with water and preliminary trials showed that children preferred this HNDS to traditional liquid diets. In HNDS all powdered ingredients are embedded in fat which protects vitamins against oxidation and increases the shelf life of this product. Spreads also have a very low humidity and bacteria do not grow in it. Attempts to use spreads to supplement other vulnerable groups such as moderately malnourished children and pregnant women are discussed.

  14. Modelling the wind-borne spread of highly pathogenic avian influenza virus between farms.

    PubMed

    Ssematimba, Amos; Hagenaars, Thomas J; de Jong, Mart C M

    2012-01-01

    A quantitative understanding of the spread of contaminated farm dust between locations is a prerequisite for obtaining much-needed insight into one of the possible mechanisms of disease spread between farms. Here, we develop a model to calculate the quantity of contaminated farm-dust particles deposited at various locations downwind of a source farm and apply the model to assess the possible contribution of the wind-borne route to the transmission of Highly Pathogenic Avian Influenza virus (HPAI) during the 2003 epidemic in the Netherlands. The model is obtained from a Gaussian Plume Model by incorporating the dust deposition process, pathogen decay, and a model for the infection process on exposed farms. Using poultry- and avian influenza-specific parameter values we calculate the distance-dependent probability of between-farm transmission by this route. A comparison between the transmission risk pattern predicted by the model and the pattern observed during the 2003 epidemic reveals that the wind-borne route alone is insufficient to explain the observations although it could contribute substantially to the spread over short distance ranges, for example, explaining 24% of the transmission over distances up to 25 km.

  15. Effects of high vs. low cadence training on cyclists' brain cortical activity during exercise.

    PubMed

    Ludyga, Sebastian; Gronwald, Thomas; Hottenrott, Kuno

    2016-04-01

    As brain cortical activity depends on cadence, exercise at different pedaling frequencies could provide efficient stimuli for functional adaptations of the brain. Therefore, the purpose of the study was to investigate the effects of cadence-specific training on brain cortical activity as well as endurance performance. Randomized, controlled experimental trial in a repeated measure design. Male (n=24) and female (n=12) cyclists were randomly assigned to either a high cadence group (HCT), a low cadence group (LCT) or a control group (CON) for a 4 week intervention period. All groups performed 4h of basic endurance training per week. Additionally, HCT and LCT completed four cadence-specific 60min sessions weekly. At baseline and after 4 weeks subjects performed an incremental test with spirometry as well as an interval session (constant load; varying cadences) with continuous recording of electroencephalographic (EEG) rhythms. In contrast to CON, HCT and LCT elicited similar improvements of maximal oxygen uptake and power at the individual anaerobic threshold. Additionally, there was a reduction of alpha-, beta- and overall-power spectral density in HCT, which was more pronounced at high cadences. Improvements of endurance performance were correlated with reductions of EEG spectral power at 90 and 120rpm. Whereas high and low cadence training elicit similar improvements in endurance performance, brain cortical activity is especially sensitive to high cadence training. Its reduction can be interpreted in the sense of the neural efficiency hypothesis and might as well influence the sensation of central fatigue positively. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  16. Resonant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation.

    PubMed

    Li, S; Arbuthnott, G W; Jutras, M J; Goldberg, J A; Jaeger, D

    2007-12-01

    Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)-lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.

  17. Correlated energy-spread removal with space charge for high-harmonic generation.

    PubMed

    Hemsing, E; Marinelli, A; Marcus, G; Xiang, D

    2014-09-26

    We study the effect of longitudinal space charge on the correlated energy spread of a relativistic high-brightness electron beam that has been density modulated for the emission of coherent, high-harmonic radiation. We show that, in the case of electron bunching induced by a laser modulator followed by a dispersive chicane, longitudinal space charge forces can act to strongly reduce the induced energy modulation of the beam without a significant reduction in the harmonic bunching content. This effect may be optimized to enhance the output power and overall performance of free-electron lasers that produce coherent light through high-gain harmonic generation. It also increases the harmonic number achievable in these devices, which are otherwise gain-limited by the induced energy modulation from the laser.

  18. High-speed imaging of temporal thermal field in thermoplastic material during flame spread

    NASA Astrophysics Data System (ADS)

    Matsuoka, T.; Yamazaki, T.; Nakamura, Y.

    2017-02-01

    We have developed a real-time holographic interferometry system with high-speed camera in order to visualize two dimensional, time-dependent temperature distributions in gas and solid phases simultaneously during the combustion of transparent thermoplastic material. The ultimate goal of this study is to contribute to upgrade the flame spread modeling at which the complex physical processes (e.g., fuel regression, bubble formation, motion inside the molten layer) have been mostly ignored, although those effect are not so well-known and not well-studied. As first step, thermal response of thermoplastic material subjected to the disturbance in gas phase was investigated. Thick transparent PMMA slab was used as sample specimen and the thermal status in gas, molten and solid phases over spreading flame downwardly was examined. Whole optical set was carefully arranged and tuned to obtain satisfactory clear interference fringes appeared in gas and solid phases during the combustion event. Following the disturbance introduced in the system, the time change of refractive index in gas, molten and solid phases and the corresponding temperature distributions was recorded via a high-speed camera. Response delay time was carefully analyzed to discuss the potential role of the liquid phase on the burning character.

  19. High social desirability and prefrontal cortical activity in cancer patients: a preliminary study.

    PubMed

    Tashiro, Manabu; Juengling, Freimut D; Moser, Ernst; Reinhardt, Michael J; Kubota, Kazuo; Yanai, Kazuhiko; Sasaki, Hidetada; Nitzsche, Egbert U; Kumano, Hiroaki; Itoh, Masatoshi

    2003-04-01

    Social desirability is sometimes associated with poor prognosis in cancer patients. Psycho-neuro-immune interaction has been hypothesized as an underlying mechanism of the negative clinical outcome. Purpose of this study was to examine possible effects of high social desirability on the regional brain activity in patients with malignant diseases. Brain metabolism of 16 patients with various malignant diseases was measured by PET with 18F-fluorodeoxyglucose (FDG). Patients were divided into 2 groups using median split on Marlowe & Crown's Social Desirability Scale (MC), controlling for age, gender, and for severity of depression and anxiety, the possible two major influential factors. A group comparison of the regional cerebral activity was calculated on a voxel-by-voxel basis using statistical parametric mapping (SPM). The subgroup comparison showed that the high social desirability was associated with relatively increased metabolism in the cortical regions in the prefrontal, temporal and occipital lobes as well as in the anterior cingulate gyrus. High social desirability seems to be associated with increased activity in the prefrontal and other cortical areas. The finding is in an accordance with previous studies that demonstrated an association between prefrontal damage and anti-social behavior. Functional neuroimaging seems to be useful not only for psychiatric evaluation of major factors such as depression and anxiety but also for further psychosocial factors in cancer patients.

  20. High Incidence and Endemic Spread of NDM-1-Positive Enterobacteriaceae in Henan Province, China

    PubMed Central

    Qin, Shangshang; Fu, Ying; Zhang, Qijing; Qi, Hui; Wen, Jian Guo; Xu, Hui; Xu, Lijuan; Zeng, Li; Tian, Hao; Rong, Lijuan; Li, Yonghong; Shan, Lihong; Xu, Hongde; Yu, Yunsong

    2014-01-01

    The emergence and spread of New Delhi metallo-β-lactamase 1 (NDM-1)-producing carbapenem-resistant Enterobacteriaceae (CRE) present an urgent threat to human health. In China, the blaNDM-1 gene has been reported mostly in Acinetobacter spp. but is rarely found in Enterobacteriaceae. Here, we report a high incidence and endemic spread of NDM-1-producing CRE in Henan Province in China. Sixteen (33.3%) of the 48 CRE isolates obtained from patients during June 2011 to July 2012 were positive for blaNDM-1, and the gene was found to be carried on plasmids of various sizes (∼55 to ∼360 kb). These plasmids were readily transferrable to recipient Escherichia coli by conjugation, conferred resistance to multiple antibiotics, and belonged to multiple replicon types. The blaNDM-1-positive CRE isolates were genetically diverse, and six new multilocus sequence typing (MLST) sequence types were linked to the carriage of NDM-1. Five of the isolates were classified as extensively drug-resistant (XDR) isolates, four of which also carried the fosA3 gene conferring resistance to fosfomycin, an alternative drug for treating infections by CRE. In each blaNDM-1-positive CRE isolate, the blaNDM-1 gene was downstream of an intact ISAba125 element and upstream of the bleMBL gene. Furthermore, gene environment analysis suggested the possible transmission of blaNDM-1-containing sequences from Acinetobacter spp. to Klebsiella pneumoniae and Klebsiella oxytoca. These findings reveal the emergence and active transmission of NDM-1-positive CRE in China and underscore the need for heightened measures to control their further spread. PMID:24777095

  1. High incidence and endemic spread of NDM-1-positive Enterobacteriaceae in Henan Province, China.

    PubMed

    Qin, Shangshang; Fu, Ying; Zhang, Qijing; Qi, Hui; Wen, Jian Guo; Xu, Hui; Xu, Lijuan; Zeng, Li; Tian, Hao; Rong, Lijuan; Li, Yonghong; Shan, Lihong; Xu, Hongde; Yu, Yunsong; Feng, Xianju; Liu, Hong-Min

    2014-08-01

    The emergence and spread of New Delhi metallo-β-lactamase 1 (NDM-1)-producing carbapenem-resistant Enterobacteriaceae (CRE) present an urgent threat to human health. In China, the bla(NDM-1 gene has been reported mostly in Acinetobacter spp. but is rarely found in Enterobacteriaceae. Here, we report a high incidence and endemic spread of NDM-1-producing CRE in Henan Province in China. Sixteen (33.3%) of the 48 CRE isolates obtained from patients during June 2011 to July 2012 were positive for bla(NDM-1), and the gene was found to be carried on plasmids of various sizes (∼ 55 to ∼ 360 kb). These plasmids were readily transferrable to recipient Escherichia coli by conjugation, conferred resistance to multiple antibiotics, and belonged to multiple replicon types. The bla(NDM-1)-positive CRE isolates were genetically diverse, and six new multilocus sequence typing (MLST) sequence types were linked to the carriage of NDM-1. Five of the isolates were classified as extensively drug-resistant (XDR) isolates, four of which also carried the fosA3 gene conferring resistance to fosfomycin, an alternative drug for treating infections by CRE. In each bla(NDM-1)-positive CRE isolate, the bla(NDM-1) gene was downstream of an intact ISAba125 element and upstream of the bleMBL gene. Furthermore, gene environment analysis suggested the possible transmission of bla(NDM-1)-containing sequences from Acinetobacter spp. to Klebsiella pneumoniae and Klebsiella oxytoca. These findings reveal the emergence and active transmission of NDM-1-positive CRE in China and underscore the need for heightened measures to control their further spread.

  2. Cortical cytasters: a highly conserved developmental trait of Bilateria with similarities to Ctenophora

    PubMed Central

    2011-01-01

    Background Cytasters (cytoplasmic asters) are centriole-based nucleation centers of microtubule polymerization that are observable in large numbers in the cortical cytoplasm of the egg and zygote of bilaterian organisms. In both protostome and deuterostome taxa, cytasters have been described to develop during oogenesis from vesicles of nuclear membrane that move to the cortical cytoplasm. They become associated with several cytoplasmic components, and participate in the reorganization of cortical cytoplasm after fertilization, patterning the antero-posterior and dorso-ventral body axes. Presentation of the hypothesis The specific resemblances in the development of cytasters in both protostome and deuterostome taxa suggest that an independent evolutionary origin is unlikely. An assessment of published data confirms that cytasters are present in several protostome and deuterostome phyla, but are absent in the non-bilaterian phyla Cnidaria and Ctenophora. We hypothesize that cytasters evolved in the lineage leading to Bilateria and were already present in the most recent common ancestor shared by protostomes and deuterostomes. Thus, cytasters would be an ancient and highly conserved trait that is homologous across the different bilaterian phyla. The alternative possibility is homoplasy, that is cytasters have evolved independently in different lineages of Bilateria. Testing the hypothesis So far, available published information shows that appropriate observations have been made in eight different bilaterian phyla. All of them present cytasters. This is consistent with the hypothesis of homology and conservation. However, there are several important groups for which there are no currently available data. The hypothesis of homology predicts that cytasters should be present in these groups. Increasing the taxonomic sample using modern techniques uniformly will test for evolutionary patterns supporting homology, homoplasy, or secondary loss of cytasters. Implications of

  3. Cortical cytasters: a highly conserved developmental trait of Bilateria with similarities to Ctenophora.

    PubMed

    Salinas-Saavedra, Miguel; Vargas, Alexander O

    2011-12-01

    Cytasters (cytoplasmic asters) are centriole-based nucleation centers of microtubule polymerization that are observable in large numbers in the cortical cytoplasm of the egg and zygote of bilaterian organisms. In both protostome and deuterostome taxa, cytasters have been described to develop during oogenesis from vesicles of nuclear membrane that move to the cortical cytoplasm. They become associated with several cytoplasmic components, and participate in the reorganization of cortical cytoplasm after fertilization, patterning the antero-posterior and dorso-ventral body axes. The specific resemblances in the development of cytasters in both protostome and deuterostome taxa suggest that an independent evolutionary origin is unlikely. An assessment of published data confirms that cytasters are present in several protostome and deuterostome phyla, but are absent in the non-bilaterian phyla Cnidaria and Ctenophora. We hypothesize that cytasters evolved in the lineage leading to Bilateria and were already present in the most recent common ancestor shared by protostomes and deuterostomes. Thus, cytasters would be an ancient and highly conserved trait that is homologous across the different bilaterian phyla. The alternative possibility is homoplasy, that is cytasters have evolved independently in different lineages of Bilateria. So far, available published information shows that appropriate observations have been made in eight different bilaterian phyla. All of them present cytasters. This is consistent with the hypothesis of homology and conservation. However, there are several important groups for which there are no currently available data. The hypothesis of homology predicts that cytasters should be present in these groups. Increasing the taxonomic sample using modern techniques uniformly will test for evolutionary patterns supporting homology, homoplasy, or secondary loss of cytasters. If cytasters are homologous and highly conserved across bilateria, their potential

  4. Inward spread of activation in frog muscle fibres investigated by means of high-speed microcinematography

    PubMed Central

    Sugi, H.

    1974-01-01

    1. Single fast muscle fibres of the frog were locally activated by applying current pulses to a pipette whose tip was in contact with the fibre surface, and the resulting local contractions were recorded with a high-speed ciné-camera at 1000-3000 frames/sec. 2. In some but not all of the fibres examined, a moderate membrane depolarization of 20-30 mV initiated a phasic type of local contraction, which showed a definite threshold and relaxed spontaneously while the depolarization still continued. 3. The phasic contraction was sometimes followed by a smaller steady contraction, which lasted as long as the depolarization went on and was regarded to be indentical with the graded type of local contraction. 4. With pipettes of 20-40 μm diameter, the phasic contraction was first initiated at the depolarized fibre surface, and spread to some extent inwards with a velocity of 0·7-2 cm/sec at 18-26° C. The velocity of inward spread of contraction had a Q10 of about 2·3. 5. With larger pipettes of more than 50-60 μm diameter, the phasic response was first initiated at the inner part definitely distant from the fibre surface, and the extent of contraction was greater at this part than at the superficial part during the course of the response. Furthermore, with depolarizations of nearly the threshold value, the steady contraction following the phasic one was seen only at the inner part, suggesting the reversal of the gradient of depolarization along the T tubules. 6. The phasic contraction spread inwards or transversely with a considerable decrement. The response spreading across the whole diameter of the fibre could be observed only in some cases. 7. The phasic response was not always sensitive to tetrodotoxin or to the removal of external sodium ions. 8. These results not only give information about the nature of the regenerative mechanism within the T system, but also suggest that the organization of the T tubule network is such that the electrotonic depolarization

  5. High fidelity point-spread function retrieval in the presence of electrostatic, hysteretic pixel response

    NASA Astrophysics Data System (ADS)

    Rasmussen, Andrew; Guyonnet, Augustin; Lage, Craig; Antilogus, Pierre; Astier, Pierre; Doherty, Peter; Gilmore, Kirk; Kotov, Ivan; Lupton, Robert; Nomerotski, Andrei; O'Connor, Paul; Stubbs, Christopher; Tyson, Anthony; Walter, Christopher

    2016-08-01

    We employ electrostatic conversion drift calculations to match CCD pixel signal covariances observed in at field exposures acquired using candidate sensor devices for the LSST Camera.1, 2 We thus constrain pixel geometry distortions present at the end of integration, based on signal images recorded. We use available data from several operational voltage parameter settings to validate our understanding. Our primary goal is to optimize flux point spread function (FPSF) estimation quantitatively, and thereby minimize sensor-induced errors which may limit performance in precision astronomy applications. We consider alternative compensation scenarios that will take maximum advantage of our understanding of this underlying mechanism in data processing pipelines currently under development. To quantitatively capture the pixel response in high-contrast/high dynamic range operational extrema, we propose herein some straightforward laboratory tests that involve altering the time order of source illumination on sensors, within individual test exposures. Hence the word hysteretic in the title of this paper.

  6. Fast and slow spreading ridges - Structure and hydrothermal activity, ultramafic topographic highs, and CH4 output

    NASA Astrophysics Data System (ADS)

    Bougault, Henri; Charlou, Jean-Luc; Fouquet, Yves; Needham, Hubert D.; Vaslet, Nathalie; Appriou, Pierre; Baptiste, Philippe J.; Rona, Peter A.; Dmitriev, Leonid; Silant'ev, Sergej

    1993-06-01

    Different parts of the world ridge system have quite different morphologies, which reflect different constructional processes. It appears that hydrothermal circulation at all spreading centers is an important exchange process between the ocean and the newly formed oceanic crust. This hydrothermal circulation may vary according to morphology and crustal composition and may also affect ridge constructional processes. The TAG and Snake Pit hydrothermal sites on the Mid-Atlantic Ridge (MAR) display Mn/CH4 ratios in overlying seawater similar to those of nonsedimented East Pacific Rise sites, i.e., about 0.2 mol/L. In contrast, large methane anomalies with very low Mn/CH4 ratios of 0.005 mol/L are associated with ultramafic topographic highs near 15 deg N, close to the axis and on ultramafic walls of the rift valley. The association of ultramafic bodies and CH4 anomalies in seawater indicates active serpentinization processes. CH4 is produced during serpentinization according to the Fisher-Tropsch reaction. Changes of mechanical properties and of density of uplifted deep material in the accreting plate boundary zone caused by serpentinization may play an important role in the construction of slow spreading ridges.

  7. Different modalities of painful somatosensory stimulations affect anticipatory cortical processes: a high-resolution EEG study.

    PubMed

    Babiloni, Claudio; Brancucci, Alfredo; Capotosto, Paolo; Del Percio, Claudio; Romani, Gian Luca; Arendt-Nielsen, Lars; Rossini, Paolo Maria

    2007-03-15

    Pain sensation is characterized by multiple features that allow to differentiate pricking, burning, aching, stinging, and electrical shock. These features are sub-served by neural pathways that might give flexibility and selectivity to the cerebral anticipatory processes. In this line, the present high-resolution electroencephalography (EEG) study tested the hypothesis that the anticipatory cortical processes are stronger for painful thermal (biologically relevant) than electrical ("artificial") stimuli with similar intensity. EEG data (128 electrodes) were recorded in normal subjects during the expectancy of painful electrical or laser stimuli (visual omitted stimulus paradigm; interval between two painful stimuli: 16s), delivered over the median nerve region of the right arm (nonpainful stimuli as controls). After each stimulus, the subject reported the perceived stimulus intensity. Surface Laplacian estimation of the EEG data spatially enhanced the anticipatory stimulus-preceding negativity (SPN), which reflects motivational relevance of the stimulus. Subjects perceived no difference in the intensity of the electrical versus laser stimuli in both painful and nonpainful conditions. However, the anticipatory SPN appeared over large scalp regions before painful laser but not electrical stimulation. The same was true for the nonpainful stimulations. The present results suggest that the motivational anticipatory cortical processes are induced by nonpainful and painful biologically/ecologically relevant laser stimuli rather than by "artificial" electrical stimuli with similar intensity.

  8. Cortical characterization of the perception of intelligible and unintelligible speech measured via high-density electroencephalography.

    PubMed

    Utianski, Rene L; Caviness, John N; Liss, Julie M

    2015-01-01

    High-density electroencephalography was used to evaluate cortical activity during speech comprehension via a sentence verification task. Twenty-four participants assigned true or false to sentences produced with 3 noise-vocoded channel levels (1--unintelligible, 6--decipherable, 16--intelligible), during simultaneous EEG recording. Participant data were sorted into higher- (HP) and lower-performing (LP) groups. The identification of a late-event related potential for LP listeners in the intelligible condition and in all listeners when challenged with a 6-Ch signal supports the notion that this induced potential may be related to either processing degraded speech, or degraded processing of intelligible speech. Different cortical locations are identified as neural generators responsible for this activity; HP listeners are engaging motor aspects of their language system, utilizing an acoustic-phonetic based strategy to help resolve the sentence, while LP listeners do not. This study presents evidence for neurophysiological indices associated with more or less successful speech comprehension performance across listening conditions.

  9. Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity.

    PubMed

    Just, Marcel Adam; Cherkassky, Vladimir L; Keller, Timothy A; Minshew, Nancy J

    2004-08-01

    The brain activation of a group of high-functioning autistic participants was measured using functional MRI during sentence comprehension and the results compared with those of a Verbal IQ-matched control group. The groups differed in the distribution of activation in two of the key language areas. The autism group produced reliably more activation than the control group in Wernicke's (left laterosuperior temporal) area and reliably less activation than the control group in Broca's (left inferior frontal gyrus) area. Furthermore, the functional connectivity, i.e. the degree of synchronization or correlation of the time series of the activation, between the various participating cortical areas was consistently lower for the autistic than the control participants. These findings suggest that the neural basis of disordered language in autism entails a lower degree of information integration and synchronization across the large-scale cortical network for language processing. The article presents a theoretical account of the findings, related to neurobiological foundations of underconnectivity in autism.

  10. A high-DC-voltage GaAs photoemission gun: Transverse emittance and momentum spread measurements

    SciTech Connect

    Engwall, D.; Bohn, C.; Cardman, L.

    1997-06-01

    We have built a high-DC-voltage photoemission gun and a diagnostic beamline permitting us to measure rms transverse emittance ({epsilon}{sub x}) and rms momentum spread ({delta}) of short-duration electron pulses produced by illuminating the cathode with light from a mode-locked, frequency-doubled Nd:YLF laser. The electron gun is a GaAs photocathode source designed to operate at 500kV. We have measured {epsilon}{sub x} and {delta} for conditions ranging from emittance-dominated to space-charge-dominated. We report these measurements as functions of microbunch charge for different beam radii, pulse lengths, and voltages/field gradients at the cathode, and compare them with PARMELA calculations.

  11. Limiting the spread of highly resistant hospital-acquired microorganisms via critical care transfers: a simulation study.

    PubMed

    Karkada, Umanka H; Adamic, Lada A; Kahn, Jeremy M; Iwashyna, Theodore J

    2011-10-01

    Hospital-acquired infections with highly resistant organisms are an important problem among critically ill patients. Control of these organisms has largely focused within individual hospitals. We examine the extent to which transfers of critically ill patients could be a vector for the wide spread of highly resistant organisms, and compare the efficiency of different approaches to targeting infection control resources. We analyzed the network of interhospital transfers of intensive care unit patients in 2005 US Medicare data and 2004-2006 Pennsylvania all-payer data. We simulated the spread of highly resistant hospital-acquired infections by randomly choosing a single hospital to develop a highly resistant organism and following the spread of infection or colonization throughout the network under varying strategies of infection control and varying levels of infectivity. Critical care transfers could spread a highly resistant organism between any two US hospitals in a median of 3 years. Hospitals varied substantially in their importance to limiting potential spread. Targeting resources to a small subset of hospitals on the basis of their position in the transfer network was 16 times more efficient than distributing infection control resources uniformly. Within any set of targeted hospitals, the best strategy for infection control heavily concentrated resources at a few particularly important hospitals, regardless of level of infectivity. Critical care transfers provide a plausible vector for widespread dissemination of highly resistant hospital-acquired microorganisms. Infection control efforts can be made more efficient by selectively targeting hospitals most important for transmission.

  12. Multivariate high-dimensional cortical folding analysis, combining complexity and shape, in neonates with congenital heart disease.

    PubMed

    Awate, Suyash P; Yushkevich, Paul; Song, Zhuang; Licht, Daniel; Gee, James C

    2009-01-01

    The paper presents a novel statistical framework for cortical folding pattern analysis that relies on a rich multivariate descriptor of folding patterns in a region of interest (ROI). The ROI-based approach avoids problems faced by spatial-normalization-based approaches stemming from the severe deficiency of homologous features between typical human cerebral cortices. Unlike typical ROI-based methods that summarize folding complexity or shape by a single number, the proposed descriptor unifies complexity and shape of the surface in a high-dimensional space. In this way, the proposed framework couples the reliability of ROI-based analysis with the richness of the novel cortical folding pattern descriptor. Furthermore, the descriptor can easily incorporate additional variables, e.g. cortical thickness. The paper proposes a novel application of a nonparametric permutation-based approach for statistical hypothesis testing for any multivariate high-dimensional descriptor. While the proposed framework has a rigorous theoretical underpinning, it is straightforward to implement. The framework is validated via simulated and clinical data. The paper is the first to quantitatively evaluate cortical folding in neonates with complex congenital heart disease.

  13. Worldwide Alien Invasion: A Methodological Approach to Forecast the Potential Spread of a Highly Invasive Pollinator

    PubMed Central

    2016-01-01

    The ecological impacts of alien species invasion are a major threat to global biodiversity. The increasing number of invasion events by alien species and the high cost and difficulty of eradicating invasive species once established require the development of new methods and tools for predicting the most susceptible areas to invasion. Invasive pollinators pose serious threats to biodiversity and human activity due to their close relationship with many plants (including crop species) and high potential competitiveness for resources with native pollinators. Although at an early stage of expansion, the bumblebee species Bombus terrestris is becoming a representative case of pollinator invasion at a global scale, particularly given its high velocity of invasive spread and the increasing number of reports of its impacts on native bees and crops in many countries. We present here a methodological framework of habitat suitability modeling that integrates new approaches for detecting habitats that are susceptible to Bombus terrestris invasion at a global scale. Our approach did not include reported invaded locations in the modeling procedure; instead, those locations were used exclusively to evaluate the accuracy of the models in predicting suitability over regions already invaded. Moreover, a new and more intuitive approach was developed to select the models and evaluate different algorithms based on their performance and predictive convergence. Finally, we present a comprehensive global map of susceptibility to Bombus terrestris invasion that highlights priority areas for monitoring. PMID:26882479

  14. Worldwide Alien Invasion: A Methodological Approach to Forecast the Potential Spread of a Highly Invasive Pollinator.

    PubMed

    Acosta, André L; Giannini, Tereza C; Imperatriz-Fonseca, Vera L; Saraiva, Antonio M

    2016-01-01

    The ecological impacts of alien species invasion are a major threat to global biodiversity. The increasing number of invasion events by alien species and the high cost and difficulty of eradicating invasive species once established require the development of new methods and tools for predicting the most susceptible areas to invasion. Invasive pollinators pose serious threats to biodiversity and human activity due to their close relationship with many plants (including crop species) and high potential competitiveness for resources with native pollinators. Although at an early stage of expansion, the bumblebee species Bombus terrestris is becoming a representative case of pollinator invasion at a global scale, particularly given its high velocity of invasive spread and the increasing number of reports of its impacts on native bees and crops in many countries. We present here a methodological framework of habitat suitability modeling that integrates new approaches for detecting habitats that are susceptible to Bombus terrestris invasion at a global scale. Our approach did not include reported invaded locations in the modeling procedure; instead, those locations were used exclusively to evaluate the accuracy of the models in predicting suitability over regions already invaded. Moreover, a new and more intuitive approach was developed to select the models and evaluate different algorithms based on their performance and predictive convergence. Finally, we present a comprehensive global map of susceptibility to Bombus terrestris invasion that highlights priority areas for monitoring.

  15. High-resolution interferometric radar images of equatorial spread F scattering structures using Capon's method

    NASA Astrophysics Data System (ADS)

    Zewdie, G. K.; Rodrigues, F. S.; Paula, E. R.

    2015-12-01

    Coherent backscatter radar imaging techniques use measurements made by multiple antenna baselines (visibility estimates) to infer the spatial distribution of the scatterers (brightness function) responsible for the observed echoes. It has been proposed that the Capon method for spectral estimation can be used for high-resolution estimation of the brightness distribution. We investigate the application of the Capon method to measurements made by a small (7-baseline) 30 MHz ionospheric coherent backscatter radar interferometer in Sao Luis, Brazil. The longest baseline of the interferometer is only 15 times the wavelength of radar signal (10 m), and the ionospheric radar soundings have been made using only 4-8 kW transmitters. Nevertheless, we have been able to obtain high-resolution (kilometric scales in the zonal direction) images of scattering structures during equatorial spread F (ESF) events over a wide field of view (+/- 10 degrees off zenith). We will present numerical simulations demonstrating the performance of the technique for the Sao Luis radar setup as well as results of the Capon technique applied to actual measurements. We will discuss the behavior of the ESF scattering structures as seen in the Capon images. The high-resolution images can assist our interpretation of plasma instabilities in the equatorial ionosphere and serve to test our ability to model the behavior of ionospheric irregularities during space weather events such as those associated with ESF.

  16. A preliminary transcranial magnetic stimulation study of cortical inhibition and excitability in high-functioning autism and Asperger disorder.

    PubMed

    Enticott, Peter G; Rinehart, Nicole J; Tonge, Bruce J; Bradshaw, John L; Fitzgerald, Paul B

    2010-08-01

    Controversy surrounds the distinction between high-functioning autism (HFA) and Asperger disorder, but motor abnormalities are associated features of both conditions. This study examined motor cortical inhibition and excitability in HFA and Asperger disorder using transcranial magnetic stimulation (TMS). Participants were diagnosed by experienced clinicians strictly according to DSM-IV criteria. Participants with HFA (nine males, two females; mean age 16y 8mo, SD 4y 5mo) or Asperger disorder (11 males, three females; mean age 19y 1mo, SD 4y 2mo) and neurotypical participants (eight males, three females; mean age 19y 0mo, SD 3y 1mo) were administered a paired-pulse TMS paradigm intended to assess motor cortical inhibition and excitability. Responses to TMS were recorded by electromyography. Cortical inhibition was significantly reduced in the HFA group compared with both the Asperger disorder (p<0.001) and neurotypical (p<0.001) groups, suggesting disruption of activity at gamma-aminobutyric acid A (GABA(A)) receptors. There was no group difference in cortical excitability. Cortical inhibition deficits may underlie motor dysfunction in autism, and perhaps even relate to specific clinical symptoms (e.g. repetitive behaviours). These findings provide novel evidence for a possible neurobiological dissociation between HFA and Asperger disorder based on GABAergic function.

  17. High frequency activity overriding cortico-cortical evoked potentials reflects altered excitability in the human epileptic focus.

    PubMed

    Kobayashi, Katsuya; Matsumoto, Riki; Matsuhashi, Masao; Usami, Kiyohide; Shimotake, Akihiro; Kunieda, Takeharu; Kikuchi, Takayuki; Yoshida, Kazumichi; Mikuni, Nobuhiro; Miyamoto, Susumu; Fukuyama, Hidenao; Takahashi, Ryosuke; Ikeda, Akio

    2017-09-01

    We aimed to clarify that high frequency activity (HFA) of cortico-cortical evoked potentials (CCEPs), elicited by single pulse electrical stimulation (SPES), reflects cortical excitability. We recruited 16 patients with refractory partial epilepsy who had chronic subdural electrode implantation for presurgical evaluation. A repetitive SPES was given to (1) the seizure onset zone (SOZ) and (2) the control cortices (non-seizure onset zone: nSOZ). CCEPs were recorded from the neighboring cortices within SOZ and nSOZ. We applied short-time Fourier transform to obtain the induced responses for the timing of early (<50ms after SPES) and late CCEP components and analyzed the logarithmic power change for ripple (<200Hz) and fast ripple (>200Hz) bands. Twenty-one clear CCEPs were recorded for both the SOZ and nSOZ. The HFA power of early CCEPs in SOZ significantly increased compared to that in nSOZ in both frequency bands, particularly in mesial temporal lobe epilepsy (MTLE). Similar to the features of spontaneous pathological HFOs, the power of stimulus-induced HFAs in SOZ were greater than that outside SOZ, particularly in MTLE. HFA overriding CCEPs can be a surrogate marker of cortical excitability in epileptic focus. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  18. High connectivity between reduced cortical thickness and disrupted white matter tracts in long-standing type 1 diabetes.

    PubMed

    Franc, Daniel T; Kodl, Christopher T; Mueller, Bryon A; Muetzel, Ryan L; Lim, Kelvin O; Seaquist, Elizabeth R

    2011-01-01

    Previous studies have observed disruptions in brain white and gray matter structure in individuals with type 1 diabetes, and these structural differences have been associated with neurocognitive testing deficiencies. This study investigated the relationship between cerebral cortical thickness reductions and white matter microstructural integrity loss in a group of patients with type 1 diabetes and in healthy control subjects using diffusion tensor imaging (DTI). Twenty-five subjects with type 1 diabetes for at least 15 years and 25 age- and sex-matched control subjects underwent structural T1 and proton-density and DTI on a 3.0 Tesla scanner. Fractional anisotropy measurements were made on major cerebral white matter tracts, and DTI tractography was performed to identify cortical regions with high connectivity to these tracts. Posterior white matter tracts with reduced fractional anisotropy (optic radiations, posterior corona radiata, and the splenium region of the corpus callosum) were found to have high connectivity with a number of posterior cortical regions, including the cuneus, precuneus, fusiform, and posterior parietal cortical regions. A significant reduction in cortical thickness in the diabetic group was observed in the regions with high connectivity to the optic radiations and posterior corona radiata tracts (P < 0.05). The direct relationship between white and gray matter structural pathology has not been previously demonstrated in subjects with long-standing type 1 diabetes. The relationship between posterior white matter microstructural integrity disruption and lower cortical thickness demonstrated using a novel DTI connectivity technique suggests a common or interrelated pathophysiological mechanism in type 1 diabetes.

  19. Cortical mapping and frameless stereotactic navigation in the high-field intraoperative magnetic resonance imaging suite

    PubMed Central

    Weingarten, David M.; Asthagiri, Ashok R.; Butman, John A.; Sato, Susumu; Wiggs, Edythe A.; Damaska, Bonita; Heiss, John D.

    2013-01-01

    Frameless stereotactic neuronavigation provides tracking of surgical instruments on radiographic images and orients the surgeon to tumor margins at surgery. Bipolar electrical stimulation mapping (ESM) delineates safe limits for resection of brain tumors adjacent to eloquent cortex. These standard techniques could complement the capability of intraoperative MR (iMR) imaging to evaluate for occult residual disease during surgery and promote more complete tumor removal. The use of frameless neuronavigation in the high-field iMR imaging suite requires that a few pieces of standard equipment be replaced by nonferromagnetic instruments. Specific use of ESM in a high-field iMR imaging suite has not been reported in the literature. To study whether frameless neuronavigation and electrical stimulation mapping could be successfully integrated in the high-field iMR imaging suite, the authors employed these modalities in 10 consecutive cases involving patients undergoing conscious craniotomy for primary brain tumors located in or adjacent to eloquent cortices. Equipment included a custom high-field MR imaging–compatible head holder and dynamic reference frame attachment, a standard MR imaging–compatible dynamic reference frame, a standard MR imaging machine with a table top that could be translated to a pedestal outside the 5-gauss line for the operative intervention, and standard neuronavigational and cortical stimulation equipment. Both ESM and frameless stereotactic guidance were performed outside the 5-gauss line. The presence of residual neoplasm was evaluated using iMR imaging; resection was continued until eloquent areas were encountered or iMR imaging confirmed complete removal of any residual tumor. Mapping identified essential language (5 patients), sensory (6), and motor (7) areas. The combined use of frameless stereotactic navigation, ESM, and iMR imaging resulted in complete radiographic resection in 7 cases and resection to an eloquent margin in 3 cases

  20. Cortical Source Analysis of High-Density EEG Recordings in Children

    PubMed Central

    Bathelt, Joe; O'Reilly, Helen; de Haan, Michelle

    2014-01-01

    EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and signal processing make it possible to exploit information from other imaging modalities like structural MRI that provide high spatial resolution to overcome this constraint1. This is especially useful for investigations that require high resolution in the temporal as well as spatial domain. In addition, due to the easy application and low cost of EEG recordings, EEG is often the method of choice when working with populations, such as young children, that do not tolerate functional MRI scans well. However, in order to investigate which neural substrates are involved, anatomical information from structural MRI is still needed. Most EEG analysis packages work with standard head models that are based on adult anatomy. The accuracy of these models when used for children is limited2, because the composition and spatial configuration of head tissues changes dramatically over development3.  In the present paper, we provide an overview of our recent work in utilizing head models based on individual structural MRI scans or age specific head models to reconstruct the cortical generators of high density EEG. This article describes how EEG recordings are acquired, processed, and analyzed with pediatric populations at the London Baby Lab, including laboratory setup, task design, EEG preprocessing, MRI processing, and EEG channel level and source analysis.  PMID:25045930

  1. Variation in the topography of the speech production cortex verified by cortical stimulation and high gamma activity.

    PubMed

    Babajani-Feremi, Abbas; Rezaie, Roozbeh; Narayana, Shalini; Choudhri, Asim F; Fulton, Stephen P; Boop, Frederick A; Wheless, James W; Papanicolaou, Andrew C

    2014-12-17

    In this study, we have addressed the question of functional brain reorganization for language in the presence and absence of anatomical lesions in two patients with epilepsy using cortical stimulation mapping and high gamma (HG) activity in subdural grid recordings. In both, the expressive language cortex was defined as the cortical patch below the electrode(s) that when stimulated resulted in speech arrest, and during speech expression tasks generated HG activity. This patch fell within the borders of Broca's area, as defined anatomically, in the case of the patient with a lesion, but outside that area in the other, lesion-free patient. Such results highlight the necessity for presurgical language mapping in all cases of surgery involving the language-dominant hemisphere and suggest that HG activity during expressive language tasks can be informative and helpful in conjunction with cortical stimulation mapping for expressive language mapping.

  2. Improved accuracy of cortical bone mineralization measured by polychromatic microcomputed tomography using a novel high mineral density composite calibration phantom

    SciTech Connect

    Deuerling, Justin M.; Rudy, David J.; Niebur, Glen L.; Roeder, Ryan K.

    2010-09-15

    Purpose: Microcomputed tomography (micro-CT) is increasingly used as a nondestructive alternative to ashing for measuring bone mineral content. Phantoms are utilized to calibrate the measured x-ray attenuation to discrete levels of mineral density, typically including levels up to 1000 mg HA/cm{sup 3}, which encompasses levels of bone mineral density (BMD) observed in trabecular bone. However, levels of BMD observed in cortical bone and levels of tissue mineral density (TMD) in both cortical and trabecular bone typically exceed 1000 mg HA/cm{sup 3}, requiring extrapolation of the calibration regression, which may result in error. Therefore, the objectives of this study were to investigate (1) the relationship between x-ray attenuation and an expanded range of hydroxyapatite (HA) density in a less attenuating polymer matrix and (2) the effects of the calibration on the accuracy of subsequent measurements of mineralization in human cortical bone specimens. Methods: A novel HA-polymer composite phantom was prepared comprising a less attenuating polymer phase (polyethylene) and an expanded range of HA density (0-1860 mg HA/cm{sup 3}) inclusive of characteristic levels of BMD in cortical bone or TMD in cortical and trabecular bone. The BMD and TMD of cortical bone specimens measured using the new HA-polymer calibration phantom were compared to measurements using a conventional HA-polymer phantom comprising 0-800 mg HA/cm{sup 3} and the corresponding ash density measurements on the same specimens. Results: The HA-polymer composite phantom exhibited a nonlinear relationship between x-ray attenuation and HA density, rather than the linear relationship typically employed a priori, and obviated the need for extrapolation, when calibrating the measured x-ray attenuation to high levels of mineral density. The BMD and TMD of cortical bone specimens measured using the conventional phantom was significantly lower than the measured ash density by 19% (p<0.001, ANCOVA) and 33% (p<0

  3. Stochastic spatio-temporal modelling of African swine fever spread in the European Union during the high risk period.

    PubMed

    Nigsch, Annette; Costard, Solenne; Jones, Bryony A; Pfeiffer, Dirk U; Wieland, Barbara

    2013-03-01

    African swine fever (ASF) is a notifiable viral pig disease with high mortality and serious socio-economic consequences. Since ASF emerged in Georgia in 2007 the disease has spread to several neighbouring countries and cases have been detected in areas bordering the European Union (EU). It is uncertain how fast the virus would be able to spread within the unrestricted European trading area if it were introduced into the EU. This project therefore aimed to develop a model for the spread of ASF within and between the 27 Member States (MS) of the EU during the high risk period (HRP) and to identify MS during that period would most likely contribute to ASF spread ("super-spreaders") or MS that would most likely receive cases from other MS ("super-receivers"). A stochastic spatio-temporal state-transition model using simulated individual farm records was developed to assess silent ASF virus spread during different predefined HRPs of 10-60 days duration. Infection was seeded into farms of different pig production types in each of the 27 MS. Direct pig-to-pig transmission and indirect transmission routes (pig transport lorries and professional contacts) were considered the main pathways during the early stages of an epidemic. The model was parameterised using data collated from EUROSTAT, TRACES, a questionnaire sent to MS, and the scientific literature. Model outputs showed that virus circulation was generally limited to 1-2 infected premises per outbreak (95% IQR: 1-4; maximum: 10) with large breeder farms as index case resulting in most infected premises. Seven MS caused between-MS spread due to intra-Community trade during the first 10 days after seeding infection. For a HRP of 60 days from virus introduction, movements of infected pigs will originate at least once from 16 MS, with 6 MS spreading ASF in more than 10% of iterations. Two thirds of all intra-Community spread was linked to six trade links only. Denmark, the Netherlands, Lithuania and Latvia were identified

  4. A Preliminary Transcranial Magnetic Stimulation Study of Cortical Inhibition and Excitability in High-Functioning Autism and Asperger Disorder

    ERIC Educational Resources Information Center

    Enticott, Peter G.; Rinehart, Nicole J.; Tonge, Bruce J.; Bradshaw, John L.; Fitzgerald, Paul B.

    2010-01-01

    Aim: Controversy surrounds the distinction between high-functioning autism (HFA) and Asperger disorder, but motor abnormalities are associated features of both conditions. This study examined motor cortical inhibition and excitability in HFA and Asperger disorder using transcranial magnetic stimulation (TMS). Method: Participants were diagnosed by…

  5. A Preliminary Transcranial Magnetic Stimulation Study of Cortical Inhibition and Excitability in High-Functioning Autism and Asperger Disorder

    ERIC Educational Resources Information Center

    Enticott, Peter G.; Rinehart, Nicole J.; Tonge, Bruce J.; Bradshaw, John L.; Fitzgerald, Paul B.

    2010-01-01

    Aim: Controversy surrounds the distinction between high-functioning autism (HFA) and Asperger disorder, but motor abnormalities are associated features of both conditions. This study examined motor cortical inhibition and excitability in HFA and Asperger disorder using transcranial magnetic stimulation (TMS). Method: Participants were diagnosed by…

  6. High Precision Imaging of Microscopic Spread of Glioblastoma with a Targeted Ultrasensitive SERRS Molecular Imaging Probe

    PubMed Central

    Huang, Ruimin; Harmsen, Stefan; Samii, Jason M.; Karabeber, Hazem; Pitter, Kenneth L.; Holland, Eric C.; Kircher, Moritz F.

    2016-01-01

    The dismal prognosis of patients with malignant brain tumors such as glioblastoma multiforme (GBM) is attributed mostly to their diffuse growth pattern and early microscopic tumor spread to distant regions of the brain. Because the microscopic tumor foci cannot be visualized with current imaging modalities, it remains impossible to direct treatments optimally. Here we explored the ability of integrin-targeted surface-enhanced resonance Raman spectroscopy (SERRS) nanoparticles to depict the true tumor extent in a GBM mouse model that closely mimics the pathology in humans. The recently developed SERRS-nanoparticles have a sensitivity of detection in the femtomolar range. An RGD-peptide-conjugated version for integrin-targeting (RGD-SERRS) was compared directly to its non-targeted RAD-SERRS control in the same mice via Raman multiplexing. Pre-blocking with RGD peptide before injection of RGD-SERRS nanoparticles was used to verify the specificity of integrin-targeting. In contrast to the current belief that the enhanced permeability and retention (EPR) effect results in a baseline uptake of nanoparticles regardless of their surface chemistry, integrin-targeting was shown to be highly specific, with markedly lower accumulation after pre-blocking. While the non-targeted SERRS particles enabled delineation of the main tumor, the RGD-SERRS nanoparticles afforded a major improvement in visualization of the true extent and the diffuse margins of the main tumor. This included the detection of unexpected tumor areas distant to the main tumor, tracks of migrating cells of 2-3 cells in diameter, and even isolated distant tumor cell clusters of less than 5 cells. This Raman spectroscopy-based nanoparticle-imaging technology holds promise to allow high precision visualization of the true extent of malignant brain tumors. PMID:27279902

  7. Geology of a dying backarc spreading segment: results of high-density samplings of Godzilla Megamullion

    NASA Astrophysics Data System (ADS)

    Ohara, Y.; Snow, J. E.; Michibayashi, K.; Dick, H. J.; Harigane, Y.; Tani, K.; Yamashita, H.; Ishizuka, O.; Loocke, M. P.; Ishii, T.; Okino, K.

    2011-12-01

    The Godzilla Megamullion is the largest known oceanic core complex (OCC), and is located in an extinct backarc basin in the Philippine Sea: the Parece Vela Basin (PVB). Earlier, based on poorly constrained magnetic data, we believed the basin was active from 26 to 12 Ma at an intermediate-spreading rate of 8.8-7.0 cm/year full-rate (Okino et al. 1998; Ohara et al. 2001, 2003). The tectono-magmatic characteristics of Godzilla Megamullion were thus thought unusual and paradoxical. Although a higher magmatic budget is expected for a fast- to intermediate-spreading ridge, the PVB shows features indicating a smaller magmatic budget, including oceanic core complexes and abundant peridotites and gabbros (Ohara et al., 2001; 2003). Many peridotites in the PVB are much less depleted than those exposed at comparable spreading rates on other mid-ocean ridge systems (Ohara et al. 2001, 2003; Ohara 2006). Zircon U-Pb dating of gabbroic and leucocratic rocks from Godzilla Megamullion now reveals that exhumation of the 125 km long detachment surface lasted for ~4 m.y., with continuous magmatic accretion at the spreading axis (Tani et al., 2011). The estimated denudation rate of the OCC was ~2.5 cm/y; significantly slower than the previous estimate based on magnetic data. The latest magmatism occurred at ~7.9 Ma or later, significantly younger than a previous estimate of 12 Ma. The new age data indicate that the terminal phase of PVB spreading was not at intermediate spreading rates, with a significant decline and asymmetry accompanying formation of Godzilla Megamullion in a "dying" backarc spreading segment. The recent field survey also supports a slow- to ultraslow-spreading environment for Godzilla Megamulllion, including increased melt stagnation in the shallow mantle, and decreasing degree of partial melting of the peridotites towards the termination of Godzilla Megamullion. We will be conducting a cruise (YK11-08) during October 2011 focused on the tectono-magmatic process

  8. Anatidae migration in the western Palearctic and spread of highly pathogenic avian influenza H5NI virus.

    PubMed

    Gilbert, Marius; Xiao, Xiangming; Domenech, Joseph; Lubroth, Juan; Martin, Vincent; Slingenbergh, Jan

    2006-11-01

    During the second half of 2005, highly pathogenic avian influenza (HPAI) H5N1 virus spread rapidly from central Asia to eastern Europe. The relative roles of wild migratory birds and the poultry trade are still unclear, given that little is yet known about the range of virus hosts, precise movements of migratory birds, or routes of illegal poultry trade. We document and discuss the spread of the HPAI H5N1 virus in relation to species-specific flyways of Anatidae species (ducks, geese, and swans) and climate. We conclude that the spread of HPAI H5N1 virus from Russia and Kazakhstan to the Black Sea basin is consistent in space and time with the hypothesis that birds in the Anatidae family have seeded the virus along their autumn migration routes.

  9. Anatidae Migration in the Western Palearctic and Spread of Highly Pathogenic Avian Influenza H5N1 Virus

    PubMed Central

    Xiao, Xiangming; Domenech, Joseph; Lubroth, Juan; Martin, Vincent; Slingenbergh, Jan

    2006-01-01

    During the second half of 2005, highly pathogenic avian influenza (HPAI) H5N1 virus spread rapidly from central Asia to eastern Europe. The relative roles of wild migratory birds and the poultry trade are still unclear, given that little is yet known about the range of virus hosts, precise movements of migratory birds, or routes of illegal poultry trade. We document and discuss the spread of the HPAI H5N1 virus in relation to species-specific flyways of Anatidae species (ducks, geese, and swans) and climate. We conclude that the spread of HPAI H5N1 virus from Russia and Kazakhstan to the Black Sea basin is consistent in space and time with the hypothesis that birds in the Anatidae family have seeded the virus along their autumn migration routes. PMID:17283613

  10. The fabrication of high density nanochannel organic light emitting diodes with reduced charge spreading

    NASA Astrophysics Data System (ADS)

    Trivedi, K.; Bhansali, U. S.; Gnade, B.; Hu, W.

    2009-10-01

    This study reports fabrication and characterization of nanoscale organic light emitting diodes with reduced charge spreading. Nanoimprint lithography is used to make SU-8 nanochannels with ~90° sidewalls into which N'-bis(naphthalen-1-yl)-N,N'-bis(phenyl)benzidine (NPB) and tris-(8-hydroxyquinoline) aluminum (Alq3) are thermally evaporated, to avoid charge spreading. Micron grating devices are fabricated for comparison. Device characteristics show that performance is retained while scaling down to nanochannels, as no geometry dependent trend is observed. Surface potential microscopy (SPM) measurements reveal an identical periodic difference in surface potential for nanochannel and microscale grating devices. The SPM results, together with cross-sectional scanning electron microscopy observation of the physical separation of nanoscale organic light emitting diodes (OLEDs), indicate electrical separation and isolated light emission from nanoscale confined OLEDs with minimized charge spreading.

  11. Generation of induced pluripotent stem cells with high efficiency from human embryonic renal cortical cells

    PubMed Central

    Yao, Ling; Chen, Ruifang; Wang, Pu; Zhang, Qi; Tang, Hailiang; Sun, Huaping

    2016-01-01

    Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts. These iPSCs show pluripotency in vitro and in vivo, as evidenced by expression of pluripotency associated genes, differentiation into three embryonic germ layers by teratoma tests, as well as neuronal fate specification by embryoid body formation. Moreover, the four exogenous genes are effectively silenced in these iPSCs. This study highlights the use of hERCCs to generate highly functional human iPSCs which may aid the study of genetic kidney diseases and accelerate the development of cell-based regenerative therapy. PMID:27904699

  12. Complete sparing of high-contrast color input to motion perception in cortical color blindness.

    PubMed

    Cavanagh, P; Hénaff, M A; Michel, F; Landis, T; Troscianko, T; Intriligator, J

    1998-07-01

    It is widely held that color and motion are processed by separate parallel pathways in the visual system, but this view is difficult to reconcile with the fact that motion can be detected in equiluminant stimuli that are defined by color alone. To examine the relationship between color and motion, we tested three patients who had lost their color vision following cortical damage (central achromatopsia). Despite their profound loss in the subjective experience of color and their inability to detect the motion of faint colors, all three subjects showed surprisingly strong responses to high-contrast, moving color stimuli--equal in all respects to the performance of subjects with normal color vision. The pathway from opponent-color detectors in the retina to the motion analysis areas must therefore be independent of the damaged color centers in the occipitotemporal area. It is probably also independent of the motion analysis area MT/V5, because the contribution of color to motion detection in these patients is much stronger than the color response of monkey area MT.

  13. High Frequency Drift Waves with Wavelengths Below the Ion Gyroradius in Equatorial Spread F

    DTIC Science & Technology

    1978-05-01

    Freidberg and Gerwin, 1977; Gary and Sanderson, 1977) p" r kvdi 1 G = J dt exp iuot + b.(cost -l) - i —— sin t (h) and for...McClure Equatorial Spread F: Implications of VHF Radar Observations, J. Geophys. Res., JJ>, 7199, 1970. Freidberg , J. P., and R. A. Gerwin, Lower

  14. The impact of high grade glial neoplasms on human cortical electrophysiology

    PubMed Central

    Pahwa, Mrinal; Hacker, Carl D.; Bundy, David T.; Breshears, Jonathan D.; Sharma, Mohit; Shimony, Joshua S.; Leuthardt, Eric C.

    2017-01-01

    Objective The brain’s functional architecture of interconnected network-related oscillatory patterns in discrete cortical regions has been well established with functional magnetic resonance imaging (fMRI) studies or direct cortical electrophysiology from electrodes placed on the surface of the brain, or electrocorticography (ECoG). These resting state networks exhibit a robust functional architecture that persists through all stages of sleep and under anesthesia. While the stability of these networks provides a fundamental understanding of the organization of the brain, understanding how these regions can be perturbed is also critical in defining the brain’s ability to adapt while learning and recovering from injury. Methods Patients undergoing an awake craniotomy for resection of a tumor were studied as a unique model of an evolving injury to help define how the cortical physiology and the associated networks were altered by the presence of an invasive brain tumor. Results This study demonstrates that there is a distinct pattern of alteration of cortical physiology in the setting of a malignant glioma. These changes lead to a physiologic sequestration and progressive synaptic homogeneity suggesting that a de-learning phenomenon occurs within the tumoral tissue compared to its surroundings. Significance These findings provide insight into how the brain accommodates a region of “defunctionalized” cortex. Additionally, these findings may have important implications for emerging techniques in brain mapping using endogenous cortical physiology. PMID:28319187

  15. Cortical thickness and trait empathy in patients and people at high risk for alcohol use disorders.

    PubMed

    Schmidt, Tobias; Roser, Patrik; Ze, Oksana; Juckel, Georg; Suchan, Boris; Thoma, Patrizia

    2017-10-03

    Alcoholism not only affects individuals with alcohol use disorder (AUD) but also their biological relatives. This high-risk (HR) group has a higher probability to develop AUD. The aim of our study was to compare cortical thickness (CT) in AUD patients relative to participants with (HR) and without (non-HR) familial predisposition for AUD. We focused on empathy-related brain areas as sociocognitive impairment represents a known risk factor for AUD. We examined 13 individuals with AUD, 14 HR individuals, and 20 non-HR participants using high-resolution T1-weighted magnetic resonance images (3 Tesla) to investigate differences in CT. CT was correlated with self-reported empathy in empathy-related areas. AUD patients showed decreased CT in the left inferior and superior frontal gyri, the right precuneus and bilaterally in the middle frontal gyri/the insula relative to the HR group, and in the left insula, the right middle frontal gyrus and bilaterally in the superior frontal gyrus/the precuneus relative to the non-HR group (all ps < 0.036, all ƞp(2) between 0.161 and 0.375). Reduced CT in inferior, middle, and superior frontal gyri was related to cognitive (all ps < 0.036) and reduced CT in the inferior frontal gyrus to affective (p = 0.031) empathy. We present preliminary evidence of CT reduction in empathy-associated brain regions in patients with AUD relative to healthy participants with and without familial predisposition for AUD. The results have to be interpreted with caution due to low sample sizes and potential confounding effects of medication, gender, and withdrawal.

  16. Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs.

    PubMed

    Chan, Allen W; Mohajerani, Majid H; LeDue, Jeffrey M; Wang, Yu Tian; Murphy, Timothy H

    2015-07-20

    Neuroimaging of spontaneous, resting-state infraslow (<0.1 Hz) brain activity has been used to reveal the regional functional organization of the brain and may lead to the identification of novel biomarkers of neurological disease. However, these imaging studies generally rely on indirect measures of neuronal activity and the nature of the neuronal activity correlate remains unclear. Here we show, using wide-field, voltage-sensitive dye imaging, the mesoscale spatiotemporal structure and pharmacological dependence of spontaneous, infraslow cortical activity in anaesthetized and awake mice. Spontaneous infraslow activity is regionally distinct, correlates with electroencephalography and local field potential recordings, and shows bilateral symmetry between cortical hemispheres. Infraslow activity is attenuated and its functional structure abolished after treatment with voltage-gated sodium channel and glutamate receptor antagonists. Correlation analysis reveals patterns of infraslow regional connectivity that are analogous to cortical motifs observed from higher-frequency spontaneous activity and reflect the underlying framework of intracortical axonal projections.

  17. Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

    PubMed Central

    Chan, Allen W.; Mohajerani, Majid H.; LeDue, Jeffrey M.; Wang, Yu Tian; Murphy, Timothy H.

    2016-01-01

    Neuroimaging of spontaneous, resting-state infraslow (<0.1 Hz) brain activity has been used to reveal the regional functional organization of the brain and may lead to the identification of novel biomarkers of neurological disease. However, these imaging studies generally rely on indirect measures of neuronal activity and the nature of the neuronal activity correlate remains unclear. Here we show, using wide-field, voltage-sensitive dye imaging, the mesoscale spatiotemporal structure and pharmacological dependence of spontaneous, infraslow cortical activity in anaesthetized and awake mice. Spontaneous infraslow activity is regionally distinct, correlates with electroencephalography and local field potential recordings, and shows bilateral symmetry between cortical hemispheres. Infraslow activity is attenuated and its functional structure abolished after treatment with voltage-gated sodium channel and glutamate receptor antagonists. Correlation analysis reveals patterns of infraslow regional connectivity that are analogous to cortical motifs observed from higher-frequency spontaneous activity and reflect the underlying framework of intracortical axonal projections. PMID:26190168

  18. High-frequency and brief-pulse stimulation pulses terminate cortical electrical stimulation-induced afterdischarges.

    PubMed

    Ren, Zhi-Wei; Li, Yong-Jie; Yu, Tao; Ni, Duan-Yu; Zhang, Guo-Jun; Du, Wei; Piao, Yuan-Yuan; Zhou, Xiao-Xia

    2017-06-01

    Brief-pulse stimulation at 50 Hz has been shown to terminate afterdischarges observed in epilepsy patients. However, the optimal pulse stimulation parameters for terminating cortical electrical stimulation-induced afterdischarges remain unclear. In the present study, we examined the effects of different brief-pulse stimulation frequencies (5, 50 and 100 Hz) on cortical electrical stimulation-induced afterdischarges in 10 patients with refractory epilepsy. Results demonstrated that brief-pulse stimulation could terminate cortical electrical stimulation-induced afterdischarges in refractory epilepsy patients. In conclusion, (1) a brief-pulse stimulation was more effective when the afterdischarge did not extend to the surrounding brain area. (2) A higher brief-pulse stimulation frequency (especially 100 Hz) was more likely to terminate an afterdischarge. (3) A low current intensity of brief-pulse stimulation was more likely to terminate an afterdischarge.

  19. A High Performance Spread Spectrum Clock Generator Using Two-Point Modulation Scheme

    NASA Astrophysics Data System (ADS)

    Kao, Yao-Huang; Hsieh, Yi-Bin

    A new spread spectrum clock generator (SSCG) using two-point delta-sigma modulation is presented in this paper. Not only the divider is varied, but also the voltage controlled oscillator is modulated. This technique can enhance the modulation bandwidth so that the effect of EMI suppression is improved with lower order ΣΔ modulator and can simultaneously optimize the jitter and the modulation profile. In addition, the method of two-path is applied to the loop filter to reduce the capacitance value such that the total integration can be achieved. The proposed SSCG has been fabricated in a 0.35μm CMOS process. The clock of 400MHz with center spread ratios of 1.25% and 2.5% are verified. The peak EMI reduction is 19.73dB for the case of 2.5%. The size of chip area is 0.90×0.89mm2.

  20. Crustal accretion at high temperature spreading centres: Rheological control of crustal thickness

    NASA Astrophysics Data System (ADS)

    Schmeling, Harro

    2010-12-01

    New determinations of lateral crustal thickness variations at anomalous oceanic spreading centres such as Iceland have shown that the crust may be thinner at the ridge axis above the plume thickening towards the sides ( Bjarnason and Schmeling, 2009). To understand this behaviour crustal accretion models have been carried out solving the conservation equations of mass, momentum and energy with melting, melt extraction, and feedback of extracted material as newly formed crust for an extending lithosphere system underlain by a hot mantle plume. The dynamics of rifting are thermally and rheologically controlled by the feedback due to accreted new crust. Four accretional modes with characteristic crustal thickness variations are identified depending on the width of the volcanic emplacement zone, the accretional heating rate, which can be associated with the thickness of the surface layer in which magmatic emplacement takes place, and the spreading rate. Mode 1: zero crustal thickness at the spreading axis develops for cool accretion and a wide emplacement zone. Mode 2: strongly or moderately crustal thickening away from the axis develops in case of warm (deep reaching) accretion and wide emplacement zones. Mode 3: nearly constant crustal thickness develops in case of warm (deep reaching) accretion but narrow emplacement zones. Dynamic topography of mode 3 shows only a weak or no regional minimum at all near the axis. Modes 2 or 3 may be identified with the situation in Iceland. Mode 4: a stagnating central crustal block evolves for cool accretion and narrow emplacement. This mode disappears for increasing spreading rates. No accretional mode with maximum crustal thickness above the plume at the rift axis has been found. The absence of mode 1 accretion (with zero crust at ridge axis) on earth may be an indication that in general crustal accretion is not cold (and shallow). The model is also applied to other hotspot-ridge settings (Azores, Galapagos) and suggests modes 2

  1. Modeling the coupled return-spread high frequency dynamics of large tick assets

    NASA Astrophysics Data System (ADS)

    Curato, Gianbiagio; Lillo, Fabrizio

    2015-01-01

    Large tick assets, i.e. assets where one tick movement is a significant fraction of the price and bid-ask spread is almost always equal to one tick, display a dynamics in which price changes and spread are strongly coupled. We present an approach based on the hidden Markov model, also known in econometrics as the Markov switching model, for the dynamics of price changes, where the latent Markov process is described by the transitions between spreads. We then use a finite Markov mixture of logit regressions on past squared price changes to describe temporal dependencies in the dynamics of price changes. The model can thus be seen as a double chain Markov model. We show that the model describes the shape of the price change distribution at different time scales, volatility clustering, and the anomalous decrease of kurtosis. We calibrate our models based on Nasdaq stocks and we show that this model reproduces remarkably well the statistical properties of real data.

  2. High fidelity optogenetic control of individual prefrontal cortical pyramidal neurons in vivo

    PubMed Central

    Cooper, Donald C

    2012-01-01

    Precise spatial and temporal manipulation of neural activity in specific genetically defined cell populations is now possible with the advent of optogenetics. The emerging field of optogenetics consists of a set of naturally-occurring and engineered light-sensitive membrane proteins that are able to activate (e.g. channelrhodopsin-2, ChR2) or silence (e.g. halorhodopsin, NpHR) neural activity. Here we demonstrate the technique and the feasibility of using novel adeno-associated viral (AAV) tools to activate (AAV-CaMKllα-ChR2-eYFP) or silence (AAV-CaMKllα-eNpHR3.0-eYFP) neural activity of rat prefrontal cortical prelimbic (PL) pyramidal neurons  in vivo.  In vivo single unit extracellular recording of ChR2-transduced pyramidal neurons showed that delivery of brief (10 ms) blue (473 nm) light-pulse trains up to 20 Hz via a custom fiber optic-coupled recording electrode (optrode) induced spiking with high fidelity at 20 Hz for the duration of recording (up to two hours in some cases). To silence spontaneously active neurons, we transduced them with the NpHR construct and administered continuous green (532 nm) light to completely inhibit action potential activity for up to 10 seconds with 100% fidelity in most cases. These versatile photosensitive tools, combined with optrode recording methods, provide experimental control over activity of genetically defined neurons and can be used to investigate the functional relationship between neural activity and complex cognitive behavior. PMID:24555016

  3. High fidelity optogenetic control of individual prefrontal cortical pyramidal neurons in vivo.

    PubMed

    Nakamura, Shinya; Baratta, Michael V; Pomrenze, Matthew B; Dolzani, Samuel D; Cooper, Donald C

    2012-01-01

    Precise spatial and temporal manipulation of neural activity in specific genetically defined cell populations is now possible with the advent of optogenetics. The emerging field of optogenetics consists of a set of naturally-occurring and engineered light-sensitive membrane proteins that are able to activate (e.g. channelrhodopsin-2, ChR2) or silence (e.g. halorhodopsin, NpHR) neural activity. Here we demonstrate the technique and the feasibility of using novel adeno-associated viral (AAV) tools to activate (AAV-CaMKllα-ChR2-eYFP) or silence (AAV-CaMKllα-eNpHR3.0-eYFP) neural activity of rat prefrontal cortical prelimbic (PL) pyramidal neurons  in vivo.  In vivo single unit extracellular recording of ChR2-transduced pyramidal neurons showed that delivery of brief (10 ms) blue (473 nm) light-pulse trains up to 20 Hz via a custom fiber optic-coupled recording electrode (optrode) induced spiking with high fidelity at 20 Hz for the duration of recording (up to two hours in some cases). To silence spontaneously active neurons, we transduced them with the NpHR construct and administered continuous green (532 nm) light to completely inhibit action potential activity for up to 10 seconds with 100% fidelity in most cases. These versatile photosensitive tools, combined with optrode recording methods, provide experimental control over activity of genetically defined neurons and can be used to investigate the functional relationship between neural activity and complex cognitive behavior.

  4. Mapping cortical responses to speech using high-density diffuse optical tomography

    PubMed Central

    Hassanpour, Mahlega S.; Eggebrecht, Adam T.; Culver, Joseph P.; Peelle, Jonathan E.

    2015-01-01

    The functional neuroanatomy of speech processing has been investigated using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) for more than 20 years. However, these approaches have relatively poor temporal resolution and/or challenges of acoustic contamination due to the constraints of echoplanar fMRI. Furthermore, these methods are contraindicated because of safety concerns in longitudinal studies and research with children (PET) or in studies of patients with metal implants (fMRI). High-density diffuse optical tomography (HD-DOT) permits presenting speech in a quiet acoustic environment, has excellent temporal resolution relative to the hemodynamic response, and provides noninvasive and metal-compatible imaging. However, the performance of HD-DOT in imaging the brain regions involved in speech processing is not fully established. In the current study, we use an auditory sentence comprehension task to evaluate the ability of HD-DOT to map the cortical networks supporting speech processes. Using sentences with two levels of linguistic complexity, along with a control condition consisting of unintelligible noise-vocoded speech, we recovered a hierarchical organization of the speech network that matches the results of previous fMRI studies. Specifically, hearing intelligible speech resulted in increased activity in bilateral temporal cortex and left frontal cortex, with syntactically complex speech leading to additional activity in left posterior temporal cortex and left inferior frontal gyrus. These results demonstrate the feasibility of using HD-DOT to map spatially distributed brain networks supporting higher-order cognitive faculties such as spoken language. PMID:26026816

  5. An Open Source Based High Content Screening Method for Cell Biology Laboratories Investigating Cell Spreading and Adhesion

    PubMed Central

    Pietro, Maurianne A.; Schwab, Martin E.

    2013-01-01

    Background Adhesion dependent mechanisms are increasingly recognized to be important for a wide range of biological processes, diseases and therapeutics. This has led to a rising demand of pharmaceutical modulators. However, most currently available adhesion assays are time consuming and/or lack sensitivity and reproducibility or depend on specialized and expensive equipment often only available at screening facilities. Thus, rapid and economical high-content screening approaches are urgently needed. Results We established a fully open source high-content screening method for identifying modulators of adhesion. We successfully used this method to detect small molecules that are able to influence cell adhesion and cell spreading of Swiss-3T3 fibroblasts in general and/or specifically counteract Nogo-A-Δ20-induced inhibition of adhesion and cell spreading. The tricyclic anti-depressant clomipramine hydrochloride was shown to not only inhibit Nogo-A-Δ20-induced cell spreading inhibition in 3T3 fibroblasts but also to promote growth and counteract neurite outgrowth inhibition in highly purified primary neurons isolated from rat cerebellum. Conclusions We have developed and validated a high content screening approach that can be used in any ordinarily equipped cell biology laboratory employing exclusively freely available open-source software in order to find novel modulators of adhesion and cell spreading. The versatility and adjustability of the whole screening method will enable not only centers specialized in high-throughput screens but most importantly also labs not routinely employing screens in their daily work routine to investigate the effects of a wide range of different compounds or siRNAs on adhesion and adhesion-modulating molecules. PMID:24205161

  6. Widespread focused improvement: lessons from international health for spreading specific improvements to health services in high-income countries.

    PubMed

    Ovretveit, John

    2011-06-01

    Patients and citizens want more and better healthcare, and want to pay less for it. One way rapidly to respond to these demands is to spread proven or promising improvements in treatments or service delivery models. However, there is little research from high-income countries about effective ways to spread these improvements. In international health there is more experience and knowledge of scale-up, more variety in research approaches used to study the subject, and fewer resources and infrastructure for scaling-up improvements across a nation. This paper draws on reviews of research and experience in international health to contribute to conceptual and empirical knowledge as well as to practical strategies. It describes and illustrates three approaches: hierarchical control, participatory adaptation and facilitated evolution. It presents lessons from international health which could be of use to those studying, choosing, planning and progressing strategies to increase the uptake of proven or promising interventions to health services in high-income countries.

  7. Constructing a High-Resolution Temporal Record of Spreading-Rate Variations Along the Mid-Atlantic Ridge

    NASA Astrophysics Data System (ADS)

    Carchedi, C. J. W.; Dalton, C. A.; Herbert, T.

    2016-12-01

    Paleoclimate records provide an opportunity to investigate links between major changes in Earth's climate and long-term forcing mechanisms. While changes in atmospheric CO2 appear to drive trends in climate, global ocean cooling in the late Miocene remains an enigma: most CO2 proxies do not show a corresponding decline over this period. To improve constraints on the global carbon cycle over this time, we are constructing a new global synthesis of variations in ridge spreading rates with high temporal resolution over the past 20 Myr. We utilize newly available compilations of seafloor fabric and marine magnetic anomalies that are provided by the Global Seafloor Fabric and Magnetic Lineation Data Base Project (Matthews et al., 2011; Seton et al., 2014). Our initial focus is the northern Mid-Atlantic Ridge, where spreading is preserved on both ridge flanks, and dense data sets of magnetic anomalies are available. To obtain accurate and precise values of time, we use a new orbital timescale for magnetic reversal ages. Tectonic flow lines are generated from seafloor fabric, using continuous fracture zones extending from transform faults along the current ridge out to seafloor > 30 Myr. The cumulative distance each point on the flow line has traveled from the ridge is computed. Nearby magnetic anomalies are projected onto the flow line along lines normal to the flow line. Spreading rate as a function of seafloor age is then determined from age-distance relationships; both ridge flanks are treated separately to investigate spreading asymmetry. To improve the profiles' signal to noise ratios, we then stack the anomaly crossings onto composite east and west spreading profiles. Our preliminary analysis shows that spreading rates have decreased significantly from the mid-Miocene to the present, beginning around 15 Ma and experiencing a pronounced reduction during 8 to 5 Ma. This trend mirrors the decline observed in global sea surface temperatures, suggesting that tectonic

  8. High Insulin Levels in KK-Ay Diabetic Mice Cause Increased Cortical Bone Mass and Impaired Trabecular Micro-Structure

    PubMed Central

    Fu, Cen; Zhang, Xiaolin; Ye, Fei; Yang, Jianhong

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia, hyperinsulinemia and complications, including obesity and osteoporosis. Rodents have been widely used to model human T2DM and investigate its effect on the skeleton. We aimed to investigate skeletal alterations in Yellow Kuo Kondo (KK-Ay) diabetic mice displaying high insulin and glucose levels. Bone mineral density (BMD), micro-architecture and bone metabolism-related genes were analyzed. The total femoral areal BMD (aBMD), cortical volumetric BMD (vBMD) and thickness were significantly increased in KK-Ay mice, while the trabecular vBMD and mineralized bone volume/tissue volume (BV/TV), trabecular thickness and number were decreased compared to C57BL mice. The expression of both osteoblast-related genes, such as osteocalcin (OC), bone sialoprotein, Type I Collagen, osteonectin, RUNX2 and OSX, and osteoclast-related genes, such as TRAP and TCIRG, were up-regulated in KK-Ay mice. Correlation analyses showed that serum insulin levels were positively associated with aBMD, cortical vBMD and thickness and negatively associated with trabecular vBMD and micro-architecture. In addition, serum insulin levels were positively related to osteoblast-related and osteoclast-related gene expression. Our data suggest that high insulin levels in KK-Ay diabetic mice may increase cortical bone mass and impair trabecular micro-structure by up-regulating osteoblast-and osteoclast-related gene expression. PMID:25872143

  9. High insulin levels in KK-Ay diabetic mice cause increased cortical bone mass and impaired trabecular micro-structure.

    PubMed

    Fu, Cen; Zhang, Xiaolin; Ye, Fei; Yang, Jianhong

    2015-04-13

    Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia, hyperinsulinemia and complications, including obesity and osteoporosis. Rodents have been widely used to model human T2DM and investigate its effect on the skeleton. We aimed to investigate skeletal alterations in Yellow Kuo Kondo (KK-Ay) diabetic mice displaying high insulin and glucose levels. Bone mineral density (BMD), micro-architecture and bone metabolism-related genes were analyzed. The total femoral areal BMD (aBMD), cortical volumetric BMD (vBMD) and thickness were significantly increased in KK-Ay mice, while the trabecular vBMD and mineralized bone volume/tissue volume (BV/TV), trabecular thickness and number were decreased compared to C57BL mice. The expression of both osteoblast-related genes, such as osteocalcin (OC), bone sialoprotein, Type I Collagen, osteonectin, RUNX2 and OSX, and osteoclast-related genes, such as TRAP and TCIRG, were up-regulated in KK-Ay mice. Correlation analyses showed that serum insulin levels were positively associated with aBMD, cortical vBMD and thickness and negatively associated with trabecular vBMD and micro-architecture. In addition, serum insulin levels were positively related to osteoblast-related and osteoclast-related gene expression. Our data suggest that high insulin levels in KK-Ay diabetic mice may increase cortical bone mass and impair trabecular micro-structure by up-regulating osteoblast-and osteoclast-related gene expression.

  10. The spread of highly pathogenic avian influenza (subtype H5N1) clades in Bangladesh, 2010 and 2011.

    PubMed

    Osmani, Muzaffar G; Ward, Michael P; Giasuddin, Md; Islam, Md Rafiqul; Kalam, Abul

    2014-04-01

    Since the global spread of highly pathogenic avian influenza H5N1 during 2005-2006, control programs have been successfully implemented in most affected countries. HPAI H5N1 was first reported in Bangladesh in 2007, and since then 546 outbreaks have been reported to the OIE. The disease has apparently become endemic in Bangladesh. Spatio-temporal information on 177 outbreaks of HPAI H5N1 occurring between February 2010 and April 2011 in Bangladesh, and 37 of these outbreaks in which isolated H5N1 viruses were phylogenetically characterized to clade, were analyzed. Three clades were identified, 2.2 (21 cases), 2.3.4 (2 cases) and 2.3.2.1 (14 cases). Clade 2.2 was identified throughout the time period and was widely distributed in a southeast-northwest orientation. Clade 2.3.2.1 appeared later and was generally confined to central Bangladesh in a north-south orientation. Based on a direction test, clade 2.2 viruses spread in a southeast-to-northwest direction, whereas clade 2.3.2.1 spread west-to-east. The magnitude of spread of clade 2.3.2.1 was greater relative to clade 2.2 (angular concentration 0.2765 versus 0.1860). In both cases, the first outbreak(s) were identified as early outliers, but in addition, early outbreaks (one each) of clade 2.2 were also identified in central Bangladesh and in northwest Bangladesh, a considerable distance apart. The spread of highly pathogenic avian influenza H5N1 in Bangladesh is characterized by reported long-distance translocation events. This poses a challenge to disease control efforts. Increased enforcement of biosecurity and stronger control of movements between affected farms and susceptible farms, and better surveillance and reporting, is needed. Although the movement of poultry and equipment appears to be a more likely explanation for the patterns identified, the relative contribution of trade and the market chain versus wild birds in spreading the disease needs further investigation.

  11. Estimation of the cortical functional connectivity with the multimodal integration of high-resolution EEG and fMRI data by directed transfer function.

    PubMed

    Babiloni, F; Cincotti, F; Babiloni, C; Carducci, F; Mattia, D; Astolfi, L; Basilisco, A; Rossini, P M; Ding, L; Ni, Y; Cheng, J; Christine, K; Sweeney, J; He, B

    2005-01-01

    Nowadays, several types of brain imaging device are available to provide images of the functional activity of the cerebral cortex based on hemodynamic, metabolic, or electromagnetic measurements. However, static images of brain regions activated during particular tasks do not convey the information of how these regions communicate with each other. In this study, advanced methods for the estimation of cortical connectivity from combined high-resolution electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data are presented. These methods include a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from individual magnetic resonance images, multidipole source model, and regularized linear inverse source estimates of cortical current density. Determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) fMRI. We estimate functional cortical connectivity by computing the directed transfer function (DTF) on the estimated cortical current density waveforms in regions of interest (ROIs) on the modeled cortical mantle. The proposed method was able to unveil the direction of the information flow between the cortical regions of interest, as it is directional in nature. Furthermore, this method allows to detect changes in the time course of information flow between cortical regions in different frequency bands. The reliability of these techniques was further demonstrated by elaboration of high-resolution EEG and fMRI signals collected during visually triggered finger movements in four healthy subjects. Connectivity patterns estimated for this task reveal an involvement of right parietal and bilateral premotor and prefrontal cortical areas. This cortical region involvement resembles that revealed in previous studies where visually triggered finger

  12. Aberrant high-frequency desynchronization of cerebellar cortices in early-onset psychosis.

    PubMed

    Wilson, Tony W; Slason, Erin; Hernandez, Olivia O; Asherin, Ryan; Reite, Martin L; Teale, Peter D; Rojas, Donald C

    2009-10-30

    Sensorimotor integration deficits are routinely observed in both schizophreniform and mood-disordered psychoses. Neurobiological theories of schizophrenia and related psychoses have proposed that aberrations in large-scale cortico-thalamic-cerebellar-thalamic-cortical loops may underlie integration abnormalities, and that such dysfunctional connectivity may be central to the pathophysiology. In this study, we utilized a basic mechanoreception task to probe cortical-cerebellar circuitry in early-onset psychosis. Ten adolescents with psychosis and 10 controls completed unilateral tactile stimulation of the right and left index finger, as whole-head magnetoencephalography (MEG) data were acquired. MEG data were imaged in the frequency domain, using spatial filtering, and the resulting event-related synchronizations and desynchronizations (ERS/ERD) were subjected to voxel-wise analyses of group and task effects using statistical parametric mapping. Our results indicated bilateral ERD activation of cerebellar regions and postcentral gyri in both groups during stimulation of either hand. Interestingly, during left finger stimulations, adolescents with psychosis exhibited greater alpha and gamma ERD activity in right cerebellar cortices relative to controls. Subjects with psychosis also showed greater ERD in bilateral cerebellum and the right postcentral gyrus during right finger stimulation, and these differences were statistically stronger for higher frequency bins. Lastly, controls exhibited greater alpha ERS of the right postcentral gyrus during right finger stimulation. These findings provide new data on the neurodevelopmental trajectory of basic mechanoreception in adolescents, and also indicate aberrant cerebellar functioning in early-onset psychoses, especially in the right cerebellum, which may be the crucial dysfunctional node in cortico-thalamic-cerebellar-thalamic-cortical circuits.

  13. Aberrant high-frequency desynchronization of cerebellar cortices in early-onset psychosis

    PubMed Central

    Wilson, Tony W.; Slason, Erin; Hernandez, Olivia O.; Asherin, Ryan; Reite, Martin L.; Teale, Peter D.; Rojas, Donald C.

    2009-01-01

    Sensorimotor integration deficits are routinely observed in both schizophreniform and mood-disordered psychoses. Neurobiological theories of schizophrenia and related psychoses have proposed aberrations in large scale cortico-thalamic-cerebellar-thalamic-cortical loops may underlie integration abnormalities, and that such dysfunctional connectivity may be central to the pathophysiology. In this study, we utilized a basic mechanoreception task to probe cortical-cerebellar circuitry in early-onset psychosis. Ten adolescents with psychosis and 10 controls completed unilateral tactile stimulation of the right and left index finger, as whole-head magnetoencephalography (MEG) data were acquired. MEG data were imaged in the frequency-domain, using spatial filtering, and the resulting event-related synchronizations and desynchronizations (ERS/ERD) were subjected to voxel-wise analyses of group and task effects using statistical parametric mapping. Our results indicated bilateral ERD activation of cerebellar regions and postcentral gyri in both groups during stimulation of either hand. Interestingly, during left finger stimulations, adolescents with psychosis exhibited greater alpha and gamma ERD activity in right cerebellar cortices relative to controls. Subjects with psychosis also showed greater ERD in bilateral cerebellum and the right postcentral gyrus during right finger stimulation, and these differences were statistically stronger for higher frequency bins. Lastly, controls exhibited greater alpha ERS of the right postcentral gyrus during right finger stimulation. These findings provide new data on the neurodevelopmental trajectory of basic mechanoreception in adolescents, and also indicate aberrant cerebellar functioning in early-onset psychoses, especially in the right cerebellum, which may be the crucial dysfunctional node in cortico-thalamic-cerebellar-thalamic-cortical circuits. PMID:19783411

  14. Cortical excitability changes after high-frequency repetitive transcranial magnetic stimulation for central poststroke pain.

    PubMed

    Hosomi, Koichi; Kishima, Haruhiko; Oshino, Satoru; Hirata, Masayuki; Tani, Naoki; Maruo, Tomoyuki; Yorifuji, Shiro; Yoshimine, Toshiki; Saitoh, Youichi

    2013-08-01

    Central poststroke pain (CPSP) is one of the most refractory chronic pain syndromes. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been demonstrated to provide moderate pain relief for CPSP. However, the mechanism underlying the pain relief remains unclear. The objective of this study was to assess changes in cortical excitability in patients with intractable CPSP before and after rTMS of the primary motor cortex. Subjects were 21 patients with CPSP of the hand who underwent rTMS. The resting motor threshold, the amplitude of the motor evoked potential, duration of the cortical silent period, short interval intracortical inhibition, and intracortical facilitation were measured as parameters of cortical excitability before and after navigation-guided 5 Hz rTMS of the primary motor cortex corresponding to the painful hand. Pain reduction from rTMS was assessed with a visual analog scale. The same parameters were measured in both hemispheres of 8 healthy controls. Eight of 21 patients experienced ≥ 30% pain reduction after rTMS (responders). The resting motor threshold in the patients was higher than those in the controls at baseline (P=.035). Intracortical facilitation in the responders was lower than in the controls and the nonresponders at baseline (P=.035 and P=.019), and significantly increased after rTMS (P=.039). There were no significant differences or changes in the other parameters. Our findings suggest that restoration of abnormal cortical excitability might be one of the mechanisms underlying pain relief as a result of rTMS in CPSP.

  15. D2 dopamine receptors modulate neuronal resonance in subthalamic nucleus and cortical high-voltage spindles through HCN channels.

    PubMed

    Yang, Chen; Yan, Zhiqiang; Zhao, Bo; Wang, Julei; Gao, Guodong; Zhu, Junling; Wang, Wenting

    2016-06-01

    The high-voltage spindles (HVSs), one of the characteristic oscillations that include theta frequencies in the basal ganglia (BG)-cortical system, are involved in immobile behavior and show increasing power in Parkinson's disease (PD). Our previous results suggested that the D2 dopamine receptor might be involved in HVSs modulations in a rat model of PD. Membrane resonance is one of the cellular mechanisms of network oscillation; therefore, we investigated how dopamine modulates the theta frequency membrane resonance of neurons in the subthalamic nucleus (STN), a central pacemaker of BG, and whether such changes in STN neurons subsequently alter HVSs in the BG-cortical system. In particular, we tested whether dopamine modulates HVSs through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels-dependent membrane resonance in STN neurons. We found that an antagonist of D2 receptors, but not of D1 receptors, inhibited membrane resonance and HCN currents of STN neurons through a G-protein activity in acute brain slices. Our further in vivo experiments using local injection of a D2 receptor antagonist or an HCN blocker in STNs of free-moving rats showed an increase in HVSs power and correlation in the BG-cortical system. Local injection of lamotrigine, an HCN agonist, counteracted the effect induced by the D2 antagonist. Taken together, our results revealed a potential cellular mechanism underlying HVSs activity modulation in the BG-cortical system, i.e. tuning HCN activities in STN neurons through dopamine D2 receptors. Our findings might lead to a new direction in PD treatment by providing promising new drug targets for HVSs activity modulation.

  16. High field (9.4 Tesla) magnetic resonance imaging of cortical grey matter lesions in multiple sclerosis.

    PubMed

    Schmierer, Klaus; Parkes, Harold G; So, Po-Wah; An, Shu F; Brandner, Sebastian; Ordidge, Roger J; Yousry, Tarek A; Miller, David H

    2010-03-01

    .9; SD = 5 versus 22.6 ms; SD = 4.7; P < 0.01). Associations were detected between phosphorylated neurofilament and myelin basic protein (r = 0.58, P < 0.01), myelin basic protein and T(2) (r = -0.59, P < 0.01), and neuronal density and T(1) (r = -0.57, P < 0.01). All indices correlated with duration of tissue fixation, however, including the latter in the analysis did not fundamentally affect the associations described. Our data show that T(2)-weighted magnetic resonance imaging at 9.4 T enables detection of cortical grey matter lesion in post-mortem multiple sclerosis brain. The quantitative associations suggest that in cortical grey matter T(1) may be a predictor of neuronal density, and T(2) of myelin content (and-secondarily-axons). Successful translation of these results into in vivo studies using high field magnetic resonance imaging (e.g. 3 T and 7 T) will improve the assessment of cortical pathology and thereby have an impact on the diagnosis and natural history studies of patients with multiple sclerosis, as well as clinical trial designs for putative treatments to prevent cortical demyelination and neuronal loss.

  17. Sparse and powerful cortical spikes.

    PubMed

    Wolfe, Jason; Houweling, Arthur R; Brecht, Michael

    2010-06-01

    Activity in cortical networks is heterogeneous, sparse and often precisely timed. The functional significance of sparseness and precise spike timing is debated, but our understanding of the developmental and synaptic mechanisms that shape neuronal discharge patterns has improved. Evidence for highly specialized, selective and abstract cortical response properties is accumulating. Singe-cell stimulation experiments demonstrate a high sensitivity of cortical networks to the action potentials of some, but not all, single neurons. It is unclear how this sensitivity of cortical networks to small perturbations comes about and whether it is a generic property of cortex. The unforeseen sensitivity to cortical spikes puts serious constraints on the nature of neural coding schemes.

  18. High-Resolution fMRI Maps of Cortical Activation in Nonhuman Primates: Correlation with Intrinsic Signal Optical Images

    PubMed Central

    Roe, Anna W.; Chen, Li Min

    2009-01-01

    One of the most widely used functional brain mapping tools is blood oxygen level–dependent (BOLD) functional magnetic resonance imaging (fMRI). This method has contributed to new understandings of the functional roles of different areas in the human brain. However, its ability to map cerebral cortex at high spatial (submillimeter) resolution is still unknown. Other methods such as single- and multiunit electrophysiology and intrinsic signal optical imaging have revealed submillimeter resolution of sensory topography and cortical columnar activations. However, they are limited either by spatial scale (electrophysiology characterizes only local groups of neurons) or by the inability to monitor deep structures in the brain (i.e., cortical regions buried in sulci or subcortical structures). A method that could monitor all regions of the brain at high spatial resolution would be ideal. This capacity would open the doors to investigating, for example, how networks of cerebral cortical columns relate to or produce behavior. In this article we demonstrate that, without benefit of contrast agents, at a magnetic field strength of 9.4 tesla, BOLD fMRI can reveal millimeter-sized topographic maps of digit representation in the somatosensory cortex of the anesthetized squirrel monkey. Furthermore, by mapping the “funneling illusion,” it is possible to detect even submillimeter shifts in activation in the cortex. Our data suggest that at high magnetic field strength, the positive BOLD signal can be used to reveal high spatial resolution maps of brain activity, a finding that weakens previous notions about the ultimate spatial specificity of the positive BOLD signal. PMID:18172338

  19. High-resolution coherent backscatter interferometric radar images of equatorial spread F using Capon's method

    NASA Astrophysics Data System (ADS)

    Rodrigues, Fabiano S.; de Paula, Eurico R.; Zewdie, Gebreab K.

    2017-03-01

    We present results of Capon's method for estimation of in-beam images of ionospheric scattering structures observed by a small, low-power coherent backscatter interferometer. The radar interferometer operated in the equatorial site of São Luís, Brazil (2.59° S, 44.21° W, -2.35° dip latitude). We show numerical simulations that evaluate the performance of the Capon method for typical F region measurement conditions. Numerical simulations show that, despite the short baselines of the São Luís radar, the Capon technique is capable of distinguishing localized features with kilometric scale sizes (in the zonal direction) at F region heights. Following the simulations, we applied the Capon algorithm to actual measurements made by the São Luís interferometer during a typical equatorial spread F (ESF) event. As indicated by the simulations, the Capon method produced images that were better resolved than those produced by the Fourier method. The Capon images show narrow (a few kilometers wide) scattering channels associated with ESF plumes and scattering regions spaced by only a few tens of kilometers in the zonal direction. The images are also capable of resolving bifurcations and the C shape of scattering structures.

  20. Direct imaging with highly diluted apertures - II. Properties of the point spread function of a hypertelescope

    NASA Astrophysics Data System (ADS)

    Patru, F.; Tarmoul, N.; Mourard, D.; Lardière, O.

    2009-06-01

    In the future, optical stellar interferometers will provide true images thanks to larger number of telescopes and to advanced cophasing subsystems. These conditions are required to have sufficient resolution elements (resel) in the image and to provide direct images in the hypertelescope mode. It has already been shown that hypertelescopes provide snapshot images with a significant gain in sensitivity without inducing any loss of the useful field of view for direct imaging applications. This paper aims at studying the properties of the point spread functions of future large arrays using the hypertelescope mode. Numerical simulations have been performed and criteria have been defined to study the image properties. It is shown that the choice of the configuration of the array is a trade-off between the resolution, the halo level and the field of view. A regular pattern of the array of telescopes optimizes the image quality (low halo level and maximum encircled energy in the central peak), but decreases the useful field of view. Moreover, a non-redundant array is less sensitive to the space aliasing effect than a redundant array.

  1. Cortical somatosensory evoked high-frequency (600Hz) oscillations predict absence of severe hypoxic encephalopathy after resuscitation.

    PubMed

    Endisch, Christian; Waterstraat, Gunnar; Storm, Christian; Ploner, Christoph J; Curio, Gabriel; Leithner, Christoph

    2016-07-01

    Following cardiac arrest (CA), hypoxic encephalopathy (HE) frequently occurs and hence reliable neuroprognostication is crucial to decide on the extent of intensive care. Several investigations predict severe HE leading to persistent unresponsive wakefulness or death, with high specificity. Only few studies attempted to predict absence of severe HE. Cortical somatosensory evoked high-frequency (600Hz) oscillation (HFO) bursts indicate the presence of highly synchronized spiking activity in the primary somatosensory cortex. Since global neuronal damage characterizes severe HE preserved cortical HFOs may early exclude severe HE. We determined amplitudes of early and late HFO bursts in 302 comatose CA patients after median nerve somatosensory evoked potential (SSEPs) and clinical outcome upon intensive care unit discharge using the cerebral performance category (CPC) scale. We detected significant early HFO bursts in 146 patients and late HFO bursts in 95 patients. Only one of 27 unresponsive wakefulness patients had a late HFO burst amplitude above 70nV and all seventeen patients who died despite higher amplitudes died from non-neurological causes. High-frequency SSEP components can reliably be studied in comatose CA patients using standard equipment. Late HFO burst amplitudes above 70nV largely exclude severe HE incompatible with regaining consciousness. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Cortico-cortical communication dynamics

    PubMed Central

    Roland, Per E.; Hilgetag, Claus C.; Deco, Gustavo

    2014-01-01

    In principle, cortico-cortical communication dynamics is simple: neurons in one cortical area communicate by sending action potentials that release glutamate and excite their target neurons in other cortical areas. In practice, knowledge about cortico-cortical communication dynamics is minute. One reason is that no current technique can capture the fast spatio-temporal cortico-cortical evolution of action potential transmission and membrane conductances with sufficient spatial resolution. A combination of optogenetics and monosynaptic tracing with virus can reveal the spatio-temporal cortico-cortical dynamics of specific neurons and their targets, but does not reveal how the dynamics evolves under natural conditions. Spontaneous ongoing action potentials also spread across cortical areas and are difficult to separate from structured evoked and intrinsic brain activity such as thinking. At a certain state of evolution, the dynamics may engage larger populations of neurons to drive the brain to decisions, percepts and behaviors. For example, successfully evolving dynamics to sensory transients can appear at the mesoscopic scale revealing how the transient is perceived. As a consequence of these methodological and conceptual difficulties, studies in this field comprise a wide range of computational models, large-scale measurements (e.g., by MEG, EEG), and a combination of invasive measurements in animal experiments. Further obstacles and challenges of studying cortico-cortical communication dynamics are outlined in this critical review. PMID:24847217

  3. Measurements of Doppler and multipath spread on oblique high-latitude HF paths and their use in characterizing data modem performance

    NASA Astrophysics Data System (ADS)

    Angling, Matthew J.; Cannon, Paul S.; Davies, Nigel C.; Willink, Tricia J.; Jodalen, Vivianne; Lundborg, Bengt

    1998-01-01

    Measurements of Doppler spread, multipath spread, and signal-to-noise ratio have been made on four high-latitude high-frequency (HF) communications paths. The measurement system and analysis techniques are outlined, and an analysis of the data pertinent to the design of robust HF data modems is presented. A summary of the spreads that are exceeded for 5% of time is presented for each path. Doppler spreads range from 2 to 55 Hz, while multipath spreads range from 1 to 11 ms. Physical interpretations of the data are made, and the data are related to the measured performance characteristics of an HF data modem to estimate the modem availability on the paths considered. When there is mode support, availabilities range from 64% to 100% for a signal-to-noise ratio of 0 dB, although the data indicate that the availabilities can generally be increased by optimizing frequency selection.

  4. High-level expression of alternative oxidase protein sequences enhances the spread of viral vectors in resistant and susceptible plants.

    PubMed

    Murphy, Alex M; Gilliland, Androulla; York, Caroline J; Hyman, Belinda; Carr, John P

    2004-12-01

    The alternative oxidase (AOX) is the terminal oxidase of the cyanide-resistant alternative respiratory pathway in plants and has been implicated in resistance to viruses. When tobacco mosaic virus (TMV) vectors were used to drive very high levels of expression of either AOX or AOX mutated in its active site (AOX-E), virus spread was enhanced. This was visualized as the induction of larger hypersensitive-response lesions after inoculation onto NN-genotype tobacco than those produced by vectors bearing sequences of comparable length [the green fluorescent protein (gfp) gene sequence or antisense aox] or the 'empty' viral vector. Also, in the highly susceptible host Nicotiana benthamiana, systemic movement of TMV vectors expressing AOX or AOX-E was faster than that of TMV constructs bearing gfp or antisense aox sequences. Notably, in N. benthamiana, TMV.AOX and TMV.AOX-E induced symptoms that were severe and ultimately included cell death, whereas the empty vector, TMV.GFP and the TMV vector expressing antisense aox sequences never induced necrosis. The results show that, if expressed at sufficiently high levels, active and inactive AOX proteins can affect virus spread and symptomology in plants.

  5. Mental rotation studied by functional magnetic resonance imaging at high field (4 tesla): performance and cortical activation.

    PubMed

    Tagaris, G A; Kim, S G; Strupp, J P; Andersen, P; Uğurbil, K; Georgopoulos, A P

    1997-07-01

    We studied the performance and cortical activation patterns during a mental rotation task (Shepard & Metzler, 1971) using functional magnetic resonance imaging (fMlU) at high field (4 Tesla). Twenty-four human subjects were imaged (fMRI group), whereas six additional subjects performed the task without being imaged (control group). All subjects were shown pairs of perspective drawings of 31, objects and asked to judge whether they were the same or mirror images. The measures of performance examined included (1) the percentage of errors, (2) the speed of performance, calculated as the inverse of the average response time, and (3) the rate of rotation for those object pairs correctly identified as "same." We found the following: (1) Subjects in the fMRI group performed well outside and inside the magnet, and, in the latter case, before and during data acquisition. Moreover, performance over time improved in the same manner as in the control group. These findings indicate that exposure to high magnetic fields does not impair performance in mental rotation. (2) Functional activation data were analyzed from 16 subjects of the fMRI goup. Several cortical areas were activated during task performance. The relations between the measures of performance above and the magnitude of activation of specific cortical areas were investigated by anatomically demarcating these areas of interest and calculating a normalized activation for each one of them. (3) We used the multivariate technique of hierarchical tree modeling to determine functional clustering among areas of interest and performance measures. Two main branches were distinguished: One comprised areas in the right hemisphere and the extrastriate and superior parietal lobules bilaterally, whereas the other comprised areas of the left hemisphere and the frontal pole bilaterally; all three performance measures above clustered with the former branch. Specifically, performance outcome ("percentage of errors") clustered with the

  6. Practices associated with Highly Pathogenic Avian Influenza spread in traditional poultry marketing chains: Social and economic perspectives.

    PubMed

    Paul, Mathilde; Baritaux, Virginie; Wongnarkpet, Sirichai; Poolkhet, Chaithep; Thanapongtharm, Weerapong; Roger, François; Bonnet, Pascal; Ducrot, Christian

    2013-04-01

    In developing countries, smallholder poultry production contributes to food security and poverty alleviation in rural areas. However, traditional poultry marketing chains have been threatened by the epidemics caused by the Highly Pathogenic Avian Influenza (H5N1) virus. The article presents a value chain analysis conducted on the traditional poultry marketing chain in the rural province of Phitsanulok, Thailand. The analysis is based on quantitative data collected on 470 backyard chicken farms, and on qualitative data collected on 28 poultry collectors, slaughterhouses and market retailers, using semi-structured interviews. The article examines the organization of poultry marketing chains in time and space, and shows how this may contribute to the spread of Highly Pathogenic Avian Influenza H5N1 in the small-scale poultry sector. The article also discusses the practices and strategies developed by value chain actors facing poultry mortality, with their economic and social determinants. More broadly, this study also illustrates how value chain analysis can contribute to a better understanding of the complex mechanisms associated with the spread of epidemics in rural communities. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. The Effect of Noscapine on Oxygen-Glucose Deprivation on Primary Murine Cortical Neurons in High Glucose Condition.

    PubMed

    Vahabzadeh, Gelareh; Ebrahimi, Soltan-Ahmed; Rahbar-Roshandel, Nahid; Mahmoudian, Massoud

    2016-01-01

    In the present work we set out to investigate the neuroprotective effects of noscapine (0.5-2 µM) in presence of D-glucose on primary murine foetal cortical neurons after oxygen-glucose deprivation/24 h. recovery. Cell viability, nitric oxide production and intracellular calcium ((ca(2+))i) levels were evaluated by MTT assay, the modified Griess method and Fura-2 respectively. 25 and 100 mM D-glucose could, in a concentration dependent manner, improve cell viability and decrease NO production and (ca(2+))i level in neuronal cells after ischemic insult. Moreover, pre-incubation of cells with noscapine, noticeably enhanced protective effects of 25 and 100 mM D-glucose compared to similar conditions without noscapine pre-treatment. In fact, noscapine attenuated NO production in a dose-dependent fashion, after 30 minutes (min) OGD, during high-glucose (HG) condition in cortical neurons. Pretreatment with 2 μM noscapine and 25 or 100 mM D-glucose, was shown to decrease the rise in (ca(2+))i induced by Sodium azide/glucose deprivation (chemical OGD) model. These effects were more pronounced than that of 25 or 100 mM D-glucose alone. The present study demonstrated that the neuroprotective effects of HG before an ischemic insult were augmented by pre-treatment with noscapine. Our results also suggested that the neuroprotection offered by both HG and noscapine involve attenuation of NO production and (ca(2+))i levels stimulated by the experimental ischemia in cortical neurons.

  8. The Effect of Noscapine on Oxygen-Glucose Deprivation on Primary Murine Cortical Neurons in High Glucose Condition

    PubMed Central

    Vahabzadeh, Gelareh; Ebrahimi, Soltan-Ahmed; Rahbar-Roshandel, Nahid; Mahmoudian, Massoud

    2016-01-01

    In the present work we set out to investigate the neuroprotective effects of noscapine (0.5-2 µM) in presence of D-glucose on primary murine foetal cortical neurons after oxygen–glucose deprivation/24 h. recovery. Cell viability, nitric oxide production and intracellular calcium ((ca2+)i) levels were evaluated by MTT assay, the modified Griess method and Fura-2 respectively. 25 and 100 mM D-glucose could, in a concentration dependent manner, improve cell viability and decrease NO production and (ca2+)i level in neuronal cells after ischemic insult. Moreover, pre-incubation of cells with noscapine, noticeably enhanced protective effects of 25 and 100 mM D-glucose compared to similar conditions without noscapine pre-treatment. In fact, noscapine attenuated NO production in a dose-dependent fashion, after 30 minutes (min) OGD, during high-glucose (HG) condition in cortical neurons. Pretreatment with 2 μM noscapine and 25 or 100 mM D-glucose, was shown to decrease the rise in (ca2+)i induced by Sodium azide/glucose deprivation (chemical OGD) model. These effects were more pronounced than that of 25 or 100 mM D-glucose alone. The present study demonstrated that the neuroprotective effects of HG before an ischemic insult were augmented by pre-treatment with noscapine. Our results also suggested that the neuroprotection offered by both HG and noscapine involve attenuation of NO production and (ca2+)i levels stimulated by the experimental ischemia in cortical neurons. PMID:27642321

  9. Exposure to high glutamate concentration activates aerobic glycolysis but inhibits ATP-linked respiration in cultured cortical astrocytes.

    PubMed

    Shen, Yao; Tian, Yueyang; Shi, Xiaojie; Yang, Jianbo; Ouyang, Li; Gao, Jieqiong; Lu, Jianxin

    2014-08-01

    Astrocytes play a key role in removing the synaptically released glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. However, high concentration of glutamate leads to toxicity in astrocytes, and the underlying mechanisms are unclear. The purpose of this study was to investigate whether energy metabolism disorder, especially impairment of mitochondrial respiration, is involved in the glutamate-induced gliotoxicity. Exposure to 10-mM glutamate for 48 h stimulated glycolysis and respiration in astrocytes. However, the increased oxygen consumption was used for proton leak and non-mitochondrial respiration, but not for oxidative phosphorylation and ATP generation. When the exposure time extended to 72 h, glycolysis was still activated for ATP generation, but the mitochondrial ATP-linked respiration of astrocytes was reduced. The glutamate-induced astrocyte damage can be mimicked by the non-metabolized substrate d-aspartate but reversed by the non-selective glutamate transporter inhibitor TBOA. In addition, the glutamate toxicity can be partially reversed by vitamin E. These findings demonstrate that changes of bioenergetic profile occur in cultured cortical astrocytes exposed to high concentration of glutamate and highlight the role of mitochondria respiration in glutamate-induced gliotoxicity in cortical astrocytes.

  10. High-Resolution fMRI of Auditory Cortical Map Changes in Unilateral Hearing Loss and Tinnitus.

    PubMed

    Ghazaleh, Naghmeh; Zwaag, Wietske van der; Clarke, Stephanie; Ville, Dimitri Van De; Maire, Raphael; Saenz, Melissa

    2017-02-06

    Animal models of hearing loss and tinnitus observe pathological neural activity in the tonotopic frequency maps of the primary auditory cortex. Here, we applied ultra high-field fMRI at 7 T to test whether human patients with unilateral hearing loss and tinnitus also show altered functional activity in the primary auditory cortex. The high spatial resolution afforded by 7 T imaging allowed tonotopic mapping of primary auditory cortex on an individual subject basis. Eleven patients with unilateral hearing loss and tinnitus were compared to normal-hearing controls. Patients showed an over-representation and hyperactivity in a region of the cortical map corresponding to low frequencies sounds, irrespective of the hearing loss and tinnitus range, which in most cases affected higher frequencies. This finding of hyperactivity in low frequency map regions, irrespective of hearing loss range, is consistent with some previous studies in animal models and corroborates a previous study of human tinnitus. Thus these findings contribute to accumulating evidence that gross cortical tonotopic map reorganization is not a causal factor of tinnitus.

  11. Afferent inputs to cortical fast-spiking interneurons organize pyramidal cell network oscillations at high-gamma frequencies (60–200 Hz)

    PubMed Central

    Crone, Nathan E.; Franaszczuk, Piotr J.

    2014-01-01

    High-gamma activity, ranging in frequency between ∼60 Hz and 200 Hz, has been observed in local field potential, electrocorticography, EEG and magnetoencephalography signals during cortical activation, in a variety of functional brain systems. The origin of these signals is yet unknown. Using computational modeling, we show that a cortical network model receiving thalamic input generates high-gamma responses comparable to those observed in local field potential recorded in monkey somatosensory cortex during vibrotactile stimulation. These high-gamma oscillations appear to be mediated mostly by an excited population of inhibitory fast-spiking interneurons firing at high-gamma frequencies and pacing excitatory regular-spiking pyramidal cells, which fire at lower rates but in phase with the population rhythm. The physiological correlates of high-gamma activity, in this model of local cortical circuits, appear to be similar to those proposed for hippocampal ripples generated by subsets of interneurons that regulate the discharge of principal cells. PMID:25210164

  12. The "inherent vice" in the anti-angiogenic theory may cause the highly metastatic cancer to spread more aggressively.

    PubMed

    Wang, Denian; Tan, Chun; Xiao, Fei; Zou, Lan; Wang, Lijun; Wei, Yong'gang; Yang, Hanshuo; Zhang, Wei

    2017-05-24

    Although anti-angiogenic (AA) therapy is widely used in clinical practice, it is often challenged by insufficient efficacy and intrinsic resistance. Some studies have reported that AA therapy can even increase tumor metastasis. However, whether this is due to a specific AA drug causing a specific tumor to metastasize or because the anti-angiogenic theory has some "inherent vice" that may inevitably lead to tumor dissemination remains a mystery. Herein, we designed a model that completely blocks tumor blood supply using a physical barrier to examine tumor behavior in such circumstances. Surprisingly, we found that cutting off the blood supply could neither eliminate the primary tumor cells nor prevent local invasion or formation of distant metastases. By using a mathematical method to simulate tumor behavior, we found that blocking tumor blood supply may lead to an inevitable consequence: the cells that can tolerate blood deficiency are "naturally selected" and survive, whereas a portion of cells are promoted to escape from the "starvation" area by the consistent environmental stress until they are spread throughout the body. This may be an intrinsic disadvantage of the AA strategy, which will inevitably cause the tumor, particularly highly metastatic tumors, to spread more aggressively.

  13. Effects on axial momentum spread on the electron-ion two-stream instability in high-intensity ion beams

    SciTech Connect

    R. Davidso; H. Qin

    2000-06-15

    Use is made of the Vlasov-Maxwell equations to describe the electron-ion two-stream instability driven by the directed axial motion of a high-intensity ion beam propagating through a stationary population of (unwanted) background electrons. The ion beam is treated as continuous in the z-direction, and the electrons are electrostatically confined in the transverse direction by the space-charge potential produced by the excession charge. The analysis is carried out for arbitrary beam intensity, consistent with transverse confinement of the beam particles, and arbitrary fractional charge neutralization by the background electrons. For the case of overlapping step-function ion and electron density profiles, corresponding to monoenergetic electrons and ions in the transverse direction, detailed stability properties are calculated, including the important effects of an axial momentum spread, over a wide range of system parameters for dipole perturbations with azimuthal mode number l=1. The two-stream instability growth rate is found to increase with increasing beam intensity, increasing fractional charge neutralization, and decreasing proximity of the conducting wall. It is shown that Landau damping associated with a modest axial momentum spread of the beam ions and background electrons has a strong stabilizing influence on the instability.

  14. An annular high-current electron beam with an energy spread in a coaxial magnetically insulated diode

    SciTech Connect

    Grishkov, A. A. Pegel, I. V.

    2013-11-15

    An elementary theory of an annular high-current electron beam in a uniform transport channel and a coaxial magnetically insulated diode is generalized to the case of counterpropagating electron beams with a spread over kinetic energies. Expressions for the sum of the absolute values of the forward and backward currents in a uniform transport channel and for the flux of the longitudinal component of the generalized momentum in a coaxial magnetically insulated diode as functions of the maximum electron kinetic energy are derived for different values of the relative width of the energy distribution function. It is shown that, in a diode with an expanding transport channel and a virtual cathode limiting the extracted current, counterpropagating particle flows are established between the cathode and the virtual cathode within a certain time interval after the beginning of electron emission. The accumulation of electrons in these flows is accompanied by an increase in their spread over kinetic energies and the simultaneous decrease in the maximum kinetic energy. The developed model agrees with the results of particle-in-cell simulations performed using the KARAT and OOPIC-Pro codes.

  15. Differentiation from human pluripotent stem cells of cortical neurons of the superficial layers amenable to psychiatric disease modeling and high-throughput drug screening

    PubMed Central

    Boissart, C; Poulet, A; Georges, P; Darville, H; Julita, E; Delorme, R; Bourgeron, T; Peschanski, M; Benchoua, A

    2013-01-01

    Cortical neurons of the superficial layers (II-IV) represent a pivotal neuronal population involved in the higher cognitive functions of the human and are particularly affected by psychiatric diseases with developmental manifestations such as schizophrenia and autism. Differentiation protocols of human pluripotent stem cells (PSC) into cortical neurons have been achieved, opening the way to in vitro modeling of neuropsychiatric diseases. However, these protocols commonly result in the asynchronous production of neurons typical for the different layers of the cortex within an extended period of culture, thus precluding the analysis of specific subtypes of neurons in a standardized manner. Addressing this issue, we have successfully captured a stable population of self-renewing late cortical progenitors (LCPs) that synchronously and massively differentiate into glutamatergic cortical neurons of the upper layers. The short time course of differentiation into neurons of these progenitors has made them amenable to high-throughput assays. This has allowed us to analyze the capability of LCPs at differentiating into post mitotic neurons as well as extending and branching neurites in response to a collection of selected bioactive molecules. LCPs and cortical neurons of the upper layers were successfully produced from patient-derived-induced PSC, indicating that this system enables functional studies of individual-specific cortical neurons ex vivo for disease modeling and therapeutic purposes. PMID:23962924

  16. Genesis and Spread of Newly Emerged Highly Pathogenic H7N9 Avian Viruses in Mainland China.

    PubMed

    Yang, Lei; Zhu, Wenfei; Li, Xiyan; Chen, Minmei; Wu, Jie; Yu, Pengbo; Qi, Shunxiang; Huang, Yiwei; Shi, Weixian; Dong, Jie; Zhao, Xiang; Huang, Weijuan; Li, Zi; Zeng, Xiaoxu; Bo, Hong; Chen, Tao; Chen, Wenbing; Liu, Jia; Zhang, Ye; Liang, Zhenli; Shi, Wei; Shu, Yuelong; Wang, Dayan

    2017-09-27

    The novel low pathogenic H7N9 avian influenza A viruses (LPAI H7N9) have caused a threat to public health for their high mortality and morbidity since their emergence in 2013. Recently, highly pathogenic variants of these H7N9 viruses (HPAI H7N9) have emerged and caused human infections and poultry outbreaks in Mainland China. However, it is still unclear how the HPAI H7N9 virus was generated and how it evolved and spread in China. Here, we show that the ancestor virus of the HPAI H7N9 viruses originated in the Yangtze Delta Region and spread southward to the Pearl Delta Region, possibly through live poultry trades. After introduction into the Pearl Delta Region, the origin LPAI H7N9 virus acquired four amino acid insertions in the HA protein cleavage site and mutated into the HPAI H7N9 virus in late May 2016. Afterward, the HPAI H7N9 viruses further reassorted with LPAI H7N9 or H9N2 viruses locally and generated multiple different genotypes. As of 14 July 2017, the HAPI H7N9 viruses had spread from Guangdong province to at least 12 provinces. The rapid geographical expansion and genetic evolution of the HPAI H7N9 viruses pose a great challenge, not only to public health, but also to poultry production. Effective control measures, including enhanced surveillance, are therefore urgently needed.IMPORTANCE The LPAI H7N9 virus has caused five outbreak waves in humans and was recently reported to have mutated into highly pathogenic variants. It is unknown how the HPAI H7N9 virus originated, evolved, and disseminated in China. In this study, we comprehensively analyzed the sequences of HPAI H7N9 viruses from 28 human and 21 environmental samples covering eight provinces in China that were taken from November 2016 to June 2017. The results show that the ancestor virus of the HPAI H7N9 viruses originated in the Yangtze Delta Region. However, the insertion event of four amino acids in the HA protein cleavage site of a LPAI H7N9 virus occurred in late May 2016, in the Pearl

  17. Estimation of the effective and functional human cortical connectivity with structural equation modeling and directed transfer function applied to high-resolution EEG.

    PubMed

    Astolfi, Laura; Cincotti, Febo; Mattia, Donatella; Salinari, Serenella; Babiloni, Claudio; Basilisco, Alessandra; Rossini, Paolo Maria; Ding, Lei; Ni, Ying; He, Bin; Marciani, Maria Grazia; Babiloni, Fabio

    2004-12-01

    Different brain imaging devices are presently available to provide images of the human functional cortical activity, based on hemodynamic, metabolic or electromagnetic measurements. However, static images of brain regions activated during particular tasks do not convey the information of how these regions are interconnected. The concept of brain connectivity plays a central role in the neuroscience, and different definitions of connectivity, functional and effective, have been adopted in literature. While the functional connectivity is defined as the temporal coherence among the activities of different brain areas, the effective connectivity is defined as the simplest brain circuit that would produce the same temporal relationship as observed experimentally among cortical sites. The structural equation modeling (SEM) is the most used method to estimate effective connectivity in neuroscience, and its typical application is on data related to brain hemodynamic behavior tested by functional magnetic resonance imaging (fMRI), whereas the directed transfer function (DTF) method is a frequency-domain approach based on both a multivariate autoregressive (MVAR) modeling of time series and on the concept of Granger causality. This study presents advanced methods for the estimation of cortical connectivity by applying SEM and DTF on the cortical signals estimated from high-resolution electroencephalography (EEG) recordings, since these signals exhibit a higher spatial resolution than conventional cerebral electromagnetic measures. To estimate correctly the cortical signals, we used a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from individual MRI, a distributed source model and a regularized linear inverse source estimates of cortical current density. Before the application of SEM and DTF methodology to the cortical waveforms estimated from high-resolution EEG data, we performed a simulation study, in which different main factors

  18. Fighting High School Senior Slump: The Spread of an Alternative Senior Program.

    ERIC Educational Resources Information Center

    Wade, Taron

    1999-01-01

    At several New York State high schools, seniors hold internships in architectural firms, Planned Parenthood, dentists' offices, and television and radio stations. Some make documentaries or pursue independent study in various subjects. These opportunities arise through a program (WISE) allowing second-semester seniors to design and complete their…

  19. High Speed Cinematography of Cracks Spreading under Failure of Amorphous Metallic Alloys

    NASA Astrophysics Data System (ADS)

    Tabachnikova, Elena

    2000-03-01

    Amorphous metallic alloys are unique high strength materials that under low temperature straining (300 - 77 K) are absolutely thermomechanically unstable against the catastrophic plastic shear. Its velocity is close to the transverse sound velocity ct. That is why experimental studying of shear crack propagation in amorphous alloy ribbons at low temperatures needs high-speed methods of observations. Samples of the NI78Si8B14 and Fe70Ni10B20 amorphous alloys ribbons were tensile tested in a pulse testing mashine. The motion of the main crack front during ductile shear failure was studied by means of a high-speed film camera (SFR-2M) with a frame frequency of 2x106 s-1. Loading of the sample was synchronized with both the pulse light source and the high-speed camera. Results of observations: a) the velocity of of shear crack propagation is close to the maximum theoretical limit 0.9 ct; b) a pulsating motion of of the crack is observed with a retardation of crack motion at the moment of branching or changing the orientation of the crack surface that became faceted; the process of shear crack propagation is step-like.

  20. Spread of a New Parasitic B Chromosome Variant Is Facilitated by High Gene Flow

    PubMed Central

    Manrique-Poyato, María Inmaculada; López-León, María Dolores; Cabrero, Josefa; Perfectti, Francisco; Camacho, Juan Pedro M.

    2013-01-01

    The B24 chromosome variant emerged several decades ago in a Spanish population of the grasshopper Eyprepocnemis plorans and is currently reaching adjacent populations. Here we report, for the first time, how a parasitic B chromosome (a strictly vertically transmitted parasite) expands its geographical range aided by high gene flow in the host species. For six years we analyzed B frequency in several populations to the east and west of the original population and found extensive spatial variation, but only a slight temporal trend. The highest B24 frequency was found in its original population (Torrox) and it decreased closer to both the eastern and the western populations. The analysis of Inter Simple Sequence Repeat (ISSR) markers showed the existence of a low but significant degree of population subdivision, as well as significant isolation by distance (IBD). Pairwise Nem estimates suggested the existence of high gene flow between the four populations located in the Torrox area, with higher values towards the east. No significant barriers to gene flow were found among these four populations, and we conclude that high gene flow is facilitating B24 diffusion both eastward and westward, with minor role for B24 drive due to the arrival of drive suppressor genes which are also frequent in the donor population. PMID:24386259

  1. Spread of a new parasitic B chromosome variant is facilitated by high gene flow.

    PubMed

    Manrique-Poyato, María Inmaculada; López-León, María Dolores; Cabrero, Josefa; Perfectti, Francisco; Camacho, Juan Pedro M

    2013-01-01

    The B24 chromosome variant emerged several decades ago in a Spanish population of the grasshopper Eyprepocnemis plorans and is currently reaching adjacent populations. Here we report, for the first time, how a parasitic B chromosome (a strictly vertically transmitted parasite) expands its geographical range aided by high gene flow in the host species. For six years we analyzed B frequency in several populations to the east and west of the original population and found extensive spatial variation, but only a slight temporal trend. The highest B24 frequency was found in its original population (Torrox) and it decreased closer to both the eastern and the western populations. The analysis of Inter Simple Sequence Repeat (ISSR) markers showed the existence of a low but significant degree of population subdivision, as well as significant isolation by distance (IBD). Pairwise Nem estimates suggested the existence of high gene flow between the four populations located in the Torrox area, with higher values towards the east. No significant barriers to gene flow were found among these four populations, and we conclude that high gene flow is facilitating B24 diffusion both eastward and westward, with minor role for B24 drive due to the arrival of drive suppressor genes which are also frequent in the donor population.

  2. Rapid spread of the defensive endosymbiont Spiroplasma in Drosophila hydei under high parasitoid wasp pressure.

    PubMed

    Xie, Jialei; Winter, Caitlyn; Winter, Lauryn; Mateos, Mariana

    2015-02-01

    Maternally transmitted endosymbionts of insects are ubiquitous in nature and play diverse roles in the ecology and evolution of their hosts. To persist in host lineages, many symbionts manipulate host reproduction to their advantage (e.g. cytoplasmic incompatibility and male-killing), or confer fitness benefits to their hosts (e.g. metabolic provisioning and defense against natural enemies). Recent studies suggest that strains of the bacterial genus Spiroplasma protect their host (flies in the genus Drosophila) against parasitoid attack. The Spiroplasma-conferred protection is partial and flies surviving a wasp attack have reduced adult longevity and fecundity. Therefore, it is unclear whether protection against wasps alone can counter Spiroplasma loss by imperfect maternal transmission and any possible fitness costs to harboring Spiroplasma. To address this question, we conducted a population cage study comparing Spiroplasma frequencies over time (host generations) under conditions of high wasp pressure and no wasp pressure. A dramatic increase of Spiroplasma prevalence was observed under high wasp pressure. In contrast, Spiroplasma prevalence in the absence of wasps did not change significantly over time; a pattern consistent with random drift. Thus, the defensive mechanism may contribute to the high prevalence of Spiroplasma in host populations despite imperfect vertical transmission. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Visual recovery in cortical blindness is limited by high internal noise

    PubMed Central

    Cavanaugh, Matthew R.; Zhang, Ruyuan; Melnick, Michael D.; Das, Anasuya; Roberts, Mariel; Tadin, Duje; Carrasco, Marisa; Huxlin, Krystel R.

    2015-01-01

    Damage to the primary visual cortex typically causes cortical blindness (CB) in the hemifield contralateral to the damaged hemisphere. Recent evidence indicates that visual training can partially reverse CB at trained locations. Whereas training induces near-complete recovery of coarse direction and orientation discriminations, deficits in fine motion processing remain. Here, we systematically disentangle components of the perceptual inefficiencies present in CB fields before and after coarse direction discrimination training. In seven human CB subjects, we measured threshold versus noise functions before and after coarse direction discrimination training in the blind field and at corresponding intact field locations. Threshold versus noise functions were analyzed within the framework of the linear amplifier model and the perceptual template model. Linear amplifier model analysis identified internal noise as a key factor differentiating motion processing across the tested areas, with visual training reducing internal noise in the blind field. Differences in internal noise also explained residual perceptual deficits at retrained locations. These findings were confirmed with perceptual template model analysis, which further revealed that the major residual deficits between retrained and intact field locations could be explained by differences in internal additive noise. There were no significant differences in multiplicative noise or the ability to process external noise. Together, these results highlight the critical role of altered internal noise processing in mediating training-induced visual recovery in CB fields, and may explain residual perceptual deficits relative to intact regions of the visual field. PMID:26389544

  4. An optimal point spread function subtraction algorithm for high-contrast imaging: a demonstration with angular differential imaging

    SciTech Connect

    Lafreniere, D; Marois, C; Doyon, R; Artigau, E; Nadeau, D

    2006-09-19

    Direct imaging of exoplanets is limited by bright quasi-static speckles in the point spread function (PSF) of the central star. This limitation can be reduced by subtraction of reference PSF images. We have developed an algorithm to construct an optimal reference PSF image from an arbitrary set of reference images. This image is built as a linear combination of all available images and is optimized independently inside multiple subsections of the image to ensure that the absolute minimum residual noise is achieved within each subsection. The algorithm developed is completely general and can be used with many high contrast imaging observing strategies, such as angular differential imaging (ADI), roll subtraction, spectral differential imaging, reference star observations, etc. The performance of the algorithm is demonstrated for ADI data. It is shown that for this type of data the new algorithm provides a gain in sensitivity by up 22 to a factor 3 at small separation over the algorithm previously used.

  5. Reproductive ratio for the local spread of highly pathogenic avian influenza in wild bird populations of Europe, 2005-2008.

    PubMed

    Iglesias, I; Perez, A M; Sánchez-Vizcaíno, J M; Muñoz, M J; Martínez, M; de la Torre, A

    2011-01-01

    Highly pathogenic avian influenza (HPAI) has devastating consequences for the poultry industry of affected countries. Control of HPAI has been impaired by the role of wildlife species that act as disease reservoirs and as a potential source of infection for domestic populations. The reproductive ratio (R₀) of HPAI was quantified in nine clusters of outbreaks detected in wild birds in Europe (2005-2008) for which population data were not available. The median value of R₀ was similar (1·1-3·4) for the nine clusters and it was about tenfold smaller than the value estimated for poultry in The Netherlands in 2003. Results presented here will be useful to parameterize models for spread of HPAI in wild birds and to design effective prevention programmes for the European poultry sector. The method is suitable to estimate R₀ in the absence of population data, which is a condition typically observed for many wildlife and certain domestic species and systems.

  6. Control of energy spread and dark current in proton and ion beams generated in high-contrast laser solid interactions.

    PubMed

    Dollar, F; Matsuoka, T; Petrov, G M; Thomas, A G R; Bulanov, S S; Chvykov, V; Davis, J; Kalinchenko, G; McGuffey, C; Willingale, L; Yanovsky, V; Maksimchuk, A; Krushelnick, K

    2011-08-05

    By using temporal pulse shaping of high-contrast, short pulse laser interactions with solid density targets at intensities of 2 × 10(21) W cm(-2) at a 45° incident angle, we show that it is possible to reproducibly generate quasimonoenergetic proton and ion energy spectra. The presence of a short pulse prepulse 33 ps prior to the main pulse produced proton spectra with an energy spread between 25% and 60% (ΔE/E) with energy of several MeV, with light ions becoming quasimonoenergetic for 50 nm targets. When the prepulse was removed, the energy spectra was broad. Numerical simulations suggest that expansion of the rear-side contaminant layer allowed for density conditions that prevented the protons from being screened from the sheath field, thus providing a low energy cutoff in the observed spectra normal to the target surface.

  7. Blacksmithing in a high-tech environment: ''Under the spreading CNC mill the laboratories' smithy stands''

    SciTech Connect

    Gunter, R.

    1987-04-22

    In some mass production processes, closed die forgings or drop forgings are applicable; however, the tooling costs and respective set-up times are generally quite high. Rarely does anyone in a prototype application ever think of heating a piece of stock to achieve thermally enhanced plasticity and then hand-hammering it on the anvil to form it to the desired shape. Yet at Sandia National Laboratories it has been found that a blacksmith shop complete with a coal fired forge, hammers, and anvil is a valuable asset, cost effective, and greatly enhances capabilities for producing prototype parts.

  8. High correlation of Middle East respiratory syndrome spread with Google search and Twitter trends in Korea.

    PubMed

    Shin, Soo-Yong; Seo, Dong-Woo; An, Jisun; Kwak, Haewoon; Kim, Sung-Han; Gwack, Jin; Jo, Min-Woo

    2016-09-06

    The Middle East respiratory syndrome coronavirus (MERS-CoV) was exported to Korea in 2015, resulting in a threat to neighboring nations. We evaluated the possibility of using a digital surveillance system based on web searches and social media data to monitor this MERS outbreak. We collected the number of daily laboratory-confirmed MERS cases and quarantined cases from May 11, 2015 to June 26, 2015 using the Korean government MERS portal. The daily trends observed via Google search and Twitter during the same time period were also ascertained using Google Trends and Topsy. Correlations among the data were then examined using Spearman correlation analysis. We found high correlations (>0.7) between Google search and Twitter results and the number of confirmed MERS cases for the previous three days using only four simple keywords: "MERS", " ("MERS (in Korean)"), " ("MERS symptoms (in Korean)"), and " ("MERS hospital (in Korean)"). Additionally, we found high correlations between the Google search and Twitter results and the number of quarantined cases using the above keywords. This study demonstrates the possibility of using a digital surveillance system to monitor the outbreak of MERS.

  9. High correlation of Middle East respiratory syndrome spread with Google search and Twitter trends in Korea

    PubMed Central

    Shin, Soo-Yong; Seo, Dong-Woo; An, Jisun; Kwak, Haewoon; Kim, Sung-Han; Gwack, Jin; Jo, Min-Woo

    2016-01-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV) was exported to Korea in 2015, resulting in a threat to neighboring nations. We evaluated the possibility of using a digital surveillance system based on web searches and social media data to monitor this MERS outbreak. We collected the number of daily laboratory-confirmed MERS cases and quarantined cases from May 11, 2015 to June 26, 2015 using the Korean government MERS portal. The daily trends observed via Google search and Twitter during the same time period were also ascertained using Google Trends and Topsy. Correlations among the data were then examined using Spearman correlation analysis. We found high correlations (>0.7) between Google search and Twitter results and the number of confirmed MERS cases for the previous three days using only four simple keywords: “MERS”, “” (“MERS (in Korean)”), “” (“MERS symptoms (in Korean)”), and “” (“MERS hospital (in Korean)”). Additionally, we found high correlations between the Google search and Twitter results and the number of quarantined cases using the above keywords. This study demonstrates the possibility of using a digital surveillance system to monitor the outbreak of MERS. PMID:27595921

  10. First Discovery and Investigation of a High-Temperature Hydrothermal Vent Field on the Ultra- Slow Spreading Southwest Indian Ridge

    NASA Astrophysics Data System (ADS)

    Tao, C.; Lin, J.; Guo, S.; Chen, Y. J.; Wu, G.; Han, X.; German, C. R.; Yoerger, D. R.; Zhu, J.; Zhou, N.; Su, X.; Baker, E. T.; Party, S.

    2007-12-01

    Two recent cruises on board the Chinese research vessel Dayang Yihao have successfully investigated the first active hydrothermal vent field to be located along the ultraslow spreading Southwest Indian Ridge (SWIR) and collected hydrothermal sulfide deposit samples. The newly discovered hydrothermal vent field is located on the western end of a magmatically robust spreading segment immediately west of the Gallieni transform fault. Preliminary evidence of strong turbidity anomalies was first measured during a Nov. 2005 cruise on board Dayang Yihao (InterRidge News, vol. 15, pp. 33-34, 2006). Color video footages of the seafloor in the vent-field area were first obtained by a deep-towed video camera in February 2007 during DY115-19 Leg 1, when significant water column turbidity anomalies, noticeable temperature anomalies and methane anomalies were also measured. The vent field was then precisely located, mapped, and photographed in great detail in February- March 2007 during the DY115-19 Leg 2, using the autonomous underwater vehicle ABE of the Woods Hole Oceanographic Institution. A high-resolution bathymetric map, more than 5,000 near-bottom color photos, and several types of water column data were all obtained during three phases of ABE dives. Within the approximately 120-m-long by 100-m-wide hydrothermal field, three groups of active high-temperature vents were identified and color images of black smokers and associated biological communities were obtained from ABE, flying 5 m above the seafloor. Hydrothermal sulfide deposits were then successfully obtained using a TV-guided grab.

  11. First Discovery and Investigation of a High-Temperature Hydrothermal Vent Field on the Ultra- Slow Spreading Southwest Indian Ridge

    NASA Astrophysics Data System (ADS)

    Tao, C.; Lin, J.; Guo, S.; Chen, Y. J.; Wu, G.; Han, X.; German, C. R.; Yoerger, D. R.; Zhu, J.; Zhou, N.; Su, X.; Baker, E. T.; Party, S.

    2004-12-01

    Two recent cruises on board the Chinese research vessel Dayang Yihao have successfully investigated the first active hydrothermal vent field to be located along the ultraslow spreading Southwest Indian Ridge (SWIR) and collected hydrothermal sulfide deposit samples. The newly discovered hydrothermal vent field is located on the western end of a magmatically robust spreading segment immediately west of the Gallieni transform fault. Preliminary evidence of strong turbidity anomalies was first measured during a Nov. 2005 cruise on board Dayang Yihao (InterRidge News, vol. 15, pp. 33-34, 2006). Color video footages of the seafloor in the vent-field area were first obtained by a deep-towed video camera in February 2007 during DY115-19 Leg 1, when significant water column turbidity anomalies, noticeable temperature anomalies and methane anomalies were also measured. The vent field was then precisely located, mapped, and photographed in great detail in February- March 2007 during the DY115-19 Leg 2, using the autonomous underwater vehicle ABE of the Woods Hole Oceanographic Institution. A high-resolution bathymetric map, more than 5,000 near-bottom color photos, and several types of water column data were all obtained during three phases of ABE dives. Within the approximately 120-m-long by 100-m-wide hydrothermal field, three groups of active high-temperature vents were identified and color images of black smokers and associated biological communities were obtained from ABE, flying 5 m above the seafloor. Hydrothermal sulfide deposits were then successfully obtained using a TV-guided grab.

  12. Identifying Highly Connected Counties Compensates for Resource Limitations when Evaluating National Spread of an Invasive Pathogen

    PubMed Central

    Sutrave, Sweta; Scoglio, Caterina; Isard, Scott A.; Hutchinson, J. M. Shawn; Garrett, Karen A.

    2012-01-01

    Surveying invasive species can be highly resource intensive, yet near-real-time evaluations of invasion progress are important resources for management planning. In the case of the soybean rust invasion of the United States, a linked monitoring, prediction, and communication network saved U.S. soybean growers approximately $200 M/yr. Modeling of future movement of the pathogen (Phakopsora pachyrhizi) was based on data about current disease locations from an extensive network of sentinel plots. We developed a dynamic network model for U.S. soybean rust epidemics, with counties as nodes and link weights a function of host hectarage and wind speed and direction. We used the network model to compare four strategies for selecting an optimal subset of sentinel plots, listed here in order of increasing performance: random selection, zonal selection (based on more heavily weighting regions nearer the south, where the pathogen overwinters), frequency-based selection (based on how frequently the county had been infected in the past), and frequency-based selection weighted by the node strength of the sentinel plot in the network model. When dynamic network properties such as node strength are characterized for invasive species, this information can be used to reduce the resources necessary to survey and predict invasion progress. PMID:22701580

  13. Cortical responses to the mirror box illusion: a high-resolution EEG study.

    PubMed

    Egsgaard, Line Lindhardt; Petrini, Laura; Christoffersen, Giselle; Arendt-Nielsen, Lars

    2011-12-01

    The mirror box illusion has proven a helpful therapy in pathologies such as phantom limb pain, and although the effect has been suggested to be a result of the interaction between pain, vision, touch, and proprioception, the mechanisms are still unknown. Multichannel (124) brain responses were investigated in healthy men (N = 11) and women (N = 14) during the mirror box illusion. Tactile somatosensory evoked potentials were recorded from the right thumb during two control conditions and two illusions: (control 1) no mirror: looking at the physical right thumb during stimulation, (control 2) no mirror: looking at the physical left thumb during stimulation, (illusion 1) mirror: the illusion that both thumbs were stimulated, and (illusion 2) mirror: the illusion that none of the thumbs were stimulated. In men, a significant medial shift in the y coordinate of the N70 dipole in illusion 2 (P = 0.021) was found when compared with illusion 1. No dipole shift was found for women. Additionally, men showed higher prevalence of P180 cingulate cortex activation during illusion 2 when compared with control 1 and 2 (P = 0.002). During illusion 2, the degree of conformity with the statement "The hand in the mirror feels like my other hand" was negatively correlated with the N70 x coordinate for men and positively correlated with the N70 z coordinate for women. In conclusion, short-term cortical plasticity can be induced by a mismatch between visual input and location of tactile stimulation in men. The present study suggests that gender differences exist in the perception of the mirror box illusion.

  14. Stochastic multiscale modelling of cortical bone elasticity based on high-resolution imaging.

    PubMed

    Sansalone, Vittorio; Gagliardi, Davide; Desceliers, Christophe; Bousson, Valérie; Laredo, Jean-Denis; Peyrin, Françoise; Haïat, Guillaume; Naili, Salah

    2016-02-01

    Accurate and reliable assessment of bone quality requires predictive methods which could probe bone microstructure and provide information on bone mechanical properties. Multiscale modelling and simulation represent a fast and powerful way to predict bone mechanical properties based on experimental information on bone microstructure as obtained through X-ray-based methods. However, technical limitations of experimental devices used to inspect bone microstructure may produce blurry data, especially in in vivo conditions. Uncertainties affecting the experimental data (input) may question the reliability of the results predicted by the model (output). Since input data are uncertain, deterministic approaches are limited and new modelling paradigms are required. In this paper, a novel stochastic multiscale model is developed to estimate the elastic properties of bone while taking into account uncertainties on bone composition. Effective elastic properties of cortical bone tissue were computed using a multiscale model based on continuum micromechanics. Volume fractions of bone components (collagen, mineral, and water) were considered as random variables whose probabilistic description was built using the maximum entropy principle. The relevance of this approach was proved by analysing a human bone sample taken from the inferior femoral neck. The sample was imaged using synchrotron radiation micro-computed tomography. 3-D distributions of Haversian porosity and tissue mineral density extracted from these images supplied the experimental information needed to build the stochastic models of the volume fractions. Thus, the stochastic multiscale model provided reliable statistical information (such as mean values and confidence intervals) on bone elastic properties at the tissue scale. Moreover, the existence of a simpler "nominal model", accounting for the main features of the stochastic model, was investigated. It was shown that such a model does exist, and its relevance

  15. High effective cytosolic H+ buffering in mouse cortical astrocytes attributable to fast bicarbonate transport.

    PubMed

    Theparambil, Shefeeq M; Deitmer, Joachim W

    2015-09-01

    Cytosolic H(+) buffering plays a major role for shaping intracellular H(+) shifts and hence for the availability of H(+) for biochemical reactions and acid/base-coupled transport processes. H(+) buffering is one of the prime means to protect the cell from large acid/base shifts. We have used the H(+) indicator dye BCECF and confocal microscopy to monitor the cytosolic H(+) concentration, [H(+)]i, in cultured cortical astrocytes of wild-type mice and of mice deficient in sodium/bicarbonate cotransporter NBCe1 (NBCe1-KO) or in carbonic anhydrase isoform II (CAII-KO). The steady-state buffer strength was calculated from the amplitude of [H(+)]i transients as evoked by CO2/HCO3(-) and by butyric acid in the presence and absence of CO2/HCO3(-). We tested the hypotheses if, in addition to instantaneous physicochemical H(+) buffering, rapid acid/base transport across the cell membrane contributes to the total, "effective" cytosolic H(+) buffering. In the presence of 5% CO2/26 mM HCO3(-), H(+) buffer strength in astrocytes was increased 4-6 fold, as compared with that in non-bicarbonate, HEPES-buffered solution, which was largely attributable to fast HCO3 (-) transport into the cells via NBCe1, supported by CAII activity. Our results show that within the time frame of determining physiological H(+) buffering in cells, fast transport and equilibration of CO2/H(+)/HCO3(-) can make a major contribution to the total "effective" H(+) buffer strength. Thus, "effective" cellular H(+) buffering is, to a large extent, attributable to membrane transport of base equivalents rather than a purely passive physicochemical process, and can be much larger than reported so far. Not only physicochemical H(+) buffering, but also rapid import of HCO3(-) via the electrogenic sodium-bicarbonate cotransporter NBCe1, supported by carbonic anhydrase II (CA II), was identified to enhance cytosolic H(+) buffer strength substantially.

  16. Axial high topography and partial melt in the crust and mantle beneath the western Galápagos Spreading Center

    USGS Publications Warehouse

    Blacic, Tanya M.; Ito, Garrett; Shah, Anjana K.; Canales, Juan Pablo; Lin, Jian

    2008-01-01

    The hot spot-influenced western Galápagos Spreading Center (GSC) has an axial topographic high that reaches heights of ∼700 m relative to seafloor depth ∼25 km from the axis. We investigate the cause of the unusual size of the axial high using a model that determines the flexural response to loads resulting from the thermal and magmatic structure of the lithosphere. The thermal structure simulated is appropriate for large amounts of cooling by hydrothermal circulation, which tends to minimize the amount of partial melt needed to explain the axial topography. Nonetheless, results reveal that the large axial high near 92°W requires that either the crust below the magma lens contains >35% partial melt or that 20% melt is present in the lower crust and at least 3% in the mantle within a narrow column (<∼10 km wide) extending to depths of 45–65 km. Because melt fractions >35% in the crust are considered unreasonable, it is likely that much of the axial high region of the GSC is underlain by a narrow region of partially molten mantle of widths approaching those imaged seismically beneath the East Pacific Rise. A narrow zone of mantle upwelling and melting, driven largely by melt buoyancy, is a plausible explanation.

  17. Evolution, global spread, and pathogenicity of highly pathogenic avian influenza H5Nx clade 2.3.4.4.

    PubMed

    Lee, Dong-Hun; Bertran, Kateri; Kwon, Jung-Hoon; Swayne, David E

    2017-08-31

    Novel subtypes of Asian-origin (Goose/Guangdong lineage) H5 highly pathogenic avian influenza (HPAI) viruses belonging to clade 2.3.4, such as H5N2, H5N5, H5N6, and H5N8, have been identified in China since 2008 and have since evolved into four genetically distinct clade 2.3.4.4 groups (A-D). Since 2014, HPAI clade 2.3.4.4 viruses have spread rapidly via migratory wild aquatic birds and have evolved through reassortment with prevailing local low pathogenicity avian influenza viruses. Group A H5N8 viruses and its reassortant viruses caused outbreaks in wide geographic regions (Asia, Europe, and North America) during 2014-2015. Novel reassortant Group B H5N8 viruses caused outbreaks in Asia, Europe, and Africa during 2016-2017. Novel reassortant Group C H5N6 viruses caused outbreaks in Korea and Japan during the 2016-2017 winter season. Group D H5N6 viruses caused outbreaks in China and Vietnam. A wide range of avian species, including wild and domestic waterfowl, domestic poultry, and even zoo birds, seem to be permissive for infection by and/or transmission of clade 2.3.4.4 HPAI viruses. Further, compared to previous H5N1 HPAI viruses, these reassortant viruses show altered pathogenicity in birds. In this review, we discuss the evolution, global spread, and pathogenicity of H5 clade 2.3.4.4 HPAI viruses.

  18. [Characteristics of cortical activity in persons with high and low verbal creativity: analysis of alpha1,2 rhythms].

    PubMed

    Razumnikova, O M; Tarasova, I V; Vol'f, N V

    2009-01-01

    Creativity-related changes in alpha power in low-frequency (8-10 Hz) and high-frequency (10-13 Hz) bands were studied in university students having regard to generation of original ideas during performance of two verbal tasks. A high-creative group enrolled 16 subjects asked to generate original words--associates to the triads of verbal stimuli and 14 subjects who were asked to compose a sentence using triads of nouns from remote semantic categories. Low-creative groups included 22 and 13 individuals, respectively. In low-frequency band, highly creative subjects showed a higher level of alpha power than low creative individuals. In the high-frequency band, task-related alpha2 power desynchronization was different in these groups: high-creative individuals had higher power score than low-creative mostly in the anterior and parietal cortical areas. These data and a factor structure of alpha rhythm indices may be evidence of different strategies of information selection in highly and low creative persons.

  19. High-resolution and site-specific scanning spreading resistance microscopy and its applications to silicon devices

    SciTech Connect

    Zhang, L.; Koike, M.; Takeno, S.; Hara, K.

    2012-11-06

    Due to the continuous reduction of the critical dimensions of semiconductor devices, it becomes very important to know the two dimensional (2D) doping profile for improving device performance. Scanning spreading resistance microscopy (SSRM) performed in high vacuum is a powerful technique for quantitative 2D-doping profiling, with high spatial resolution and wide dynamic range of carrier concentration, as well as capability of site-specific analysis for accurate position. In this paper, we review SSRM applications to source/drain engineering in Si devices and their correlation with device characteristics by demonstrating several case studies. Direct observation of (110)/(100) CMOSFETs clarified significant differences between both pFETs and nFETs on (110) and (100) silicon substrates, revealing 2D channeling effect of boron ion implantation in pFETs; as well as silicidation impact on junction leakage-current characteristics in nFETs. Furthermore, our sample-preparation breakthrough enables site-specific SSRM characterization within 60 nm ultra thin samples and therefore failure analysis of real SRAM devices, demonstrating the high potential of SSRM technology for further device scaling and for failure analysis.

  20. Human cortical rhythms during visual delayed choice reaction time tasks. A high-resolution EEG study on normal aging.

    PubMed

    Babiloni, Claudio; Babiloni, Fabio; Carducci, Filippo; Cappa, Stefano F; Cincotti, Febo; Del Percio, Claudio; Miniussi, Carlo; Vito Moretti, Davide; Rossi, Simone; Sosta, Katiuscia; Rossini, Paolo Maria

    2004-08-12

    Neuroimaging cognitive study of aging requires simple tasks ensuring a high rate of correct performances even in stressful neurophysiological settings. Here two simple delayed choice reaction time tasks were used to unveil event-related desynchronization (ERD) of theta (4-6 Hz) and alpha (6-12 Hz) electroencephalographic rhythms across normal aging. In the first condition, a cue stimulus (one bit) was memorized along a brief delay period (3.5-5.5 s). The explicit demand was visuo-spatial, but the retention could be also based on phonological and somatomotor coding. In the second condition, the cue stimulus remained available along the delay period. Correct performances were higher than 95% in both groups and tasks, although they were significantly better in young than elderly subjects (P < 0.03). During the delay period, theta and alpha ERD accompanying correct responses were recognized in the two groups, the alpha ERD being stronger and prolonged during the memory than non-memory task. On the other hand, the fronto-parietal theta and parietal alpha ERD were stronger in young than elderly subjects during both tasks. Notably, the frontal alpha ERD was negligible in elderly subjects. In conclusion, the present simple tasks unveiled in elderly compared to young subjects (i) a weaker involvement of (para)hippocampal-cortical circuits as revealed by theta ERD and (ii) a weaker involvement of "executive" thalamo-cortical circuits as revealed by frontal alpha ERD. These effects might worsen behavioral performances to the simple cognitive tasks with age. The present protocol is promising for the neuroimaging study of pathological aging.

  1. Comparing cortical plasticity induced by conventional and high-definition 4 × 1 ring tDCS: a neurophysiological study.

    PubMed

    Kuo, Hsiao-I; Bikson, Marom; Datta, Abhishek; Minhas, Preet; Paulus, Walter; Kuo, Min-Fang; Nitsche, Michael A

    2013-07-01

    Transcranial direct current stimulation (tDCS) induces long-lasting NMDA receptor-dependent cortical plasticity via persistent subthreshold polarization of neuronal membranes. Conventional bipolar tDCS is applied with two large (35 cm(2)) rectangular electrodes, resulting in directional modulation of neuronal excitability. Recently a newly designed 4 × 1 high-definition (HD) tDCS protocol was proposed for more focal stimulation according to the results of computational modeling. HD tDCS utilizes small disc electrodes deployed in 4 × 1 ring configuration whereby the physiological effects of the induced electric field are thought to be grossly constrained to the cortical area circumscribed by the ring. We aim to compare the physiological effects of both tDCS electrode arrangements on motor cortex excitability. tDCS was applied with 2 mA for 10 min. Fourteen healthy subjects participated, and motor cortex excitability was monitored by transcranial magnetic stimulation (TMS) before and after tDCS. Excitability enhancement following anodal and a respective reduction after cathodal stimulation occurred in both, conventional and HD tDCS. However, the plastic changes showed a more delayed peak at 30 min and longer lasting after-effects for more than 2 h after HD tDCS for both polarities, as compared to conventional tDCS. The results show that this new electrode arrangement is efficient for the induction of neuroplasticity in the primary motor cortex. The pattern of aftereffects might be compatible with the concept of GABA-mediated surround inhibition, which should be explored in future studies directly. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Pharmacological characterization of metabotropic glutamate receptor-mediated high-affinity GTPase activity in rat cerebral cortical membranes

    PubMed Central

    Nishi, Nobuyuki; Odagaki, Yuji; Koyama, Tsukasa

    2000-01-01

    Activation of heterotrimeric guanine nucleotide-binding regulatory proteins (G-proteins) functionally coupled to metabotropic glutamate receptors (mGluRs) was assessed by agonist-induced high-affinity GTPase (EC3.6.1.-) activity in rat cerebral cortical membranes. L-Glutamate (1 mM) stimulated high-affinity GTPase activity to the same extent throughout the incubation period up to 20 min, in a Mg2+-dependent manner. The addition of 1 mM L-glutamate augmented Vmax of the enzyme activity (1670 to 3850 pmol mg−1 protein 15 min−1) with slight increase in KM value (0.26 to 0.63 μM). The high-affinity GTPase activity was stimulated by the following compounds with a rank order of potency of (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl) glycine (DCG-IV) >  (2S,1′S,2′S)-2-(carboxycyclopyropyl)glycine (L-CCG-I) > L-glutamate ≥ 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate [(2R,4R)-APDC] > 1S,3R-1-aminocyclopentane-1,3-dicarboxylate [(1S,3R)-ACPD] > (S)-4-carboxy-3-hydroxyphenylglycine [(S)-4C3HPG] > (S)-3-carboxy-4-hydroxyphenylglycine [(S)-3C4HPG] > ibotenate, but not by L-(+)-2-amino-4-phosphonobutyrate (L-AP4), (RS)-3,5-dihydroxyphenylglycine [(RS)-3,5-DHPG], quisqualate, or L-serine-O-phosphate (L-SOP), indicative of involvement of group II mGluRs, in particular mGluR2. (2S)-α-Ethylglutamate (EGLU), a presumably selective antagonist against group II mGluRs, inhibited DCG-IV-stimulated high-affinity GTPase activity in a competitive manner with an apparent KB of 220 μM. L-Glutamate-stimulated activity was eliminated by pretreatment of the membranes with sulfhydryl alkylating agent N-ethylmaleimide (NEM) at 30–50 μM, indicating that G-proteins of the Gi family are involved. These results indicate that mGluR agonist-induced high-affinity GTPase activity in rat cerebral cortical membranes may be used to detect the functional interaction between group II mGluRs, in particular mGluR2, and NEM-sensitive Gi proteins. PMID:10928972

  3. A High-throughput Assay for mRNA Silencing in Primary Cortical Neurons in vitro with Oligonucleotide Therapeutics.

    PubMed

    Alterman, Julia F; Coles, Andrew H; Hall, Lauren M; Aronin, Neil; Khvorova, Anastasia; Didiot, Marie-Cécile

    2017-08-20

    Primary neurons represent an ideal cellular system for the identification of therapeutic oligonucleotides for the treatment of neurodegenerative diseases. However, due to the sensitive nature of primary cells, the transfection of small interfering RNAs (siRNA) using classical methods is laborious and often shows low efficiency. Recent progress in oligonucleotide chemistry has enabled the development of stabilized and hydrophobically modified small interfering RNAs (hsiRNAs). This new class of oligonucleotide therapeutics shows extremely efficient self-delivery properties and supports potent and durable effects in vitro and in vivo. We have developed a high-throughput in vitro assay to identify and test hsiRNAs in primary neuronal cultures. To simply, rapidly, and accurately quantify the mRNA silencing of hundreds of hsiRNAs, we use the QuantiGene 2.0 quantitative gene expression assay. This high-throughput, 96-well plate-based assay can quantify mRNA levels directly from sample lysate. Here, we describe a method to prepare short-term cultures of mouse primary cortical neurons in a 96-well plate format for high-throughput testing of oligonucleotide therapeutics. This method supports the testing of hsiRNA libraries and the identification of potential therapeutics within just two weeks. We detail methodologies of our high throughput assay workflow from primary neuron preparation to data analysis. This method can help identify oligonucleotide therapeutics for treatment of various neurological diseases.

  4. Cortical commands in active touch.

    PubMed

    Brecht, Michael

    2006-01-01

    The neocortex is an enormous network of extensively interconnected neurons. It has become clear that the computations performed by individual cortical neurons will critically depend on the quantitative composition of cortical activity. Here we discuss quantitative aspects of cortical activity and modes of cortical processing in the context of rodent active touch. Through in vivo whole-cell recordings one observes widespread subthreshold and very sparse evoked action potential (AP) activity in the somatosensory cortex both for passive whisker deflection in anaesthetized animals and during active whisker movements in awake animals. Neurons of the somatosensory cortex become either suppressed during whisking or activated by an efference copy of whisker movement signal that depolarize cells at certain phases of the whisking cycle. To probe the read out of cortical motor commands we applied intracellular stimulation in rat whisker motor cortex. We find that APs in individual cortical neurons can evoke long sequences of small whisker movements. The capacity of an individual neuron to evoke movements is most astonishing given the large number of neurons in whisker motor cortex. Thus, few cortical APs may suffice to control motor behaviour and such APs can be translated into action with the utmost precision. We conclude that there is very widespread subthreshold cortical activity and very sparse, highly specific cortical AP activity.

  5. Spread Supersymmetry

    NASA Astrophysics Data System (ADS)

    Hall, Lawrence J.; Nomura, Yasunori

    2012-01-01

    In the multiverse the scale of supersymmetry breaking, widetilde{m} = {F_X}/{M_{ * }} ∗, may scan and environmental constraints on the dark matter density may exclude a large range of m from the reheating temperature after inflation down to values that yield a lightest supersymmetric particle (LSP) mass of order a TeV. After selection effects, for example from the cosmological constant, the distribution for widetilde{m} in the region that gives a TeV LSP may prefer larger values. A single environmental constraint from dark matter can then lead to multi-component dark matter, including both axions and the LSP, giving a TeV-scale LSP somewhat lighter than the corresponding value for single-component LSP dark matter. If supersymmetry breaking is mediated to the Standard Model sector at order X † X and higher, only squarks, sleptons and one Higgs doublet acquire masses of order widetilde{m} . The gravitino mass is lighter by a factor of M ∗ /M Pl and the gaugino masses are suppressed by a further loop factor. This Spread Supersymmetry spectrum has two versions, one with Higgsino masses arising from supergravity effects of order the gravitino mass giving a wino LSP, and another with the Higgsino masses generated radiatively from gaugino masses giving a Higgsino LSP. The environmental restriction on dark matter fixes the LSP mass to the TeV domain, so that the squark and slepton masses are order 103 TeV and 106 TeV in these two schemes. We study the spectrum, dark matter and collider signals of these two versions of Spread Supersymmetry. The Higgs boson is Standard Model-like and predicted to lie in the range 110-145 GeV; monochromatic photons in cosmic rays arise from dark matter annihilations in the halo; exotic short charged tracks occur at the LHC, at least for the wino LSP; and there are the eventual possibilities of direct detection of dark matter and detailed exploration of the TeV-scale states at a future linear collider. Gauge coupling unification is at

  6. Correlates of spreading depolarization in human scalp electroencephalography.

    PubMed

    Drenckhahn, Christoph; Winkler, Maren K L; Major, Sebastian; Scheel, Michael; Kang, Eun-Jeung; Pinczolits, Alexandra; Grozea, Cristian; Hartings, Jed A; Woitzik, Johannes; Dreier, Jens P

    2012-03-01

    It has been known for decades that suppression of spontaneous scalp electroencephalographic activity occurs during ischaemia. Trend analysis for such suppression was found useful for intraoperative monitoring during carotid endarterectomy, or as a screening tool to detect delayed cerebral ischaemia after aneurismal subarachnoid haemorrhage. Nevertheless, pathogenesis of such suppression of activity has remained unclear. In five patients with aneurismal subarachnoid haemorrhage and four patients with decompressive hemicraniectomy after malignant hemispheric stroke due to middle cerebral artery occlusion, we here performed simultaneously full-band direct and alternating current electroencephalography at the scalp and direct and alternating current electrocorticography at the cortical surface. After subarachnoid haemorrhage, 275 slow potential changes, identifying spreading depolarizations, were recorded electrocorticographically over 694 h. Visual inspection of time-compressed scalp electroencephalography identified 193 (70.2%) slow potential changes [amplitude: -272 (-174, -375) µV (median quartiles), duration: 5.4 (4.0, 7.1) min, electrocorticography-electroencephalography delay: 1.8 (0.8, 3.5) min]. Intervals between successive spreading depolarizations were significantly shorter for depolarizations with electroencephalographically identified slow potential change [33.0 (27.0, 76.5) versus 53.0 (28.0, 130.5) min, P = 0.009]. Electroencephalography was thus more likely to display slow potential changes of clustered than isolated spreading depolarizations. In contrast to electrocorticography, no spread of electroencephalographic slow potential changes was seen, presumably due to superposition of volume-conducted electroencephalographic signals from widespread cortical generators. In two of five patients with subarachnoid haemorrhage, serial magnetic resonance imaging revealed large delayed infarcts at the recording site, while electrocorticography showed clusters

  7. Low and High-Frequency Field Potentials of Cortical Networks Exhibit Distinct Responses to Chemicals

    EPA Science Inventory

    Neural networks grown on microelectrode arrays (MEAs) have become an important, high content in vitro assay for assessing neuronal function. MEA experiments typically examine high- frequency (HF) (>200 Hz) spikes, and bursts which can be used to discriminate between differ...

  8. The Role of Epidemic Resistance Plasmids and International High-Risk Clones in the Spread of Multidrug-Resistant Enterobacteriaceae

    PubMed Central

    Mathers, Amy J.; Peirano, Gisele

    2015-01-01

    SUMMARY Escherichia coli sequence type 131 (ST131) and Klebsiella pneumoniae ST258 emerged in the 2000s as important human pathogens, have spread extensively throughout the world, and are responsible for the rapid increase in antimicrobial resistance among E. coli and K. pneumoniae strains, respectively. E. coli ST131 causes extraintestinal infections and is often fluoroquinolone resistant and associated with extended-spectrum β-lactamase production, especially CTX-M-15. K. pneumoniae ST258 causes urinary and respiratory tract infections and is associated with carbapenemases, most often KPC-2 and KPC-3. The most prevalent lineage within ST131 is named fimH30 because it contains the H30 variant of the type 1 fimbrial adhesin gene, and recent molecular studies have demonstrated that this lineage emerged in the early 2000s and was then followed by the rapid expansion of its sublineages H30-R and H30-Rx. K. pneumoniae ST258 comprises 2 distinct lineages, namely clade I and clade II. Moreover, it seems that ST258 is a hybrid clone that was created by a large recombination event between ST11 and ST442. Epidemic plasmids with blaCTX-M and blaKPC belonging to incompatibility group F have contributed significantly to the success of these clones. E. coli ST131 and K. pneumoniae ST258 are the quintessential examples of international multidrug-resistant high-risk clones. PMID:25926236

  9. Improving Transferability of Introduced Species’ Distribution Models: New Tools to Forecast the Spread of a Highly Invasive Seaweed

    PubMed Central

    Verbruggen, Heroen; Tyberghein, Lennert; Belton, Gareth S.; Mineur, Frederic; Jueterbock, Alexander; Hoarau, Galice; Gurgel, C. Frederico D.; De Clerck, Olivier

    2013-01-01

    The utility of species distribution models for applications in invasion and global change biology is critically dependent on their transferability between regions or points in time, respectively. We introduce two methods that aim to improve the transferability of presence-only models: density-based occurrence thinning and performance-based predictor selection. We evaluate the effect of these methods along with the impact of the choice of model complexity and geographic background on the transferability of a species distribution model between geographic regions. Our multifactorial experiment focuses on the notorious invasive seaweed Caulerpacylindracea (previously Caulerparacemosa var. cylindracea) and uses Maxent, a commonly used presence-only modeling technique. We show that model transferability is markedly improved by appropriate predictor selection, with occurrence thinning, model complexity and background choice having relatively minor effects. The data shows that, if available, occurrence records from the native and invaded regions should be combined as this leads to models with high predictive power while reducing the sensitivity to choices made in the modeling process. The inferred distribution model of Caulerpacylindracea shows the potential for this species to further spread along the coasts of Western Europe, western Africa and the south coast of Australia. PMID:23950789

  10. Detection of high-energy phosphates in cortical bone as an indicator of bone healing and remodelling: use of a rabbit model.

    PubMed

    Buchholz, J; Huber, F X; Meeder, P J; Muhr, G; Kreitz, G K; Herzog, L

    2004-12-01

    PURPOSE; To study high-energy phosphates in cortical bone through experiments on inbred white New Zealand rabbits. Tibial fractures were induced in 80 rabbits and then stabilised by screw osteosynthesis. After 3 (group A; n=40) or 7 days (groups B; n=40), the defective tissue was covered by local muscle flaps. At increasing intervals (from 1 to 16 weeks), the screws were removed and the animals were euthanised (n=8 per group). The bone was removed and analysed histomorphologically; adenosine triphosphate (ATP) levels were determined by high-performance liquid chromatography. The mean ATP concentration in healthy cortical bone at 16 weeks was 0.092 (standard error, 0.009) nmol/mg dry mass, which was significantly higher than that in the group with delayed healing: 0.081 (0.011) nmol/mg in group A and 0.005 (0.001) nmol/mg in group B (paired t test, p<0.05). Earlier healing led to lower rates of necrosis (0 vs 38; groups A vs B) and osteomyelitis. Early muscle-flap coverage can revascularise the cortical bone, which is reflected in the higher ATP content in the cortical bone measured by high-performance liquid chromatography. Measuring changes of ATP levels can help investigate the metabolism of the pathological bone.

  11. SPREAD: a high-resolution daily gridded precipitation dataset for Spain - an extreme events frequency and intensity overview

    NASA Astrophysics Data System (ADS)

    Serrano-Notivoli, Roberto; Beguería, Santiago; Ángel Saz, Miguel; Longares, Luis Alberto; de Luis, Martín

    2017-09-01

    A high-resolution daily gridded precipitation dataset was built from raw data of 12 858 observatories covering a period from 1950 to 2012 in peninsular Spain and 1971 to 2012 in Balearic and Canary islands. The original data were quality-controlled and gaps were filled on each day and location independently. Using the serially complete dataset, a grid with a 5 × 5 km spatial resolution was constructed by estimating daily precipitation amounts and their corresponding uncertainty at each grid node. Daily precipitation estimations were compared to original observations to assess the quality of the gridded dataset. Four daily precipitation indices were computed to characterise the spatial distribution of daily precipitation and nine extreme precipitation indices were used to describe the frequency and intensity of extreme precipitation events. The Mediterranean coast and the Central Range showed the highest frequency and intensity of extreme events, while the number of wet days and dry and wet spells followed a north-west to south-east gradient in peninsular Spain, from high to low values in the number of wet days and wet spells and reverse in dry spells. The use of the total available data in Spain, the independent estimation of precipitation for each day and the high spatial resolution of the grid allowed for a precise spatial and temporal assessment of daily precipitation that is difficult to achieve when using other methods, pre-selected long-term stations or global gridded datasets. SPREAD dataset is publicly available at https://doi.org/10.20350/digitalCSIC/7393.

  12. High energy x-ray diffraction/x-ray fluorescence spectroscopy for high-throughput analysis of composition spread thin films

    SciTech Connect

    Gregoire, John M.; Dale, Darren; Kazimirov, Alexander; DiSalvo, Francis J.; Dover, R. Bruce van

    2009-12-15

    High-throughput crystallography is an important tool in materials research, particularly for the rapid assessment of structure-property relationships. We present a technique for simultaneous acquisition of diffraction images and fluorescence spectra on a continuous composition spread thin film using a 60 keV x-ray source. Subsequent noninteractive data processing provides maps of the diffraction profiles, thin film fiber texture, and composition. Even for highly textured films, our diffraction technique provides detection of diffraction from each family of Bragg reflections, which affords direct comparison of the measured profiles with powder patterns of known phases. These techniques are important for high throughput combinatorial studies as they provide structure and composition maps which may be correlated with performance trends within an inorganic library.

  13. Cortical Control of Zona Incerta

    PubMed Central

    Barthó, Péter; Slézia, Andrea; Varga, Viktor; Bokor, Hajnalka; Pinault, Didier; Buzsáki, György; Acsády, László

    2009-01-01

    The zona incerta (ZI) is at the crossroad of almost all major ascending and descending fiber tracts and targets numerous brain centers from the thalamus to the spinal cord. Effective ascending drive of ZI cells has been described, but the role of descending cortical signals in patterning ZI activity is unknown. Cortical control over ZI function was examined during slow cortical waves (1-3 Hz), paroxysmal high-voltage spindles (HVSs), and 5-9 Hz oscillations in anesthetized rats. In all conditions, rhythmic cortical activity significantly altered the firing pattern of ZI neurons recorded extracellularly and labeled with the juxtacellular method. During slow oscillations, the majority of ZI neurons became synchronized to the depth-negative phase (“up state”) of the cortical waves to a degree comparable to thalamocortical neurons. During HVSs, ZI cells displayed highly rhythmic activity in tight synchrony with the cortical oscillations. ZI neurons responded to short epochs of cortical 5-9 Hz oscillations, with a change in the interspike interval distribution and with an increase in spectral density in the 5-9 Hz band as measured by wavelet analysis. Morphological reconstruction revealed that most ZI cells have mediolaterally extensive dendritic trees and very long dendritic segments. Cortical terminals established asymmetrical synapses on ZI cells with very long active zones. These data suggest efficient integration of widespread cortical signals by single ZI neurons and strong cortical drive. We propose that the efferent GABAergic signal of ZI neurons patterned by the cortical activity can play a critical role in synchronizing thalamocortical and brainstem rhythms. PMID:17301175

  14. Resveratrol supplementation confers neuroprotection in cortical brain tissue of nonhuman primates fed a high-fat/sucrose diet

    PubMed Central

    Bernier, Michel; Wahl, Devin; Ali, Ahmed; Allard, Joanne; Faulkner, Shakeela; Wnorowski, Artur; Sanghvi, Mitesh; Moaddel, Ruin; Alfaras, Irene; Mattison, Julie A.; Tarantini, Stefano; Tucsek, Zsuzsanna; Ungvari, Zoltan; Csiszar, Anna; Pearson, Kevin J.; de Cabo, Rafael

    2016-01-01

    Previous studies have shown positive effects of long-term resveratrol (RSV) supplementation in preventing pancreatic beta cell dysfunction, arterial stiffening and metabolic decline induced by high-fat/high-sugar (HFS) diet in nonhuman primates. Here, the analysis was extended to examine whether RSV may reduce dietary stress toxicity in the cerebral cortex of the same cohort of treated animals. Middle-aged male rhesus monkeys were fed for 2 years with HFS alone or combined with RSV, after which whole-genome microarray analysis of cerebral cortex tissue was carried out along with ELISA, immunofluorescence, and biochemical analyses to examine markers of vascular health and inflammation in the cerebral cortices. A number of genes and pathways that were differentially modulated in these dietary interventions indicated an exacerbation of neuroinflammation (e.g., oxidative stress markers, apoptosis, NF-κB activation) in HFS-fed animals and protection by RSV treatment. The decreased expression of mitochondrial aldehyde dehydrogenase 2, dysregulation in endothelial nitric oxide synthase, and reduced capillary density induced by HFS stress were rescued by RSV supplementation. Our results suggest that long-term RSV treatment confers neuroprotection against cerebral vascular dysfunction during nutrient stress. PMID:27070252

  15. Mechanical strain, induced noninvasively in the high-frequency domain, is anabolic to cancellous bone, but not cortical bone.

    PubMed

    Rubin, C; Turner, A S; Mallinckrodt, C; Jerome, C; McLeod, K; Bain, S

    2002-03-01

    Departing from the premise that it is the large-amplitude signals inherent to intense functional activity that define bone morphology, we propose that it is the far lower magnitude, high-frequency mechanical signals that continually barrage the skeleton during longer term activities such as standing, which regulate skeletal architecture. To examine this hypothesis, we proposed that brief exposure to slight elevations in these endogenous mechanical signals would suffice to increase bone mass in those bones subject to the stimulus. This was tested by exposing the hind limbs of adult female sheep (n = 9) to 20 min/day of low-level (0.3g), high-frequency (30 Hz) mechanical signals, sufficient to induce a peak of approximately 5 microstrain (micro epsilon) in the tibia. Following euthanasia, peripheral quantitative computed tomography (pQCT) was used to segregate the cortical shell from the trabecular envelope of the proximal femur, revealing a 34.2% increase in bone density in the experimental animals as compared with controls (p = 0.01). Histomorphometric examination of the femur supported these density measurements, with bone volume per total volume increasing by 32% (p = 0.04). This density increase was achieved by two separate strategies: trabecular spacing decreased by 36.1% (p = 0.02), whereas trabecular number increased by 45.6% (p = 0.01), indicating the formation of cancellous bone de novo. There were no significant differences in the radii of animals subject to the stimulus, indicating that the adaptive response was local rather than systemic. The anabolic potential of the signal was evident only in trabecular bone, and there were no differences, as measured by any assay, in the cortical bone. These data suggest that subtle mechanical signals generated during predominant activities such as posture may be potent determinants of skeletal morphology. Given that these strain levels are three orders of magnitude below strains that can damage bone tissue, we

  16. High gamma power in ECoG reflects cortical electrical stimulation effects on unit activity in layers V/VI

    NASA Astrophysics Data System (ADS)

    Yazdan-Shahmorad, Azadeh; Kipke, Daryl R.; Lehmkuhle, Mark J.

    2013-12-01

    Objective. Cortical electrical stimulation (CES) has been used extensively in experimental neuroscience to modulate neuronal or behavioral activity, which has led this technique to be considered in neurorehabilitation. Because the cortex and the surrounding anatomy have irregular geometries as well as inhomogeneous and anisotropic electrical properties, the mechanism by which CES has therapeutic effects is poorly understood. Therapeutic effects of CES can be improved by optimizing the stimulation parameters based on the effects of various stimulation parameters on target brain regions. Approach. In this study we have compared the effects of CES pulse polarity, frequency, and amplitude on unit activity recorded from rat primary motor cortex with the effects on the corresponding local field potentials (LFP), and electrocorticograms (ECoG). CES was applied at the surface of the cortex and the unit activity and LFPs were recorded using a penetrating electrode array, which was implanted below the stimulation site. ECoGs were recorded from the vicinity of the stimulation site. Main results. Time-frequency analysis of LFPs following CES showed correlation of gamma frequencies with unit activity response in all layers. More importantly, high gamma power of ECoG signals only correlated with the unit activity in lower layers (V-VI) following CES. Time-frequency correlations, which were found between LFPs, ECoGs and unit activity, were frequency- and amplitude-dependent. Significance. The signature of the neural activity observed in LFP and ECoG signals provides a better understanding of the effects of stimulation on network activity, representative of large numbers of neurons responding to stimulation. These results demonstrate that the neurorehabilitation and neuroprosthetic applications of CES targeting layered cortex can be further improved by using field potential recordings as surrogates to unit activity aimed at optimizing stimulation efficacy. Likewise, the signatures

  17. Surfactant Driven Post-Deposition Spreading of Aerosols on Complex Aqueous Subphases. 1: High Deposition Flux Representative of Aerosol Delivery to Large Airways.

    PubMed

    Khanal, Amsul; Sharma, Ramankur; Corcoran, Timothy E; Garoff, Stephen; Przybycien, Todd M; Tilton, Robert D

    2015-10-01

    Aerosol drug delivery is a viable option for treating diseased airways, but airway obstructions associated with diseases such as cystic fibrosis cause non-uniform drug distribution and limit efficacy. Marangoni stresses produced by surfactant addition to aerosol formulations may enhance delivery uniformity by post-deposition spreading of medications over the airway surface, improving access to poorly ventilated regions. We examine the roles of different variables affecting the maximum post-deposition spreading of a dye (drug mimic). Entangled aqueous solutions of either poly(acrylamide) (PA) or porcine gastric mucin (PGM) serve as airway surface liquid (ASL) mimicking subphases for in vitro models of aerosol deposition. Measured aerosol deposition fluxes indicate that the experimental delivery conditions are representative of aerosol delivery to the conducting airways. Post-deposition spreading beyond the locale of direct aerosol deposition is tracked by fluorescence microscopy. Aqueous aerosols formulated with either nonionic surfactant (tyloxapol) or fluorosurfactant (FS-3100) are compared with surfactant-free control aerosols. Significant enhancement of post-deposition spreading is observed with surfactant solutions relative to surfactant-free control solutions, provided the surfactant solution surface tension is less than that of the subphase. Amongst the variables considered--surfactant concentration, aerosol flow-rate, total deposited volume, time of delivery, and total deposited surfactant mass--surfactant mass is the primary predictor of maximum spread distance. This dependence is also observed for solutions deposited as a single, microliter-scale drop with a volume comparable to the total volume of deposited aerosol. Marangoni stress-assisted spreading after surfactant-laden aerosol deposition at high fluxes on a complex fluid subphase is capable of driving aerosol contents over significantly greater distances compared to surfactant-free controls. Total

  18. Surfactant Driven Post-Deposition Spreading of Aerosols on Complex Aqueous Subphases. 1: High Deposition Flux Representative of Aerosol Delivery to Large Airways

    PubMed Central

    Khanal, Amsul; Sharma, Ramankur; Corcoran, Timothy E.; Przybycien, Todd M.; Tilton, Robert D.

    2015-01-01

    Abstract Background: Aerosol drug delivery is a viable option for treating diseased airways, but airway obstructions associated with diseases such as cystic fibrosis cause non-uniform drug distribution and limit efficacy. Marangoni stresses produced by surfactant addition to aerosol formulations may enhance delivery uniformity by post-deposition spreading of medications over the airway surface, improving access to poorly ventilated regions. We examine the roles of different variables affecting the maximum post-deposition spreading of a dye (drug mimic). Methods: Entangled aqueous solutions of either poly(acrylamide) (PA) or porcine gastric mucin (PGM) serve as airway surface liquid (ASL) mimicking subphases for in vitro models of aerosol deposition. Measured aerosol deposition fluxes indicate that the experimental delivery conditions are representative of aerosol delivery to the conducting airways. Post-deposition spreading beyond the locale of direct aerosol deposition is tracked by fluorescence microscopy. Aqueous aerosols formulated with either nonionic surfactant (tyloxapol) or fluorosurfactant (FS-3100) are compared with surfactant-free control aerosols. Results: Significant enhancement of post-deposition spreading is observed with surfactant solutions relative to surfactant-free control solutions, provided the surfactant solution surface tension is less than that of the subphase. Amongst the variables considered—surfactant concentration, aerosol flow-rate, total deposited volume, time of delivery, and total deposited surfactant mass—surfactant mass is the primary predictor of maximum spread distance. This dependence is also observed for solutions deposited as a single, microliter-scale drop with a volume comparable to the total volume of deposited aerosol. Conclusions: Marangoni stress-assisted spreading after surfactant-laden aerosol deposition at high fluxes on a complex fluid subphase is capable of driving aerosol contents over significantly greater

  19. Ischemia-induced spreading depolarization in the retina

    PubMed Central

    Srienc, Anja I; Biesecker, Kyle R; Shimoda, Angela M; Kur, Joanna

    2016-01-01

    Cortical spreading depolarization is a metabolically costly phenomenon that affects the brain in both health and disease. Following severe stroke, subarachnoid hemorrhage, or traumatic brain injury, cortical spreading depolarization exacerbates tissue damage and enlarges infarct volumes. It is not known, however, whether spreading depolarization also occurs in the retina in vivo. We report now that spreading depolarization episodes are generated in the in vivo rat retina following retinal vessel occlusion produced by photothrombosis. The properties of retinal spreading depolarization are similar to those of cortical spreading depolarization. Retinal spreading depolarization waves propagate at a velocity of 3.0 ± 0.1 mm/min and are associated with a negative shift in direct current potential, a transient cessation of neuronal spiking, arteriole constriction, and a decrease in tissue O2 tension. The frequency of retinal spreading depolarization generation in vivo is reduced by administration of the NMDA antagonist MK-801 and the 5-HT(1D) agonist sumatriptan. Branch retinal vein occlusion is a leading cause of vision loss from vascular disease. Our results suggest that retinal spreading depolarization could contribute to retinal damage in acute retinal ischemia and demonstrate that pharmacological agents can reduce retinal spreading depolarization frequency after retinal vessel occlusion. Blocking retinal spreading depolarization generation may represent a therapeutic strategy for preserving vision in branch retinal vein occlusion patients. PMID:27389181

  20. Explaining the high voice superiority effect in polyphonic music: evidence from cortical evoked potentials and peripheral auditory models.

    PubMed

    Trainor, Laurel J; Marie, Céline; Bruce, Ian C; Bidelman, Gavin M

    2014-02-01

    Natural auditory environments contain multiple simultaneously-sounding objects and the auditory system must parse the incoming complex sound wave they collectively create into parts that represent each of these individual objects. Music often similarly requires processing of more than one voice or stream at the same time, and behavioral studies demonstrate that human listeners show a systematic perceptual bias in processing the highest voice in multi-voiced music. Here, we review studies utilizing event-related brain potentials (ERPs), which support the notions that (1) separate memory traces are formed for two simultaneous voices (even without conscious awareness) in auditory cortex and (2) adults show more robust encoding (i.e., larger ERP responses) to deviant pitches in the higher than in the lower voice, indicating better encoding of the former. Furthermore, infants also show this high-voice superiority effect, suggesting that the perceptual dominance observed across studies might result from neurophysiological characteristics of the peripheral auditory system. Although musically untrained adults show smaller responses in general than musically trained adults, both groups similarly show a more robust cortical representation of the higher than of the lower voice. Finally, years of experience playing a bass-range instrument reduces but does not reverse the high voice superiority effect, indicating that although it can be modified, it is not highly neuroplastic. Results of new modeling experiments examined the possibility that characteristics of middle-ear filtering and cochlear dynamics (e.g., suppression) reflected in auditory nerve firing patterns might account for the higher-voice superiority effect. Simulations show that both place and temporal AN coding schemes well-predict a high-voice superiority across a wide range of interval spacings and registers. Collectively, we infer an innate, peripheral origin for the higher-voice superiority observed in human

  1. High-calcium diet modulates effects of long-term prolactin exposure on the cortical bone calcium content in ovariectomized rats.

    PubMed

    Charoenphandhu, Narattaphol; Tudpor, Kukiat; Thongchote, Kanogwun; Saengamnart, Wasana; Puntheeranurak, Supaporn; Krishnamra, Nateetip

    2007-02-01

    High physiological prolactin induced positive calcium balance by stimulating intestinal calcium absorption, reducing renal calcium excretion, and increasing bone calcium deposition in female rats. Although prolactin-induced increase in trabecular bone calcium deposition was absent after ovariectomy, its effects on cortical bones were still controversial. The present investigation, therefore, aimed to study the effect of in vivo long-term high physiological prolactin induced by either anterior pituitary (AP) transplantation or 2.5 mg/kg prolactin injection on cortical bones in ovariectomized rats. Since the presence of prolactin receptors (PRLR) in different bones of normal adult rats has not been reported, we first determined mRNA expression of both short- and long-form PRLRs at the cortical sites (tibia and femur) and trabecular sites (calvaria and vertebrae) by using the RT-PCR. Our results showed the mRNA expression of both PRLR isoforms with predominant long form at all sites. However, high prolactin levels induced by AP transplantation in normal rats did not have any effect on the femoral bone mineral density or bone mineral content. By using (45)Ca kinetic study, 2.5 mg/kg prolactin did not alter bone formation, bone resorption, calcium deposition, and total calcium content in tibia and femur of adult ovariectomized rats. AP transplantation also had no effect on the cortical total calcium content in adult ovariectomized rats. Because previous work showed that the effects of prolactin were age dependent and could be modulated by high-calcium diet, interactions between prolactin and these two parameters were investigated. The results demonstrated that 2.0% wt/wt high-calcium diet significantly increased the tibial total calcium content in 9-wk-old young AP-grafted ovariectomized rats but decreased the tibial total calcium content in 22-wk-old adult rats. As for the vertebrae, the total calcium contents in both young and adult rats were not changed by high

  2. Effects of high temperature and exposure to air on mussel (Mytilus galloprovincialis, Lmk 1819) hemocyte phagocytosis: modulation of spreading and oxidative response.

    PubMed

    Mosca, Francesco; Narcisi, Valeria; Calzetta, Angela; Gioia, Luisa; Finoia, Maria G; Latini, Mario; Tiscar, Pietro G

    2013-06-01

    Hemocytes are a critical component of the mussel defense system and the present study aims at investigating their spreading and oxidative properties during phagocytosis under in vivo experimental stress conditions. The spreading ability was measured by an automated cell analyzer on the basis of the circularity, a parameter corresponding to the hemocyte roundness. The oxidative activity was investigated by micromethod assay, measuring the respiratory burst as expression of the fluorescence generated by the oxidation of specific probe. Following the application of high temperature and exposure to air, there was evidence of negative modulation of spreading and oxidative response, as revealed by a cell roundness increase and fluorescence generation decrease. Therefore, the fall of respiratory burst appeared as matched with the inhibition of hemocyte morphological activation, suggesting a potential depression of the phagocytosis process and confirming the application of the circularity parameter as potential stress marker, both in experimental and field studies.

  3. Spreading and slope instability at the continental margin offshore Mt Etna, imaged by high-resolution 2D seismic data

    NASA Astrophysics Data System (ADS)

    Gross, Felix; Krastel, Sebastian; Behrmann, Jan-Hinrich; Papenberg, Cord; Geersen, Jacob; Ridente, Domenico; Latino Chiocci, Francesco; Urlaub, Morelia; Bialas, Jörg; Micallef, Aaron

    2015-04-01

    Mount Etna is the largest active volcano in Europe. Its volcano edifice is located on top of continental crust close to the Ionian shore in east Sicily. Instability of the eastern flank of the volcano edifice is well documented onshore. The continental margin is supposed to deform as well. Little, however, is known about the offshore extension of the eastern volcano flank and its adjacent continental margin, which is a serious shortcoming in stability models. In order to better constrain the active tectonics of the continental margin offshore the eastern flank of the volcano, we acquired and processed a new marine high-resolution seismic and hydro-acoustic dataset. The data provide new detailed insights into the heterogeneous geology and tectonics of shallow continental margin structures offshore Mt Etna. In a similiar manner as observed onshore, the submarine realm is characterized by different blocks, which are controlled by local- and regional tectonics. We image a compressional regime at the toe of the continental margin, which is bound to an asymmetric basin system confining the eastward movement of the flank. In addition, we constrain the proposed southern boundary of the moving flank, which is identified as a right lateral oblique fault movement north of Catania Canyon. From our findings, we consider a major coupled volcano edifice instability and continental margin gravitational collapse and spreading to be present at Mt Etna, as we see a clear link between on- and offshore tectonic structures across the entire eastern flank. The new findings will help to evaluate hazards and risks accompanied by Mt Etna's slope- and continental margin instability and will be used as a base for future investigations in this region.

  4. High-resolution ERP mapping of cortical activation related to implicit object-location memory.

    PubMed

    Murphy, Jonathan S; Wynne, Ciara E; O'Rourke, Edel M; Commins, Seán; Roche, Richard A P

    2009-12-01

    High-density event-related potentials (ERPs) were recorded during an object recognition task which involved task-irrelevant changes in the location of studied objects. Participants categorised objects as studied or novel while data were analysed to ascertain the effect of the location changes on performance and waveform topography. Our results indicate that humans can classify objects faster and more accurately when using implicit spatial memory. Individual differences observed in object recognition proficiency were absent if objects were presented in their 'correct' location. In a second experiment we replicated the behavioural findings while manipulating viewpoint to discount scene recognition as an underlying factor. We propose a model which includes activation of the right medial temporal lobe prior to P300 elicitation to account for the prophylactic effect of implicit processing on object recognition. Hemispheric differences in parietal componentry dependant on sex of participant were also observed and are discussed in relation to differential strategies.

  5. Adrenal cortical responses to high-intensity, short rest, resistance exercise in men and women.

    PubMed

    Szivak, Tunde K; Hooper, David R; Dunn-Lewis, Courtenay; Comstock, Brett A; Kupchak, Brian R; Apicella, Jenna M; Saenz, Catherine; Maresh, Carl M; Denegar, Craig R; Kraemer, William J

    2013-03-01

    Commercial high-intensity, short rest (HI/SR) protocols have been anecdotally postured to be extremely demanding. However, limited prior studies have demonstrated HI/SR protocols to produce hyperreactions in metabolic and adrenal function; thus, the purpose of this study was to evaluate the physiological effects of an acute, high-intensity (75% 1-repetition maximum), short rest resistance exercise protocol. Nine trained men (age: 23.5 ± 3.5 years, height: 172.4 ± 4.0 cm, weight: 77.8 ± 8.8 kg) and 9 trained women (age: 22.9 ± 2.0 years, height: 168.4 ± 9.4 cm, weight: 68.5 ± 10.4 kg) participated in the HI/SR protocol, which consisted of a descending pyramid scheme of back squat, bench press, and deadlift, beginning with 10 repetitions of each, then 9, then 8, and so on until 1 repetition on the final set. Significant time effects were observed in lactate (immediate post [IP], +15, +60) and cortisol (IP, +15, +60) response. Significant sex effects were observed in lactate response (IP, +15) but not in cortisol response. Total work was higher in men and influenced magnitude of increase in lactate but not cortisol. No significant sex differences were noted in time to completion, average relative intensity, heart rate response or rating of perceived exertion scores. Highest lactate (IP men: 17.3 mmol·L(-1); IP women: 13.8 mmol·L(-1)) and cortisol (+15 men: 1,860.2 nmol·L(-1); +15 women: 1,831.7 nmol·L(-1)) values were considerably greater than those produced in typical resistance exercise programs, confirming that relative intensity and rest period length are important factors determining magnitude of metabolic and adrenal stress. Practical applications for the coach include cautious implementation of HI/SR protocols, as long-term sequential use may promote overtraining. A gradual reduction in rest interval length with concurrent gradual increase in intensity should be used to minimize potential negative effects such as nonfunctional overreaching.

  6. Changes in cortical activity measured with EEG during a high-intensity cycling exercise

    PubMed Central

    Cortese, Filomeno; Maurer, Christian; Baltich, Jennifer; Protzner, Andrea B.; Nigg, Benno M.

    2015-01-01

    This study investigated the effects of a high-intensity cycling exercise on changes in spectral and temporal aspects of electroencephalography (EEG) measured from 10 experienced cyclists. Cyclists performed a maximum aerobic power test on the first testing day followed by a time-to-exhaustion trial at 85% of their maximum power output on 2 subsequent days that were separated by ∼48 h. EEG was recorded using a 64-channel system at 500 Hz. Independent component (IC) analysis parsed the EEG scalp data into maximal ICs. An equivalent current dipole model was calculated for each IC, and results were clustered across subjects. A time-frequency analysis of the identified electrocortical clusters was performed to investigate the magnitude and timing of event-related spectral perturbations. Significant changes (P < 0.05) in electrocortical activity were found in frontal, supplementary motor and parietal areas of the cortex. Overall, there was a significant increase in EEG power as fatigue developed throughout the exercise. The strongest increase was found in the frontal area of the cortex. The timing of event-related desynchronization within the supplementary motor area corresponds with the onset of force production and the transition from flexion to extension in the pedaling cycle. The results indicate an involvement of the cerebral cortex during the pedaling task that most likely involves executive control function, as well as motor planning and execution. PMID:26538604

  7. Changes in cortical activity measured with EEG during a high-intensity cycling exercise.

    PubMed

    Enders, Hendrik; Cortese, Filomeno; Maurer, Christian; Baltich, Jennifer; Protzner, Andrea B; Nigg, Benno M

    2016-01-01

    This study investigated the effects of a high-intensity cycling exercise on changes in spectral and temporal aspects of electroencephalography (EEG) measured from 10 experienced cyclists. Cyclists performed a maximum aerobic power test on the first testing day followed by a time-to-exhaustion trial at 85% of their maximum power output on 2 subsequent days that were separated by ∼48 h. EEG was recorded using a 64-channel system at 500 Hz. Independent component (IC) analysis parsed the EEG scalp data into maximal ICs. An equivalent current dipole model was calculated for each IC, and results were clustered across subjects. A time-frequency analysis of the identified electrocortical clusters was performed to investigate the magnitude and timing of event-related spectral perturbations. Significant changes (P < 0.05) in electrocortical activity were found in frontal, supplementary motor and parietal areas of the cortex. Overall, there was a significant increase in EEG power as fatigue developed throughout the exercise. The strongest increase was found in the frontal area of the cortex. The timing of event-related desynchronization within the supplementary motor area corresponds with the onset of force production and the transition from flexion to extension in the pedaling cycle. The results indicate an involvement of the cerebral cortex during the pedaling task that most likely involves executive control function, as well as motor planning and execution. Copyright © 2016 the American Physiological Society.

  8. High-fidelity optical excitation of cortico-cortical projections at physiological frequencies.

    PubMed

    Hass, Charles A; Glickfeld, Lindsey L

    2016-11-01

    Optogenetic activation of axons is a powerful approach for determining the synaptic properties and impact of long-range projections both in vivo and in vitro. However, because of the difficulty of measuring activity in axons, our knowledge of the reliability of optogenetic axonal stimulation has relied on data from somatic recordings. Yet, there are many reasons why activation of axons may not be comparable to cell bodies. Thus we have developed an approach to more directly assess the fidelity of optogenetic activation of axonal projections. We expressed opsins (ChR2, Chronos, or oChIEF) in the mouse primary visual cortex (V1) and recorded extracellular, pharmacologically isolated presynaptic action potentials in response to axonal activation in the higher visual areas. Repetitive stimulation of axons with ChR2 resulted in a 70% reduction in the fiber volley amplitude and a 60% increase in the latency at all frequencies tested (10-40 Hz). Thus ChR2 cannot reliably recruit axons during repetitive stimulation, even at frequencies that are reliable for somatic stimulation, likely due to pronounced channel inactivation at the high light powers required to evoke action potentials. By comparison, oChIEF and Chronos evoked photocurrents that inactivated minimally and could produce reliable axon stimulation at frequencies up to 60 Hz. Our approach provides a more direct and accurate evaluation of the efficacy of new optogenetic tools and has identified Chronos and oChIEF as viable tools to interrogate the synaptic and circuit function of long-range projections.

  9. Visualization of Cortical Dynamics

    NASA Astrophysics Data System (ADS)

    Grinvald, Amiram

    2003-03-01

    Recent progress in studies of cortical dynamics will be reviewed including the combination of real time optical imaging based on voltage sensitive dyes, single and multi- unit recordings, LFP, intracellular recordings and microstimulation. To image the flow of neuronal activity from one cortical site to the next, in real time, we have used optical imaging based on newly designed voltage sensitive dyes and a Fuji 128x 128 fast camera which we modified. A factor of 20-40 fold improvement in the signal to noise ratio was obtained with the new dye during in vivo imaging experiments. This improvements has facilitates the exploration of cortical dynamics without signal averaging in the millisecond time domain. We confirmed that the voltage sensitive dye signal indeed reflects membrane potential changes in populations of neurons by showing that the time course of the intracellular activity recorded intracellularly from a single neuron was highly correlated in many cases with the optical signal from a small patch of cortex recorded nearby. We showed that the firing of single cortical neurons is not a random process but occurs when the on-going pattern of million of neurons is similar to the functional architecture map which correspond to the tuning properties of that neuron. Chronic optical imaging, combined with electrical recordings and microstimulation, over a long period of times of more than a year, was successfully applied also to the study of higher brain functions in the behaving macaque monkey.

  10. Cortical Visual Impairment

    MedlinePlus

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Cortical Visual Impairment En Español Read in Chinese What is cortical visual impairment? Cortical visual impairment (CVI) is a decreased ...

  11. High cardiorespiratory fitness in early to late middle age preserves the cortical circuitry associated with brain-heart integration during volitional exercise.

    PubMed

    Wood, Katelyn N; Luchyshyn, Torri A; Shoemaker, J Kevin

    2017-04-01

    This study tested the hypothesis that high cardiorespiratory fitness (peak oxygen uptake) preserves the cortical circuitry associated with cardiac arousal during exercise in middle- to older-aged individuals. Observations of changes in heart rate (HR) and in cortical blood oxygenation level-dependent (BOLD) images were made in 52 healthy, active individuals (45-73 yr; 16 women, 36 men) across a range of fitness (26-66 ml·kg(-1)·min(-1)). Seven repeated bouts of isometric handgrip (IHG) at 40% maximal voluntary contraction force were performed with functional magnetic resonance imaging at 3 T, with each contraction lasting 20 s and separated by 40 s of rest. HR responses to IHG showed high variability across individuals. Linear regression revealed that cardiorespiratory fitness was not a strong predictor of the HR response (r(2) = 0.09). In a region-of-interest analysis both the IHG task and the HR time course correlated with increased cortical activation in the bilateral insula and decreased activation relative to baseline in the anterior and posterior cingulate and medial prefrontal cortex (MPFC). t-Test results revealed greater deactivation at the MPFC with higher fitness levels beyond that of guideline-based activity. Therefore, whereas high cardiorespiratory fitness failed to affect absolute HR responses to IHG in this age range, a select effect was observed in cortical regions known to be associated with cardiovascular arousal.NEW & NOTEWORTHY Our first observation suggests that fitness does not strongly predict the heart rate (HR) response to a volitional handgrip task in middle- to older-aged adults. Second, the BOLD response associated with the handgrip task, and with the HR time course, was associated with response patterns in the cortical autonomic network. Finally, whereas high cardiorespiratory fitness failed to affect absolute HR responses to isometric handgrip in this age range, a select effect was observed in cortical regions known to be

  12. Tectonic, magmatic, and hydrothermal processes imaged by high-resolution seismicity beneath the fast-spreading East Pacific Rise (Invited)

    NASA Astrophysics Data System (ADS)

    Waldhauser, F.; Tolstoy, M.

    2010-12-01

    Cross-correlation and double-difference earthquake relocation methods have produced hypocenter locations with unprecedented resolution at many different scales and locations. The new locations typically image fine-scale seismogenic structures that help address important seismological and plate tectonic questions. In this paper we present results from a worldwide unique data set of more than 300,000 micro-earthquakes recorded at a dense OBS array (4x4 km) located on the fast-spreading East Pacific Rise at 9°50’ N. The array captured the build up of seismicity leading to a sea floor eruption in January 2006. We focus on improved relocations of ~16,000 earthquakes recorded during the first deployment between October 2003 and April 2004. An initial double-difference analysis using only analyst picks revealed the general structure of an along-axis oriented hydrothermal circulation cell, with an inferred down-flow zone near a 4th-order axial discontinuity and a cracking front overlying the axial magma chamber (AMC). To gain further insight into the detailed structure and kinematics of this divergent plate boundary we have increased the precision in event location by including cross-correlation delay times and improving relocation procedures that harness the high event density. We find that the majority of events within the down flow pipe represent frictional slip on short faults caused by regional tectonic stresses and thermal contraction as the cold sea water enters the hot crust. Along the eastern side of the ridge axis, just above the AMC at ~1.4 km depth, we observe repeated shear failure along well defined steeply east dipping structures. Composite first motion focal mechanisms for these strongly correlated events indicate reverse motion, suggesting that slip on these faults is caused by AMC inflation and associated injection of magma into a narrow sill. A broader sill appears to have formed at the bottom of the upflow zone beneath the active hydrothermal vents

  13. Highly impregnated slow-spread lithosphere : microstructure and geochemistry of olivine-rich troctolites from IODP Hole U1309D

    NASA Astrophysics Data System (ADS)

    Ildefonse, B.; Drouin, M.; Godard, M.

    2009-04-01

    IODP Expeditions 304-305 sampled the Atlantis Massif, an oceanic core complex located at 30°N in the inside corner of the intersection of the Mid-Atlantic Ridge with the Atlantis Fracture Zone. IODP Hole U1309D was drilled to 1415.5 meters below seafloor; it is the second deepest hole in slow-spreading crust, after Ocean Drilling Program (ODP) Hole 735B on the Southwest Indian Ridge. The recovered rocks are mostly gabbroic. We present a petrostructural (EBSD) and in-situ geochemical (EPMA, LA-ICPMS and LA-HR-ICPMS) study of olivine-rich troctolites (ol > 70%; 5.5 % of recovered section) and associated gabbros. Olivine-rich troctolites from Hole U1309D display poikilitic textures, with olivine ranging from coarse-grained subhedral crystals to medium-grained rounded crystals, embedded in large, undeformed clinopyroxene and plagioclase poikiloblasts. Trace element compositions of clinopyroxene and plagioclase poikiloblasts indicate that they crystallized from the same depleted MORB melt in both olivine-rich troctolites and associated gabbros. Olivine trace element compositions appear too depleted in light REE to be in equilibrium with plagioclase and clinopyroxene. Olivine crystallographic preferred orientations are weak, and misorientations are consistent with deformation by dislocation creep with activation of the high-temperature (010) [100] slip system, commonly described in asthenospheric mantle. The fabrics also display a relatively strong uncommon [001] concentration that we interpret as resulting from abundant melt impregnation. The joint study of geochemical processes and microstructures in these rocks suggest a complex crystallization history in an open system with percolation of large volume of MORB-type melt that postdate olivine crystal-plastic deformation. Although the mantle origin of the olivine is difficult to demonstrate unequivocally, we propose that olivine-rich troctolites represent the ultimate residue of melt-mantle reaction processes. Our

  14. High-definition transcranial direct current stimulation to both primary motor cortices improves unimanual and bimanual dexterity.

    PubMed

    Pixa, Nils H; Steinberg, Fabian; Doppelmayr, Michael

    2017-03-16

    While most research on brain stimulation with transcranial direct current stimulation (tDCS) targets unimanual motor tasks, little is known about its effects on bimanual motor performance. This study aims to investigate the effects of tDCS on unimanual as well as bimanual motor dexterity. We examined the effects of bihemispheric anodal high-definition tDCS (HD-atDCS) on both primary motor cortices (M1) applied concurrent with unimanual and bimanual motor training. We then measured the effects with the Purdue Pegboard Test (PPT) and compared them to a sham stimulation. Between a pretest and posttest, 31 healthy, right-handed participants practiced the PPT on three consecutive days and received - simultaneous to motor practice - either HD-atDCS over the left and right M1 (STIM, n=16) or a sham stimulation (SHAM, n=15). Five to seven days after the posttest, a follow-up test was conducted. Two-way ANOVAs with repeated measures showed significantly increased performance for all PPT-scores (p<0.001) in both groups. The scores for the right hand, both hands, and overall showed significant TIME x GROUP interactions (p<.05) with more improved performance for the STIM group, while left hand performance was not significantly altered. These effects were most pronounced in the follow-up test. Thus, we can conclude that a bihemispheric HD-atDCS of both M1's improves performance of unimanual and bimanual dexterity. The strength of the effects, however, depends on which hand is used in the unimanual task and the type of bimanual task performed.

  15. Conjugate volcanic rifted margins, seafloor spreading, and microcontinent: Insights from new high-resolution aeromagnetic surveys in the Norway Basin

    NASA Astrophysics Data System (ADS)

    Gernigon, Laurent; Blischke, Anett; Nasuti, Aziz; Sand, Morten

    2015-05-01

    We have acquired and processed new aeromagnetic data that cover the entire oceanic Norway Basin located between the Møre volcanic rifted margin and the Jan Mayen microcontinent (JMMC). The new compilation allows us to revisit the structure of the conjugate volcanic (rifted) margins and the spreading evolution of the Norway Basin from the Early Eocene breakup time to the Late Oligocene when the Aegir Ridge became extinct. The volcanic margins (in a strict sense) that formed before the opening of the Norway Basin have been disconnected with the previous Jurassic-Mid-Cretaceous episode of crustal thinning. We also show evidence of relationships between the margin architecture, the breakup magmatism distribution along the continent-oceanic transition, and the subsequent oceanic segmentation. The Norway Basin shows a complex system of asymmetric oceanic segments locally affected by episodic ridge jumps. The new aeromagnetic compilation also confirms that a fan-shaped spreading evolution of the Norway Basin was clearly active before the cessation of seafloor spreading and extinction of the Aegir Ridge. An important Mid-Eocene kinematic event at around magnetic chron C21r can be recognized in the Norway Basin. This event coincides with the onset of diking and increasing rifting activity (and possible oceanic accretion?) between the proto-JMMC and the East Greenland margin. It led to a second phase of breakup and microcontinent formation in the Norwegian-Greenland Sea ~26 Myrs later in the Oligocene.

  16. High-acceleration whole body vibration stimulates cortical bone accrual and increases bone mineral content in growing mice.

    PubMed

    Gnyubkin, Vasily; Guignandon, Alain; Laroche, Norbert; Vanden-Bossche, Arnaud; Malaval, Luc; Vico, Laurence

    2016-06-14

    Whole body vibration (WBV) is a promising tool for counteracting bone loss. Most WBV studies on animals have been performed at acceleration <1g and frequency between 30 and 90Hz. Such WBV conditions trigger bone growth in osteopenia models, but not in healthy animals. In order to test the ability of WBV to promote osteogenesis in young animals, we exposed seven-week-old male mice to vibration at 90Hz and 2g peak acceleration for 15min/day, 5 days/week. We examined the effects on skeletal tissues with micro-computed tomography and histology. We also quantified bone vascularization and mechanosensitive osteocyte proteins, sclerostin and DMP1. Three weeks of WBV resulted in an increase of femur cortical thickness (+5%) and area (+6%), associated with a 25% decrease of sclerostin expression, and 35% increase of DMP1 expression in cortical osteocytes. Mass-structural parameters of trabecular bone were unaltered in femur or vertebra, while osteoclastic parameters and bone formation rate were increased at both sites. Three weeks of WBV resulted in higher blood vessel numbers (+23%) in the distal femoral metaphysis. After 9-week WBV, we have not observed the difference in structural cortical or trabecular parameters. However, the tissue mineral density of cortical bone was increased by 2.5%. Three or nine weeks of 2g/90Hz WBV treatment did not affect longitudinal growth rate or body weight increase under our experimental conditions, indicating that these are safe to use. These results validate a potential of 2g/90Hz WBV to stimulate trabecular bone cellular activity, accelerate cortical bone growth, and increase bone mineral density. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Non-invasive predictors of human cortical bone mechanical properties: T(2)-discriminated H NMR compared with high resolution X-ray.

    PubMed

    Horch, R Adam; Gochberg, Daniel F; Nyman, Jeffry S; Does, Mark D

    2011-01-21

    Recent advancements in magnetic resonance imaging (MRI) have enabled clinical imaging of human cortical bone, providing a potentially powerful new means for assessing bone health with molecular-scale sensitivities unavailable to conventional X-ray-based diagnostics. To this end, (1)H nuclear magnetic resonance (NMR) and high-resolution X-ray signals from human cortical bone samples were correlated with mechanical properties of bone. Results showed that (1)H NMR signals were better predictors of yield stress, peak stress, and pre-yield toughness than were the X-ray derived signals. These (1)H NMR signals can, in principle, be extracted from clinical MRI, thus offering the potential for improved clinical assessment of fracture risk.

  18. Pain catastrophizing and cortical responses in amputees with varying levels of phantom limb pain: a high-density EEG brain-mapping study.

    PubMed

    Vase, Lene; Egsgaard, Line Lindhardt; Nikolajsen, Lone; Svensson, Peter; Jensen, Troels Staehelin; Arendt-Nielsen, Lars

    2012-05-01

    Pain catastrophizing has been associated with phantom limb pain, but so far the cortical processes and the brain regions involved in this relationship have not been investigated. It was therefore tested whether catastrophizing was related to (1) spontaneous pain, (2) somatosensory activity and (3) cortical responses in phantom limb pain patients. The cortical responses were investigated via electroencephalography (EEG) as it has a high temporal resolution which may be ideal for investigating especially the attentional and hypervigilance aspect of catastrophizing to standardized acute stimuli. Eighteen upper limb amputees completed the pain catastrophizing scale. Patients' spontaneous pain levels (worst and average pain, numerical rating scales) and thresholds to electrical stimulation (sensory detection and VRS2: intense but not painful) were determined. Non-painful electrical stimuli were applied to both the affected and non-affected arm, while high-resolution (128 channels) EEG signals were recorded. Catastrophizing accounted for significant amounts of the variance in relation to spontaneous pain, especially worst pain (64.1%), and it was significantly associated with thresholds. At the affected side, catastrophizing was significantly related to the power RMS of the N/P135 dipole located in the area around the secondary somatosensory cortex which has been shown to be associated with arousal and expectations. These findings corroborate the attentional model of pain catastrophizing by indicating that even non-painful stimuli are related to enhanced attention to and negative expectations of stimuli, and they suggest that memory processes may be central to understanding the link between catastrophizing and pain.

  19. High Precision and Fast Functional Mapping of Cortical Circuitry Through a Novel Combination of Voltage Sensitive Dye Imaging and Laser Scanning Photostimulation

    PubMed Central

    Olivas, Nicholas D.; Levi, Rafael; Ikrar, Taruna; Nenadic, Zoran

    2010-01-01

    The development of modern neuroscience tools is critical for deciphering brain circuit organization and function. An important aspect for technical development is to enhance each technique's advantages and compensate for limitations. We developed a high-precision and fast functional mapping technique in brain slices that incorporates the spatial precision of activation that can be achieved by laser-scanning photostimulation with rapid and high-temporal resolution assessment of evoked network activity that can be achieved by voltage-sensitive dye imaging. Unlike combination of whole cell recordings with photostimulation for mapping local circuit inputs to individually recorded neurons, this innovation is a new photostimulation-based technique to map cortical circuit output and functional connections at the level of neuronal populations. Here we report on this novel technique in detail and show its effective applications in mapping functional connections and circuit dynamics in mouse primary visual cortex and hippocampus. Given that this innovation enables rapid mapping and precise evaluation of cortical organization and function, it can have broad impacts in the field of cortical circuitry. PMID:20130040

  20. The high bone mass phenotype is characterised by a combined cortical and trabecular bone phenotype: findings from a pQCT case-control study.

    PubMed

    Gregson, Celia L; Sayers, Adrian; Lazar, Victor; Steel, Sue; Dennison, Elaine M; Cooper, Cyrus; Smith, George Davey; Rittweger, Jörn; Tobias, Jon H

    2013-01-01

    High bone mass (HBM), detected in 0.2% of DXA scans, is characterised by a mild skeletal dysplasia largely unexplained by known genetic mutations. We conducted the first systematic assessment of the skeletal phenotype in unexplained HBM using pQCT in our unique HBM population identified from screening routine UK NHS DXA scans. pQCT measurements from the mid and distal tibia and radius in 98 HBM cases were compared with (i) 65 family controls (constituting unaffected relatives and spouses), and (ii) 692 general population controls. HBM cases had substantially greater trabecular density at the distal tibia (340 [320, 359] mg/cm(3)), compared to both family (294 [276, 312]) and population controls (290 [281, 299]) (p<0.001 for both, adjusted for age, gender, weight, height, alcohol, smoking, malignancy, menopause, steroid and estrogen replacement use). Similar results were obtained at the distal radius. Greater cortical bone mineral density (cBMD) was observed in HBM cases, both at the midtibia and radius (adjusted p<0.001). Total bone area (TBA) was higher in HBM cases, at the distal and mid tibia and radius (adjusted p<0.05 versus family controls), suggesting greater periosteal apposition. Cortical thickness was increased at the mid tibia and radius (adjusted p<0.001), implying reduced endosteal expansion. Together, these changes resulted in greater predicted cortical strength (strength strain index [SSI]) in both tibia and radius (p<0.001). We then examined relationships with age; tibial cBMD remained constant with increasing age amongst HBM cases (adjusted β -0.01 [-0.02, 0.01], p=0.41), but declined in family controls (-0.05 [-0.03, -0.07], p<0.001) interaction p=0.002; age-related changes in tibial trabecular BMD, CBA and SSI were also divergent. In contrast, at the radius HBM cases and controls showed parallel age-related declines in cBMD and trabecular BMD. HBM is characterised by increased trabecular BMD and by alterations in cortical bone density and

  1. Consequences for selected high-elevation butterflies and moths from the spread of Pinus mugo into the alpine zone in the High Sudetes Mountains

    PubMed Central

    Šipoš, Jan; Kindlmann, Pavel; Kuras, Tomáš

    2016-01-01

    Due to changes in the global climate, isolated alpine sites have become one of the most vulnerable habitats worldwide. The indigenous fauna in these habitats is threatened by an invasive species, dwarf pine (Pinus mugo), which is highly competitive and could be important in determining the composition of the invertebrate community. In this study, the association of species richness and abundance of butterflies with the extent of Pinus mugo cover at individual alpine sites was determined. Butterflies at alpine sites in the High Sudetes Mountains (Mts.) were sampled using Moericke yellow water traps. The results of a Canonical Correspondence Analysis (CCA) indicated that at a local scale the area of alpine habitats is the main limiting factor for native species of alpine butterflies. Butterfly assemblages are associated with distance to the tree-line with the optimum situated in the lower forest zone. In addition the CCA revealed that biotic factors (i.e. Pinus mugo and alpine tundra vegetation) accounted for a significant amount of the variability in species data. Regionally, the CCA identified that the species composition of butterflies and moths is associated with presence and origin of Pinus mugo. Our study provides evidence that the structure of the Lepidopteran fauna that formed during the postglacial period and also the present composition of species assemblages is associated with the presence of Pinus mugo. With global warming, Pinus mugo has the potential to spread further into alpine areas and negatively affect the local species communities. PMID:27330857

  2. Consequences for selected high-elevation butterflies and moths from the spread of Pinus mugo into the alpine zone in the High Sudetes Mountains.

    PubMed

    Bílá, Karolína; Šipoš, Jan; Kindlmann, Pavel; Kuras, Tomáš

    2016-01-01

    Due to changes in the global climate, isolated alpine sites have become one of the most vulnerable habitats worldwide. The indigenous fauna in these habitats is threatened by an invasive species, dwarf pine (Pinus mugo), which is highly competitive and could be important in determining the composition of the invertebrate community. In this study, the association of species richness and abundance of butterflies with the extent of Pinus mugo cover at individual alpine sites was determined. Butterflies at alpine sites in the High Sudetes Mountains (Mts.) were sampled using Moericke yellow water traps. The results of a Canonical Correspondence Analysis (CCA) indicated that at a local scale the area of alpine habitats is the main limiting factor for native species of alpine butterflies. Butterfly assemblages are associated with distance to the tree-line with the optimum situated in the lower forest zone. In addition the CCA revealed that biotic factors (i.e. Pinus mugo and alpine tundra vegetation) accounted for a significant amount of the variability in species data. Regionally, the CCA identified that the species composition of butterflies and moths is associated with presence and origin of Pinus mugo. Our study provides evidence that the structure of the Lepidopteran fauna that formed during the postglacial period and also the present composition of species assemblages is associated with the presence of Pinus mugo. With global warming, Pinus mugo has the potential to spread further into alpine areas and negatively affect the local species communities.

  3. A characterization of intermediate-scale spread F structure from four years of high-resolution C/NOFS satellite data

    NASA Astrophysics Data System (ADS)

    Rino, Charles L.; Carrano, Charles S.; Groves, Keith M.; Roddy, Patrick A.

    2016-06-01

    Power law spectra have been invoked to interpret equatorial scintillation data for decades. Published analyses of intensity and phase scintillation data typically report power law spectra of the form q-p with 2.4 < p < 2.6. However, in situ rocket and satellite measurements of equatorial spread F have shown evidence of spectra with two power law components. Strong scatter simulations and recent theoretical results have shown that two-component power law spectra can reconcile simultaneous equatorial scintillation observations from VHF to S-Band. The Communication/Navigation Outage Forecasting System (C/NOFS) satellite Planar Langmuir Probe generated a multiyear high-resolution sampling of equatorial spread F, but published analyses to date have reported only single-component power laws over scales from tens of kilometers to 70 m. This paper summarizes the analysis of high-resolution C/NOFS data collected over the four year period 2011 to 2014. Following an earlier investigation of several months of C/NOFS data by the authors of this paper, the extended data set revealed a pattern of occurrence of two-component spectra in the most highly disturbed data sets. The results confirm a known inverse correlation between turbulent strength and spectral index. The new results are interpreted as an equatorial spread F life cycle pattern with two-component spectra in the early development phase giving way to single-component spectra in the decay phase.

  4. Ultra-high field MTR and qR2* differentiates subpial cortical lesions from normal-appearing gray matter in multiple sclerosis.

    PubMed

    Jonkman, Laura E; Fleysher, Lazar; Steenwijk, Martijn D; Koeleman, Jan A; de Snoo, Teun-Pieter; Barkhof, Frederik; Inglese, Matilde; Geurts, Jeroen Jg

    2016-09-01

    Cortical gray matter (GM) demyelination is frequent and clinically relevant in multiple sclerosis (MS). Quantitative magnetic resonance imaging (qMRI) sequences such as magnetization transfer ratio (MTR) and quantitative R2* (qR2*) can capture pathological subtleties missed by conventional magnetic resonance imaging (MRI) sequences. Although differences in MTR and qR2* have been reported between lesional and non-lesional tissue, differences between lesion types or lesion types and myelin density matched normal-appearing gray matter (NAGM) have not been found or investigated. Identify quantitative differences in histopathologically verified GM lesion types and matched NAGM at ultra-high field strength. Using 7T post-mortem MRI, MRI lesions were marked on T2 images and co-registered to the calculated MTR and qR2* maps for further evaluation. In all, 15 brain slices were collected, containing a total of 74 cortical GM lesions and 45 areas of NAGM. Intracortical lesions had lower MTR and qR2* values compared to NAGM. Type I lesions showed lower MTR than type III lesions. Type III lesions showed lower MTR than matched NAGM, and type I and IV lesions showed lower qR2* than matched NAGM. qMRI at 7T can provide additional information on extent of cortical pathology, especially concerning subpial lesions. This may be relevant for monitoring disease progression and potential treatment effects. © The Author(s), 2015.

  5. Different Mode of Afferents Determines the Frequency Range of High Frequency Activities in the Human Brain: Direct Electrocorticographic Comparison between Peripheral Nerve and Direct Cortical Stimulation.

    PubMed

    Kobayashi, Katsuya; Matsumoto, Riki; Matsuhashi, Masao; Usami, Kiyohide; Shimotake, Akihiro; Kunieda, Takeharu; Kikuchi, Takayuki; Mikuni, Nobuhiro; Miyamoto, Susumu; Fukuyama, Hidenao; Takahashi, Ryosuke; Ikeda, Akio

    2015-01-01

    Physiological high frequency activities (HFA) are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections), or different terminal layers (layer IV vs. layer II/III) affect its frequency, we, in the primary somatosensory cortex (SI), compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response) and N80 (late response) of somatosensory evoked potentials (HFA(SEP(N20)) and HFA(SEP(N80))) and compared those overriding N1 and N2 (first and second responses) of cortico-cortical evoked potentials (HFA(CCEP(N1)) and HFA(CCEP(N2))). HFA(SEP(N20)) showed the power peak in the frequency above 200 Hz, while HFA(CCEP(N1)) had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFA(CCEP(N1)) and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions.

  6. Different Mode of Afferents Determines the Frequency Range of High Frequency Activities in the Human Brain: Direct Electrocorticographic Comparison between Peripheral Nerve and Direct Cortical Stimulation

    PubMed Central

    Kobayashi, Katsuya; Matsumoto, Riki; Matsuhashi, Masao; Usami, Kiyohide; Shimotake, Akihiro; Kunieda, Takeharu; Kikuchi, Takayuki; Mikuni, Nobuhiro; Miyamoto, Susumu; Fukuyama, Hidenao; Takahashi, Ryosuke; Ikeda, Akio

    2015-01-01

    Physiological high frequency activities (HFA) are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections), or different terminal layers (layer IV vs. layer II/III) affect its frequency, we, in the primary somatosensory cortex (SI), compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response) and N80 (late response) of somatosensory evoked potentials (HFASEP(N20) and HFASEP(N80)) and compared those overriding N1 and N2 (first and second responses) of cortico-cortical evoked potentials (HFACCEP(N1) and HFACCEP(N2)). HFASEP(N20) showed the power peak in the frequency above 200 Hz, while HFACCEP(N1) had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFACCEP(N1) and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions. PMID:26087042

  7. Rapid conversion of an oceanic spreading center to a subduction zone inferred from high-precision geochronology

    NASA Astrophysics Data System (ADS)

    Keenan, Timothy E.; Encarnación, John; Buchwaldt, Robert; Fernandez, Dan; Mattinson, James; Rasoazanamparany, Christine; Luetkemeyer, P. Benjamin

    2016-11-01

    Where and how subduction zones initiate is a fundamental tectonic problem, yet there are few well-constrained geologic tests that address the tectonic settings and dynamics of the process. Numerical modeling has shown that oceanic spreading centers are some of the weakest parts of the plate tectonic system [Gurnis M, Hall C, Lavier L (2004) Geochem Geophys Geosys 5:Q07001], but previous studies have not favored them for subduction initiation because of the positive buoyancy of young lithosphere. Instead, other weak zones, such as fracture zones, have been invoked. Because these models differ in terms of the ages of crust that are juxtaposed at the site of subduction initiation, they can be tested by dating the protoliths of metamorphosed oceanic crust that is formed by underthrusting at the beginning of subduction and comparing that age with the age of the overlying lithosphere and the timing of subduction initiation itself. In the western Philippines, we find that oceanic crust was less than ˜1 My old when it was underthrust and metamorphosed at the onset of subduction in Palawan, Philippines, implying forced subduction initiation at a spreading center. This result shows that young and positively buoyant, but weak, lithosphere was the preferred site for subduction nucleation despite the proximity of other potential weak zones with older, denser lithosphere and that plate motion rapidly changed from divergence to convergence.

  8. Rapid conversion of an oceanic spreading center to a subduction zone inferred from high-precision geochronology.

    PubMed

    Keenan, Timothy E; Encarnación, John; Buchwaldt, Robert; Fernandez, Dan; Mattinson, James; Rasoazanamparany, Christine; Luetkemeyer, P Benjamin

    2016-11-22

    Where and how subduction zones initiate is a fundamental tectonic problem, yet there are few well-constrained geologic tests that address the tectonic settings and dynamics of the process. Numerical modeling has shown that oceanic spreading centers are some of the weakest parts of the plate tectonic system [Gurnis M, Hall C, Lavier L (2004) Geochem Geophys Geosys 5:Q07001], but previous studies have not favored them for subduction initiation because of the positive buoyancy of young lithosphere. Instead, other weak zones, such as fracture zones, have been invoked. Because these models differ in terms of the ages of crust that are juxtaposed at the site of subduction initiation, they can be tested by dating the protoliths of metamorphosed oceanic crust that is formed by underthrusting at the beginning of subduction and comparing that age with the age of the overlying lithosphere and the timing of subduction initiation itself. In the western Philippines, we find that oceanic crust was less than ∼1 My old when it was underthrust and metamorphosed at the onset of subduction in Palawan, Philippines, implying forced subduction initiation at a spreading center. This result shows that young and positively buoyant, but weak, lithosphere was the preferred site for subduction nucleation despite the proximity of other potential weak zones with older, denser lithosphere and that plate motion rapidly changed from divergence to convergence.

  9. Rapid conversion of an oceanic spreading center to a subduction zone inferred from high-precision geochronology

    PubMed Central

    Keenan, Timothy E.; Encarnación, John; Buchwaldt, Robert; Fernandez, Dan; Mattinson, James; Rasoazanamparany, Christine; Luetkemeyer, P. Benjamin

    2016-01-01

    Where and how subduction zones initiate is a fundamental tectonic problem, yet there are few well-constrained geologic tests that address the tectonic settings and dynamics of the process. Numerical modeling has shown that oceanic spreading centers are some of the weakest parts of the plate tectonic system [Gurnis M, Hall C, Lavier L (2004) Geochem Geophys Geosys 5:Q07001], but previous studies have not favored them for subduction initiation because of the positive buoyancy of young lithosphere. Instead, other weak zones, such as fracture zones, have been invoked. Because these models differ in terms of the ages of crust that are juxtaposed at the site of subduction initiation, they can be tested by dating the protoliths of metamorphosed oceanic crust that is formed by underthrusting at the beginning of subduction and comparing that age with the age of the overlying lithosphere and the timing of subduction initiation itself. In the western Philippines, we find that oceanic crust was less than ∼1 My old when it was underthrust and metamorphosed at the onset of subduction in Palawan, Philippines, implying forced subduction initiation at a spreading center. This result shows that young and positively buoyant, but weak, lithosphere was the preferred site for subduction nucleation despite the proximity of other potential weak zones with older, denser lithosphere and that plate motion rapidly changed from divergence to convergence. PMID:27821756

  10. Plume Flux, Spreading Rate, and Obliquity of Seafloor Spreading

    NASA Astrophysics Data System (ADS)

    Zhang, T.; Gordon, R. G.

    2016-12-01

    Most of Earth's surface is created by seafloor spreading, a fundamental global tectonic process. While most seafloor spreading is orthogonal, i.e., the strike of mid-ocean ridge (MOR) segments is perpendicular to transform faults, obliquity of up to 45° occurs. Here, building on the work of DeMets et al. [2010] we investigate the global relationship between obliquity of seafloor spreading, spreading rates, and the flux of nearby plumes. While we confirm the well-known tendency for obliquity to decrease with increasing spreading rate [Atwater and Macdonald, 1977], we find exceptions at both intermediate (up to 18°) and ultra-fast (up to 12°) rates of spreading. Thus, factors other than the minimization of power dissipation across mid-ocean ridges and transform faults [Stein, 1978] may influence the amount of obliquity. Abelson & Agnon [1997] modeled spreading centers as fluid-filled cracks and found that the variation of segment orientation depends on the ratio of the magma overpressure to the remote tectonic tension that drives plate separation. A high ratio promotes oblique spreading and a low ratio promotes segmentation that results in orthogonal spreading. They further argued that if a hotspot lies near a MOR segment, the hotspot contributes to magma overpressure along the segment. We quantify their argument as follows: (1) that magma overpressure increases with increasing flux of a plume. (2) that effective magma overpressure decreases with increasing distance between a MOR segment and a plume. From this we estimate the effective plume flux delivered to each mid-ocean ridge using published plume flux estimates. Not only does obliquity tend to decrease with increasing spreading rate, but also it tends to increase with increasing effective plume flux delivered to a MOR segment. Many exceptions occur, however. Along slow spreading centers, many segments are less oblique than along the Reykjanes Ridge and western Gulf of Aden despite having higher effective

  11. High Definition Transcranial Direct Current Stimulation Induces Both Acute and Persistent Changes in Broadband Cortical Synchronization: a Simultaneous tDCS-EEG Study

    PubMed Central

    Roy, Abhrajeet; Baxter, Bryan

    2014-01-01

    The goal of this study was to develop methods for simultaneously acquiring electrophysiological data during high definition transcranial direct current stimulation (tDCS) using high resolution electroencephalography (EEG). Previous studies have pointed to the after effects of tDCS on both motor and cognitive performance, and there appears to be potential for using tDCS in a variety of clinical applications. However, little is known about the real-time effects of tDCS on rhythmic cortical activity in humans due to the technical challenges of simultaneously obtaining electrophysiological data during ongoing stimulation. Furthermore, the mechanisms of action of tDCS in humans are not well understood. We have conducted a simultaneous tDCS-EEG study in a group of healthy human subjects. Significant acute and persistent changes in spontaneous neural activity and event related synchronization (ERS) were observed during and after the application of high definition tDCS over the left sensorimotor cortex. Both anodal and cathodal stimulation resulted in acute global changes in broadband cortical activity which were significantly different than the changes observed in response to sham stimulation. For the group of 8 subjects studied, broadband individual changes in spontaneous activity during stimulation were apparent both locally and globally. In addition, we found that high definition tDCS of the left sensorimotor cortex can induce significant ipsilateral and contralateral changes in event related desynchronization (ERD) and ERS during motor imagination following the end of the stimulation period. Overall, our results demonstrate the feasibility of acquiring high resolution EEG during high definition tDCS and provide evidence that tDCS in humans directly modulates rhythmic cortical synchronization during and after its administration. PMID:24956615

  12. High-definition transcranial direct current stimulation induces both acute and persistent changes in broadband cortical synchronization: a simultaneous tDCS-EEG study.

    PubMed

    Roy, Abhrajeet; Baxter, Bryan; He, Bin

    2014-07-01

    The goal of this study was to develop methods for simultaneously acquiring electrophysiological data during high-definition transcranial direct current stimulation (tDCS) using high-resolution electroencephalography (EEG). Previous studies have pointed to the after-effects of tDCS on both motor and cognitive performance, and there appears to be potential for using tDCS in a variety of clinical applications. However, little is known about the real-time effects of tDCS on rhythmic cortical activity in humans due to the technical challenges of simultaneously obtaining electrophysiological data during ongoing stimulation. Furthermore, the mechanisms of action of tDCS in humans are not well understood. We have conducted a simultaneous tDCS-EEG study in a group of healthy human subjects. Significant acute and persistent changes in spontaneous neural activity and event-related synchronization (ERS) were observed during and after the application of high-definition tDCS over the left sensorimotor cortex. Both anodal and cathodal stimulation resulted in acute global changes in broadband cortical activity which were significantly different than the changes observed in response to sham stimulation. For the group of eight subjects studied, broadband individual changes in spontaneous activity during stimulation were apparent both locally and globally. In addition, we found that high-definition tDCS of the left sensorimotor cortex can induce significant ipsilateral and contralateral changes in event-related desynchronization and ERS during motor imagination following the end of the stimulation period. Overall, our results demonstrate the feasibility of acquiring high-resolution EEG during high-definition tDCS and provide evidence that tDCS in humans directly modulates rhythmic cortical synchronization during and after its administration.

  13. Spatial and Temporal Spread of Acute Viral Respiratory Infections in Young Children Living in High-Altitude Rural Communities: A Prospective Household-Based Study

    PubMed Central

    Cherry, Charlotte Buehler; Griffin, Marie R.; Edwards, Kathryn M.; Williams, John V.; Gil, Ana I.; Verastegui, Hector; Lanata, Claudio F.; Grijalva, Carlos G

    2016-01-01

    Background Few studies have described patterns of transmission of viral acute respiratory infections (ARI) in children in developing countries. We examined the spatial and temporal spread of viral ARI among young children in rural Peruvian highland communities. Previous work has described intense social interactions in those communities, which could influence the transmission of viral infections. Methods We enrolled and followed children <3 years of age for detection of ARI during the 2009–2011 respiratory seasons in a rural setting with relatively wide geographic dispersion of households and communities. Viruses detected included influenza, respiratory syncytial virus (RSV), human metapneumovirus (MPV), and parainfluenza 2 and 3 viruses (PIV2; PIV3). We used geospatial analyses to identify specific viral infection hot spots with high ARI incidence. We also explored the local spread of ARI from index cases using standard deviational ellipses. Results Geospatial analyses revealed hot spots of high ARI incidence around the index cases of influenza outbreaks and RSV outbreak in 2010. Although PIV3 in 2009 and PIV2 in 2010 showed distinct spatial hot spots, clustering was not in proximity to their respective index cases. No significant aggregation around index cases was noted for other viruses. Standard deviational ellipse analyses suggested that influenza B and RSV in 2010, and MPV in 2011 spread temporally in alignment with the major road network. Conclusions Despite the geographic dispersion of communities in this rural setting, we observed a rapid spread of viral ARI among young children. Influenza strains and RSV in 2010 had distinctive outbreaks arising from their index cases. PMID:27404599

  14. Cortical Modulation of Motor Control Biofeedback among the Elderly with High Fall Risk during a Posture Perturbation Task with Augmented Reality.

    PubMed

    Chang, Chun-Ju; Yang, Tsui-Fen; Yang, Sai-Wei; Chern, Jen-Suh

    2016-01-01

    The cerebral cortex provides sensorimotor integration and coordination during motor control of daily functional activities. Power spectrum density based on electroencephalography (EEG) has been employed as an approach that allows an investigation of the spatial-temporal characteristics of neuromuscular modulation; however, the biofeedback mechanism associated with cortical activation during motor control remains unclear among elderly individuals. Thirty one community-dwelling elderly participants were divided into low fall-risk potential (LF) and high fall-risk potential (HF) groups based upon the results obtained from a receiver operating characteristic analysis of the ellipse area of the center of pressure. Electroencephalography (EEG) was performed while the participants stood on a 6-degree-of-freedom Stewart platform, which generated continuous perturbations and done either with or without the virtual reality scene. The present study showed that when there was visual stimulation and poor somatosensory coordination, a higher level of cortical response was activated in order to keep postural balance. The elderly participants in the LF group demonstrated a significant and strong correlation between postural-related cortical regions; however, the elderly individuals in the HF group did not show such a relationship. Moreover, we were able to clarify the roles of various brainwave bands functioning in motor control. Specifically, the gamma and beta bands in the parietal-occipital region facilitate the high-level cortical modulation and sensorimotor integration, whereas the theta band in the frontal-central region is responsible for mediating error detection during perceptual motor tasks. Finally, the alpha band is associated with processing visual challenges in the occipital lobe.With a variety of motor control demands, increment in brainwave band coordination is required to maintain postural stability. These investigations shed light on the cortical modulation of

  15. Cortical Modulation of Motor Control Biofeedback among the Elderly with High Fall Risk during a Posture Perturbation Task with Augmented Reality

    PubMed Central

    Chang, Chun-Ju; Yang, Tsui-Fen; Yang, Sai-Wei; Chern, Jen-Suh

    2016-01-01

    The cerebral cortex provides sensorimotor integration and coordination during motor control of daily functional activities. Power spectrum density based on electroencephalography (EEG) has been employed as an approach that allows an investigation of the spatial–temporal characteristics of neuromuscular modulation; however, the biofeedback mechanism associated with cortical activation during motor control remains unclear among elderly individuals. Thirty one community-dwelling elderly participants were divided into low fall-risk potential (LF) and high fall-risk potential (HF) groups based upon the results obtained from a receiver operating characteristic analysis of the ellipse area of the center of pressure. Electroencephalography (EEG) was performed while the participants stood on a 6-degree-of-freedom Stewart platform, which generated continuous perturbations and done either with or without the virtual reality scene. The present study showed that when there was visual stimulation and poor somatosensory coordination, a higher level of cortical response was activated in order to keep postural balance. The elderly participants in the LF group demonstrated a significant and strong correlation between postural-related cortical regions; however, the elderly individuals in the HF group did not show such a relationship. Moreover, we were able to clarify the roles of various brainwave bands functioning in motor control. Specifically, the gamma and beta bands in the parietal–occipital region facilitate the high-level cortical modulation and sensorimotor integration, whereas the theta band in the frontal–central region is responsible for mediating error detection during perceptual motor tasks. Finally, the alpha band is associated with processing visual challenges in the occipital lobe.With a variety of motor control demands, increment in brainwave band coordination is required to maintain postural stability. These investigations shed light on the cortical modulation

  16. High-affinity sites form an interaction network to facilitate spreading of the MSL complex across the X chromosome in Drosophila

    PubMed Central

    Ramirez, Fidel; Lingg, Thomas; Toscano, Sarah; Lam, Kin Chung; Georgiev, Plamen; Chung, Ho-Ryun; Lajoie, Bryan; de Wit, Elzo; Zhan, Ye; de Laat, Wouter; Dekker, Job; Manke, Thomas; Akhtar, Asifa

    2016-01-01

    Summary Dosage compensation mechanisms provide a paradigm to study the contribution of chromosomal conformation towards targeting and spreading of epigenetic regulators over a specific chromosome. By using Hi-C and 4C analyses we show that high-affinity sites (HAS), landing platforms of the male-specific lethal (MSL) complex, are enriched around topologically associating domain (TAD) boundaries on the X chromosome and harbor more long-range contacts in a sex-independent manner. Ectopically expressed roX1 and roX2 RNA target HAS on the X chromosome in trans and, via spatial proximity, induce spreading of the MSL complex in cis, leading to increased expression of neighboring autosomal genes. We show that the MSL complex regulates nucleosome positioning at HAS, thus acting locally rather than influencing the overall chromosomal architecture. We propose that sex-independent three-dimensional conformation of the X chromosome poises it for exploitation by the MSL complex, thereby facilitating spreading in males. PMID:26431028

  17. The application of GIS and RS for epidemics: a case study of the spread of highly pathogenic avian influenza in China in 2004-2005

    NASA Astrophysics Data System (ADS)

    Zhong, Shaobo; Lan, Guiwen; Zhu, Haiguo; Wen, Renqiang; Zhao, Qiansheng; Huang, Quanyi

    2008-12-01

    Because of their inherent advantages, Geographic Information System (GIS) and Remote Sensing (RS) are extremely useful for dealing with geographically referenced information. In the study of epidemics, most data are geographically referenced, which makes GIS and RS the perfect even necessary tools for processing, analysis, representation of epidemic data. Comprehensively considering the data requirements in the study of highly pathogenic avian influenza (HPAI) coupled with the quality of the existing remotely sensed data in terms of the resolution of space, time and spectra, the data sensed by MODIS are chosen and the relevant methods and procedures of data processing from RS and GIS for some environmental factors are proposed. Through using spatial analysis functions and Exploratory Spatial Data Analysis (ESDA) of GIS, some results of relationship between HPAI occurrences and these potential factors are presented. The role played by bird migration is also preliminarily illustrated with some operations such as visualization, overlapping etc. provided by GIS. Through the work of this paper, we conclude: Firstly, the migration of birds causes the spread of HPAI all over the country in 2004-2005. Secondly, the migration of birds is the reason why the spread of HPAI is perturbed. That is, for some classic communicable diseases, their spread exhibits obvious spatial diffusion process. However, the spread of HPAI breaks this general rule. We think leap diffusion and time lag are the probable reasons for this kind of phenomena. Potential distribution of HPAI viruses (corresponding to the distribution of flyways and putative risk sources) is not completely consistent with the occurrences of HPAI. For this phenomenon, we think, in addition to the flyways of birds, all kinds of geographical, climatic factors also have important effect on the occurrences of HPAI. Through the case study of HPAI, we can see that GIS and RS can play very important roles in the study of epidemics.

  18. Spreading of Nematic Liquid Crystals

    NASA Astrophysics Data System (ADS)

    Poulard, Christophe

    2004-11-01

    A cyanobiphenyl liquid crystal drop in the nematic phase should spread on a silicon wafer. In fact, the drop hardly spreads due to the strong antagonist anchoring on the substrate and at the free surface. In a humidity controlled box at high RH and on a hydrophilic substrate, the friction is considerably reduced and the drop spreads easily. A well defined instability develops at the contact line, with two characteristic wavelengths, associated with a modulation of the drop thickness. A theoretical analysis, made by M. Ben Amar and L. Cummings, allows to understand one of the wavelength by an elastic approach and gives a wavelength proportionnal to the local drop's thickness.

  19. Effect of auroral substorms on the ionospheric range spread-F enhancements at high southern midlatitudes using real time vertical-sounding ionograms

    NASA Astrophysics Data System (ADS)

    Hajkowicz, Lech A.

    2016-03-01

    A comprehensive study has been undertaken on the effect of magnetic substorm onsets (as deduced from the auroral hourly electrojet AE-index) on the occurrence of high midlatitude (or sub-auroral latitude) ionospheric range spread-F (Sr). Unlike the previous reports real-time ionograms were used in this analysis thus eliminating ambiguities stemming from the correlating secondary evidence of spread-F with auroral substorms. The Australian southernmost ionosonde station Hobart (51.6°S geom.) proved to be uniquely suitable for the task as being sufficiently close to the southern auroral zone. Sr was assigned in km to each hourly nighttime ionogram at two sounding frequencies: Sr1 (at 2 MHz) and Sr2 (at 6 MHz) for four months in 2002: January and June (representing southern summer and winter solstices), and March and September (representing autumn and vernal equinoxes). It is evident that the southern winter solstitial period (June) is associated with high endemic midlatitude spread-F activity. All other seasons are closely linked with temporal sequences of enhanced spread-F activity following substorm onsets. For the first time it was possible not only find a simultaneous occurrence pattern of these diverse phenomena but to deduce numerical characteristics of the response of midlatitude ionosphere to the global auroral stimulus. Excellent case events, hitherto unpublished, are shown illustrating the presence of the AE peaks (in nT) being ahead of Sr peaks (in km) by a time shift ∆t (in h). Sr1 magnitude showed a significant correlation with the magnitudes of the preceding AE with a correlation coefficient (r) of 0.51 (probability of the occurrence by chance less than 0.01). Sr2 peaks were more sensitive to auroral disturbances but were not correlated with the AE magnitude variations. The time shift (∆t) was on average 4 h with a standard deviation of 3 h. The general pattern in the occurrence of magnetic substorms and spread-F is very similar. A number of

  20. Invasion of Seawater-Derived Fluids at Very High Temperatures in the Oman Ophiolite - a Key for Cooling the Deep Crust at Fast-Spreading Ridges

    NASA Astrophysics Data System (ADS)

    Koepke, J.; Mueller, T.; Linsler, S.; Schuth, S.; Garbe-Schoenberg, C. D.; McCaig, A. M.

    2014-12-01

    Prominent conceptual models for the formation of the deep, fast-spread crust are the "gabbro-glacier" model, where the lower crust is formed in the axial melt lens, and the "sheeted sill" model, where the lower gabbros are generated by the intrusion of sills of gabbroic mushes. A requirement for the latter model is a substantial hydrothermal cooling of the oceanic crust in the depth, and as long as the "Rosetta stone" for the mechanism of this deep cooling is not found, the "sheeted sill" model and derivatives cannot be accepted as reliable option how the deep oceanic fast-spread crust is formed. In recent field campaigns for establishing a geochemical and petrological profile through typical fast-spreading oceanic crust in the Wadi Gideah (Wadi Tayin massif, Oman ophiolite), we discovered several, often more than 100 m wide fault zones, cutting a coherent series of layered gabbro at many places. These zones are characterized by pervasive alteration, mainly in greenschist and sub-greenschist facies. Isotope geochemical studies of these zones imply that these zones can be interpreted as pathways for channeled hydrothermal flux, in accord with observations of Coogan et al. (2006). In most of the fault zones, we observed the occurrence of varitextured hornblende gabbro, alternating with zones of former layered gabbros showing intense overgrowth of high- temperature amphibole, and sometimes with flasered amphibolites. The petrologic record implies fluid flux in the center of this zones at very high temperatures (≤ 1000°C), enabling even the production of hornblende gabbros by hydrous partial melting of layered gabbro, shielded by zones formed at high-temperature conditions (formation of high-T amphiboles) and at low-temperature conditions (greenschist facies rocks). First thermal modeling based on the petrological record of these zones are in progress. Coogan LA, Howard KA, Gillis KM, Bickle MJ, Chapman H, Boyce AJ, Jenkin GRT, Wilson RN (2006) Am. J. Sci. 306: 389-427

  1. Detection and quantification of regional cortical gray matter damage in multiple sclerosis utilizing gradient echo MRI.

    PubMed

    Wen, Jie; Yablonskiy, Dmitriy A; Luo, Jie; Lancia, Samantha; Hildebolt, Charles; Cross, Anne H

    2015-01-01

    Cortical gray matter (GM) damage is now widely recognized in multiple sclerosis (MS). The standard MRI does not reliably detect cortical GM lesions, although cortical volume loss can be measured. In this study, we demonstrate that the gradient echo MRI can reliably and quantitatively assess cortical GM damage in MS patients using standard clinical scanners. High resolution multi-gradient echo MRI was used for regional mapping of tissue-specific MRI signal transverse relaxation rate values (R2(*)) in 10 each relapsing-remitting, primary-progressive and secondary-progressive MS subjects. A voxel spread function method was used to correct artifacts induced by background field gradients. R2(*) values from healthy controls (HCs) of varying ages were obtained to establish baseline data and calculate ΔR2(*) values - age-adjusted differences between MS patients and HC. Thickness of cortical regions was also measured in all subjects. In cortical regions, ΔR2(*) values of MS patients were also adjusted for changes in cortical thickness. Symbol digit modalities (SDMT) and paced auditory serial addition (PASAT) neurocognitive tests, as well as Expanded Disability Status Score, 25-foot timed walk and nine-hole peg test results were also obtained on all MS subjects. We found that ΔR2(*) values were lower in multiple cortical GM and normal appearing white matter (NAWM) regions in MS compared with HC. ΔR2(*) values of global cortical GM and several specific cortical regions showed significant (p < 0.05) correlations with SDMT and PASAT scores, and showed better correlations than volumetric measures of the same regions. Neurological tests not focused on cognition (Expanded Disability Status Score, 25-foot timed walk and nine-hole peg tests) showed no correlation with cortical GM ΔR2(*) values. The technique presented here is robust and reproducible. It requires less than 10 min and can be implemented on any MRI scanner. Our results show that quantitative tissue-specific R2

  2. Trabecular and Cortical Bone of Growing C3H Mice Is Highly Responsive to the Removal of Weightbearing

    PubMed Central

    Judex, Stefan

    2016-01-01

    Genetic make-up strongly influences the skeleton’s susceptibility to the loss of weight bearing with some inbred mouse strains experiencing great amounts of bone loss while others lose bone at much smaller rates. At young adulthood, female inbred C3H/HeJ (C3H) mice are largely resistant to catabolic pressure induced by unloading. Here, we tested whether the depressed responsivity to unloading is inherent to the C3H genetic make-up or whether a younger age facilitates a robust skeletal response to unloading. Nine-week-old, skeletally immature, female C3H mice were subjected to 3wk of hindlimb unloading (HLU, n = 12) or served as normal baseline controls (BC, n = 10) or age-matched controls (AC, n = 12). In all mice, cortical and trabecular architecture of the femur, as well as levels of bone formation and resorption, were assessed with μCT, histomorphometry, and histology. Changes in bone marrow progenitor cell populations were determined with flow cytometry. Following 21d of unloading, HLU mice had 52% less trabecular bone in the distal femur than normal age-matched controls. Reflecting a loss of trabecular tissue compared to baseline controls, trabecular bone formation rates (BFR/BS) in HLU mice were 40% lower than in age-matched controls. Surfaces undergoing osteoclastic resorption were not significantly different between groups. In the mid-diaphysis, HLU inhibited cortical bone growth leading to 14% less bone area compared to age-matched controls. Compared to AC, BFR/BS of HLU mice were 53% lower at the endo-cortical surface and 49% lower at the periosteal surface of the mid-diaphysis. The enriched osteoprogenitor cell population (OPC) comprised 2% of the bone marrow stem cells in HLU mice, significantly different from 3% OPC in the AC group. These data show that bone tissue in actively growing C3H mice is lost rapidly, or fails to grow, during the removal of functional weight bearing—in contrast to the insignificant response previously demonstrated in

  3. Disease spread models to estimate highly uncertain emerging diseases losses for animal agriculture insurance policies: an application to the U.S. farm-raised catfish industry.

    PubMed

    Zagmutt, Francisco J; Sempier, Stephen H; Hanson, Terril R

    2013-10-01

    Emerging diseases (ED) can have devastating effects on agriculture. Consequently, agricultural insurance for ED can develop if basic insurability criteria are met, including the capability to estimate the severity of ED outbreaks with associated uncertainty. The U.S. farm-raised channel catfish (Ictalurus punctatus) industry was used to evaluate the feasibility of using a disease spread simulation modeling framework to estimate the potential losses from new ED for agricultural insurance purposes. Two stochastic models were used to simulate the spread of ED between and within channel catfish ponds in Mississippi (MS) under high, medium, and low disease impact scenarios. The mean (95% prediction interval (PI)) proportion of ponds infected within disease-impacted farms was 7.6% (3.8%, 22.8%), 24.5% (3.8%, 72.0%), and 45.6% (4.0%, 92.3%), and the mean (95% PI) proportion of fish mortalities in ponds affected by the disease was 9.8% (1.4%, 26.7%), 49.2% (4.7%, 60.7%), and 88.3% (85.9%, 90.5%) for the low, medium, and high impact scenarios, respectively. The farm-level mortality losses from an ED were up to 40.3% of the total farm inventory and can be used for insurance premium rate development. Disease spread modeling provides a systematic way to organize the current knowledge on the ED perils and, ultimately, use this information to help develop actuarially sound agricultural insurance policies and premiums. However, the estimates obtained will include a large amount of uncertainty driven by the stochastic nature of disease outbreaks, by the uncertainty in the frequency of future ED occurrences, and by the often sparse data available from past outbreaks. © 2013 Society for Risk Analysis.

  4. Cortical microtubule rearrangements and cell wall patterning

    PubMed Central

    Oda, Yoshihisa

    2015-01-01

    Plant cortical microtubules, which form a highly ordered array beneath the plasma membrane, play essential roles in determining cell shape and function by directing the arrangement of cellulosic and non-cellulosic compounds on the cell surface. Interphase transverse arrays of cortical microtubules self-organize through their dynamic instability and inter-microtubule interactions, and by branch-form microtubule nucleation and severing. Recent studies revealed that distinct spatial signals including ROP GTPase, cellular geometry, and mechanical stress regulate the behavior of cortical microtubules at the subcellular and supercellular levels, giving rise to dramatic rearrangements in the cortical microtubule array in response to internal and external cues. Increasing evidence indicates that negative regulators of microtubules also contribute to the rearrangement of the cortical microtubule array. In this review, I summarize recent insights into how the rearrangement of the cortical microtubule array leads to proper, flexible cell wall patterning. PMID:25904930

  5. Carbapenem-resistant Klebsiella pneumoniae in high-risk haematological patients: factors favouring spread, risk factors and outcome of carbapenem-resistant Klebsiella pneumoniae bacteremias.

    PubMed

    Micozzi, Alessandra; Gentile, Giuseppe; Minotti, Clara; Cartoni, Claudio; Capria, Saveria; Ballarò, Daniele; Santilli, Stefania; Pacetti, Emanuele; Grammatico, Sara; Bucaneve, Giampaolo; Foà, Robin

    2017-03-10

    Carbapenem-resistant Klebsiella pneumoniae (CRKP) spread and infections in patients with haematological malignancies are a serious concern especially in endemic areas. Treatment failures and delay in appropriate therapy for CRKP infections are frequent and the mortality rate associated with CRKP bacteremia in neutropenic haematological patients is reported about 60%. Haematological patients harboring CRKP hospitalized between February 2012 and May 2013 in an Italian Teaching hospital were examined. Conditions favouring CRKP spread in a haematological unit, risk factors for bacteremia in CRKP-carriers and for CRKP bacteremia-related death were evaluated in this observational retrospective study. CRKP was isolated in 22 patients, 14 (64%) had bacteremia. Control measures implementation, particularly the weekly rectal screening for CRKP performed in all hospitalized patients and contact precautions for CRKP-carriers and newly admitted patients until proved CRKP-negative, reduced significantly the CRKP spread (14 new carriers identified of 131 screened patients vs 5 of 242 after the intervention, p = 0.001). Fifty-eight percent of carriers developed CRKP bacteremia, and acute myeloid leukemia (AML) resulted independently associated with the bacteremia occurrence (p = 0.02). CRKP bacteremias developed mainly during neutropenia (86%) and in CRKP-carriers (79%). CRKP bacteremias were breakthrough in 10 cases (71%). Ten of 14 patient with CRKP bacteremias died (71%) and all had AML. The 70% of fatal bacteremias occurred in patients not yet recognized as CRKP-carriers and 80% were breakthrough. Initial adequate antibiotic therapy resulted the only independent factor able to protect against death (p = 0.02). The identification of CRKP-carriers is confirmed critical to prevent CRKP spread. AML patients colonized by CRKP resulted at high risk of CRKP-bacteremia and poor outcome and the adequacy of the initial antibiotic therapy may be effective to improve survival

  6. Magnetic resonance imaging of trabecular and cortical bone in mice: comparison of high resolution in vivo and ex vivo MR images with corresponding histology.

    PubMed

    Weber, Michael H; Sharp, Jonathan C; Latta, Peter; Sramek, Milos; Hassard, H Thomas; Orr, F William

    2005-01-01

    Measurements of bone morphometry and remodeling have been shown to reflect bone strength and can be used to diagnose degenerative bone disease. In this study, in vivo and ex vivo magnetic resonance imaging (MRI) techniques to assess trabecular and cortical bone properties have been compared to each other and to histology as a novel means for the quantification of bone. Femurs of C57Bl/6 mice were examined both in vivo and ex vivo on an 11.7 T MRI scanner, followed by histologic processing and morphometry. A thresholding analysis technique was applied to the MRI images to generate contour lines and to delineate the boundaries between bone and marrow. Using MRI, an optimal correlation with histology was obtained with an in vivo longitudinal sectioned short echo time gradient-echo versus an in vivo long echo time spin-echo sequence or an ex vivo pulse sequence. Gradient-echo images were acquired with a maximum in-plane resolution of 35 microm. Our results demonstrated that in both the in vivo and ex vivo data sets, the percent area of marrow increases and percent area of trabecular bone and cortical bone thickness decreases moving from the epiphyseal growth plate to the diaphysis. These changes, observed with MRI, correlate with the histological data. Investigations using in vivo MRI gradient-echo sequences consistently gave the best correlation with histology. Our quantitative evaluation using both ex vivo and in vivo MRI was found to be an effective means to visualize non-invasively the normal variation in trabecular and cortical bone as compared to a histological "gold standard" The experiments validated in vivo MRI as a potential high resolution technique for investigating both soft tissue, such as marrow, and bone without radiation exposure.

  7. Ketamine Dysregulates the Amplitude and Connectivity of High-Frequency Oscillations in Cortical-Subcortical Networks in Humans: Evidence From Resting-State Magnetoencephalography-Recordings.

    PubMed

    Rivolta, Davide; Heidegger, Tonio; Scheller, Bertram; Sauer, Andreas; Schaum, Michael; Birkner, Katharina; Singer, Wolf; Wibral, Michael; Uhlhaas, Peter J

    2015-09-01

    Hypofunctioning of the N-methyl-D-aspartate receptor (NMDA-R) has been prominently implicated in the pathophysiology of schizophrenia (ScZ). The current study tested the effects of ketamine, a dissociative anesthetic and NMDA-R antagonist, on resting-state activity recorded with magnetoencephalography (MEG) in healthy volunteers. In a single-blind cross-over design, each participant (n = 12) received, on 2 different sessions, a subanesthetic dose of S-ketamine (0.006 mg/Kg) and saline injection. MEG-data were analyzed at sensor- and source-level in the beta (13-30 Hz) and gamma (30-90 Hz) frequency ranges. In addition, connectivity analysis at source-level was performed using transfer entropy (TE). Ketamine increased gamma-power while beta-band activity was decreased. Specifically, elevated 30-90 Hz activity was pronounced in subcortical (thalamus and hippocampus) and cortical (frontal and temporal cortex) regions, whilst reductions in beta-band power were localized to the precuneus, cerebellum, anterior cingulate, temporal and visual cortex. TE analysis demonstrated increased information transfer in a thalamo-cortical network after ketamine administration. The findings are consistent with the pronounced dysregulation of high-frequency oscillations following the inhibition of NMDA-R in animal models of ScZ as well as with evidence from electroencephalogram-data in ScZ-patients and increased functional connectivity during early illness stages. Moreover, our data highlight the potential contribution of thalamo-cortical connectivity patterns towards ketamine-induced neuronal dysregulation, which may be relevant for the understanding of ScZ as a disorder of disinhibition of neural circuits.

  8. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions

    DOE PAGES

    Zimmermann, Elizabeth A.; Schaible, Eric; Gludovatz, Bernd; ...

    2016-02-16

    Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality. Microarchitecture and mechanical properties of young, treatment-naïve osteoporosis, and bisphosphonate-treated cases were investigated in femoral cortices. Tissue strength was measured using three-point bending. Collagen fibril-level deformation was assessed in non-traumatic and traumatic fracture states using synchrotron small-angle x-ray scattering (SAXS) at low and high strain rates. The lower modulus, strength and fibrilmore » deformation measured at low strain rates reflects susceptibility for osteoporotic low-energy fragility fractures. Independent of age, disease and treatment status, SAXS revealed reduced fibril plasticity at high strain rates, characteristic of traumatic fracture. We find the significantly reduced mechanical integrity in osteoporosis may originate from porosity and alterations to the intra/extrafibrillar structure, while the fibril deformation under treatment indicates improved nano-scale characteristics. In conclusion, losses in strength and fibril deformation at low strain rates correlate with the occurrence of fragility fractures in osteoporosis, while improvements in structural and mechanical properties following bisphosphonate treatment may foster resistance to fracture during physiological strain rates.« less

  9. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions

    SciTech Connect

    Zimmermann, Elizabeth A.; Schaible, Eric; Gludovatz, Bernd; Schmidt, Felix N.; Riedel, Christoph; Krause, Matthias; Vettorazzi, Eik; Acevedo, Claire; Hahn, Michael; Püschel, Klaus; Tang, Simon; Amling, Michael; Ritchie, Robert O.; Busse, Björn

    2016-02-16

    Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality. Microarchitecture and mechanical properties of young, treatment-naïve osteoporosis, and bisphosphonate-treated cases were investigated in femoral cortices. Tissue strength was measured using three-point bending. Collagen fibril-level deformation was assessed in non-traumatic and traumatic fracture states using synchrotron small-angle x-ray scattering (SAXS) at low and high strain rates. The lower modulus, strength and fibril deformation measured at low strain rates reflects susceptibility for osteoporotic low-energy fragility fractures. Independent of age, disease and treatment status, SAXS revealed reduced fibril plasticity at high strain rates, characteristic of traumatic fracture. We find the significantly reduced mechanical integrity in osteoporosis may originate from porosity and alterations to the intra/extrafibrillar structure, while the fibril deformation under treatment indicates improved nano-scale characteristics. In conclusion, losses in strength and fibril deformation at low strain rates correlate with the occurrence of fragility fractures in osteoporosis, while improvements in structural and mechanical properties following bisphosphonate treatment may foster resistance to fracture during physiological strain rates.

  10. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions

    NASA Astrophysics Data System (ADS)

    Zimmermann, Elizabeth A.; Schaible, Eric; Gludovatz, Bernd; Schmidt, Felix N.; Riedel, Christoph; Krause, Matthias; Vettorazzi, Eik; Acevedo, Claire; Hahn, Michael; Püschel, Klaus; Tang, Simon; Amling, Michael; Ritchie, Robert O.; Busse, Björn

    2016-02-01

    Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality. Microarchitecture and mechanical properties of young, treatment-naïve osteoporosis, and bisphosphonate-treated cases were investigated in femoral cortices. Tissue strength was measured using three-point bending. Collagen fibril-level deformation was assessed in non-traumatic and traumatic fracture states using synchrotron small-angle x-ray scattering (SAXS) at low and high strain rates. The lower modulus, strength and fibril deformation measured at low strain rates reflects susceptibility for osteoporotic low-energy fragility fractures. Independent of age, disease and treatment status, SAXS revealed reduced fibril plasticity at high strain rates, characteristic of traumatic fracture. The significantly reduced mechanical integrity in osteoporosis may originate from porosity and alterations to the intra/extrafibrillar structure, while the fibril deformation under treatment indicates improved nano-scale characteristics. In conclusion, losses in strength and fibril deformation at low strain rates correlate with the occurrence of fragility fractures in osteoporosis, while improvements in structural and mechanical properties following bisphosphonate treatment may foster resistance to fracture during physiological strain rates.

  11. Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions

    PubMed Central

    Zimmermann, Elizabeth A.; Schaible, Eric; Gludovatz, Bernd; Schmidt, Felix N.; Riedel, Christoph; Krause, Matthias; Vettorazzi, Eik; Acevedo, Claire; Hahn, Michael; Püschel, Klaus; Tang, Simon; Amling, Michael; Ritchie, Robert O.; Busse, Björn

    2016-01-01

    Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality. Microarchitecture and mechanical properties of young, treatment-naïve osteoporosis, and bisphosphonate-treated cases were investigated in femoral cortices. Tissue strength was measured using three-point bending. Collagen fibril-level deformation was assessed in non-traumatic and traumatic fracture states using synchrotron small-angle x-ray scattering (SAXS) at low and high strain rates. The lower modulus, strength and fibril deformation measured at low strain rates reflects susceptibility for osteoporotic low-energy fragility fractures. Independent of age, disease and treatment status, SAXS revealed reduced fibril plasticity at high strain rates, characteristic of traumatic fracture. The significantly reduced mechanical integrity in osteoporosis may originate from porosity and alterations to the intra/extrafibrillar structure, while the fibril deformation under treatment indicates improved nano-scale characteristics. In conclusion, losses in strength and fibril deformation at low strain rates correlate with the occurrence of fragility fractures in osteoporosis, while improvements in structural and mechanical properties following bisphosphonate treatment may foster resistance to fracture during physiological strain rates. PMID:26879146

  12. Persistent patterns of interconnection in time-varying cortical networks estimated from high-resolution EEG recordings in humans during a simple motor act

    NASA Astrophysics Data System (ADS)

    DeVico Fallani, F.; Latora, V.; Astolfi, L.; Cincotti, F.; Mattia, D.; Marciani, M. G.; Salinari, S.; Colosimo, A.; Babiloni, F.

    2008-06-01

    In this work, a novel approach based on the estimate of time-varying graph indices is proposed in order to capture the basic schemes of communication within the functional brain networks during a simple motor act. To achieve this, we used a cascade of computational tools able to estimate first the electrical activity of the cortical surface by using high-resolution EEG techniques. From the cortical signals of different regions of interests we estimated the time-varying functional connectivity patterns by means of the adaptive partial directed coherence. The time-varying connectivity estimation returns a series of networks evolving during the examined task which can be summarized and interpreted with the aid of mathematical indices based on graph theory. The combination of all these methods is demonstrated on a set of high-resolution EEG data recorded from a group of healthy subjects performing a simple foot movement. It can be anticipated that the combination of the time-varying connectivity with the theoretical graph analysis is able to reveal precious information about the interconnections of the cerebral network as the significant persistence of mutual links and three-node motifs.

  13. Effects of high-dose gamma irradiation on tensile properties of human cortical bone: Comparison of different radioprotective treatment methods.

    PubMed

    Allaveisi, Farzaneh; Mirzaei, Majid

    2016-08-01

    There are growing interests in the radioprotective methods that can reduce the damaging effects of ionizing radiation on sterilized bone allografts. The aim of this study was to investigate the effects of 50kGy (single dose, and fractionated) gamma irradiation, in presence and absence of l-Cysteine (LC) free radical scavenger, on tensile properties of human femoral cortical bone. A total of 48 standard tensile test specimens was prepared from diaphysis of femurs of three male cadavers (age: 52, 52, and 54 years). The specimens were assigned to six groups (n=8) according to different irradiation schemes, i.e.; Control (Non-irradiated), LC-treated control, a single dose of 50kGy (sole irradiation), a single dose of 50kGy in presence of LC, 10 fractions of 5kGy (sole irradiation), and 10 fractions of 5kGy in presence of LC. Uniaxial tensile tests were carried out to evaluate the variations in tensile properties of the specimens. Fractographic analysis was performed to examine the microstructural features of the fracture surfaces. The results of multivariate analysis showed that fractionation of the radiation dose, as well as the LC treatment of the 50kGy irradiated specimens, significantly reduced the radiation-induced impairment of the tensile properties of the specimens (P<0.05). The fractographic observations were consistent with the mechanical test results. In summary, this study showed that the detrimental effects of gamma sterilization on tensile properties of human cortical bone can be substantially reduced by free radical scavenger treatment, dose fractionation, and the combined treatment of these two methods. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Dual Cortical Plasticity After Spinal Cord Injury.

    PubMed

    Humanes-Valera, Desire; Foffani, Guglielmo; Alonso-Calviño, Elena; Fernández-López, Elena; Aguilar, Juan

    2017-05-01

    During cortical development, plasticity reflects the dynamic equilibrium between increasing and decreasing functional connectivity subserved by synaptic sprouting and pruning. After adult cortical deafferentation, plasticity seems to be dominated by increased functional connectivity, leading to the classical expansive reorganization from the intact to the deafferented cortex. In contrast, here we show a striking "decrease" in the fast cortical responses to high-intensity forepaw stimulation 1-3 months after complete thoracic spinal cord transection, as evident in both local field potentials and intracellular in vivo recordings. Importantly, this decrease in fast cortical responses co-exists with an "increase" in cortical activation over slower post-stimulus timescales, as measured by an increased forepaw-to-hindpaw propagation of stimulus-triggered cortical up-states, as well as by the enhanced slow sustained depolarization evoked by high-frequency forepaw stimuli in the deafferented hindpaw cortex. This coincidence of diminished fast cortical responses and enhanced slow cortical activation offers a dual perspective of adult cortical plasticity after spinal cord injury. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Auditory processing in schizophrenia during the middle latency period (10–50 ms): high-density electrical mapping and source analysis reveal subcortical antecedents to early cortical deficits

    PubMed Central

    Leavitt, Victoria M.; Molholm, Sophie; Ritter, Walter; Shpaner, Marina; Foxe, John J.

    2007-01-01

    Introduction Auditory sensory processing dysfunction is a core component of schizophrenia, with deficits occurring at 50 ms post-stimulus firmly established in the literature. Given that the initial afference of primary auditory cortex occurs at least 35 ms earlier, however, an essential question remains: how early in sensory processing do such deficits arise, and do they occur during initial cortical afference or earlier, which would implicate subcortical auditory dysfunction. Objective To establish the onset of the earliest deficits in auditory processing, we examined the time window demarcating the transition from subcortical to cortical processing: 10 ms to 50 ms during the so-called middle latency responses (MLRs). These remain to be adequately characterized in patients with schizophrenia. Methods We recorded auditory evoked potentials (AEPs) to simple tone-pips from 15 control subjects and 21 medicated patients with longer-term schizophrenia or schizoaffective disorder (illness duration 16 yr, standard deviation [SD] 9.4 yr), using high-density electrical scalp recordings. Between-group analyses assessed the integrity of the MLRs across groups. In addition, 2 source-localization models were conducted to address whether a distinction between subcortical and cortical generators of the MLRs can be made and whether evidence for differential dorsal and ventral pathway contributions to auditory processing deficits can be established. Results Robust auditory processing deficits were found for patients as early as 15 ms. Evidence for subcortical generators of the earliest MLR component (P20) was provided by source analysis. Topographical mapping and source localization also pointed to greater decrements in processing in the dorsal auditory pathway of patients, providing support for a theory of pervasive deficits that are organized along the lines of a dorsal–ventral distinction. Conclusions Auditory sensory dysfunction in schizophrenia begins extremely early in

  16. Renal cortical retention of contrast medium on delayed CT and nephropathy following transcatheter arterial chemoembolisation in patients with high serum creatinine level.

    PubMed

    Yamazaki, H; Oi, H; Matshushita, M; Inoue, T; Nakamura, H; Inoue, T

    2002-11-01

    The aim of this study was to investigate the prevalence of renal cortical retention (RCR) of contrast media seen on delayed CT, and nephropathy following transarterial chemoembolisation (TACE) in high-risk patients. The findings of 18 patients with abnormally high serum creatinine levels who underwent TACE were reviewed. Nephropathy was defined as an increase in serum creatinine level of more than 44 micromol l(-1), or more than 25%, on day 1, 3, 7 or 14. RCR was defined as mild (CT value >50) or severe (CT value >100). RCR was seen in 16 cases (89%) and in seven cases (39%) of post-TACE nephropathy. Patients without severe RCR did not develop nephropathy post-TACE, whereas 50% of those with such retention did (p=0.19). Delayed CT appears to have the potential as an early detector of nephropathy post-TACE in high-risk patients.

  17. Test-retest variability of high resolution positron emission tomography (PET) imaging of cortical serotonin (5HT2A) receptors in older, healthy adults

    PubMed Central

    2009-01-01

    Background Position emission tomography (PET) imaging using [18F]-setoperone to quantify cortical 5-HT2A receptors has the potential to inform pharmacological treatments for geriatric depression and dementia. Prior reports indicate a significant normal aging effect on serotonin 5HT2A receptor (5HT2AR) binding potential. The purpose of this study was to assess the test-retest variability of [18F]-setoperone PET with a high resolution scanner (HRRT) for measuring 5HT2AR availability in subjects greater than 60 years old. Methods: Six healthy subjects (age range = 65–78 years) completed two [18F]-setoperone PET scans on two separate occasions 5–16 weeks apart. Results The average difference in the binding potential (BPND) as measured on the two occasions in the frontal and temporal cortical regions ranged between 2 and 12%, with the lowest intraclass correlation coefficient in anterior cingulate regions. Conclusion We conclude that the test-retest variability of [18F]-setoperone PET in elderly subjects is comparable to that of [18F]-setoperone and other 5HT2AR radiotracers in younger subject samples. PMID:19580676

  18. High-frequency stimulation of the subthalamic nucleus counteracts cortical expression of major histocompatibility complex genes in a rat model of Parkinson's disease.

    PubMed

    Grieb, Benjamin; Engler, Gerhard; Sharott, Andrew; von Nicolai, Constantin; Streichert, Thomas; Papageorgiou, Ismini; Schulte, Alexander; Westphal, Manfred; Lamszus, Katrin; Engel, Andreas K; Moll, Christian K E; Hamel, Wolfgang

    2014-01-01

    High-frequency stimulation of the subthalamic nucleus (STN-HFS) is widely used as therapeutic intervention in patients suffering from advanced Parkinson's disease. STN-HFS exerts a powerful modulatory effect on cortical motor control by orthodromic modulation of basal ganglia outflow and via antidromic activation of corticofugal fibers. However, STN-HFS-induced changes of the sensorimotor cortex are hitherto unexplored. To address this question at a genomic level, we performed mRNA expression analyses using Affymetrix microarray gene chips and real-time RT-PCR in sensorimotor cortex of parkinsonian and control rats following STN-HFS. Experimental parkinsonism was induced in Brown Norway rats by bilateral nigral injections of 6-hydroxydopamine and was assessed histologically, behaviorally, and electrophysiologically. We applied prolonged (23h) unilateral STN-HFS in awake and freely moving animals, with the non-stimulated hemisphere serving as an internal control for gene expression analyses. Gene enrichment analysis revealed strongest regulation in major histocompatibility complex (MHC) related genes. STN-HFS led to a cortical downregulation of several MHC class II (RT1-Da, Db1, Ba, and Cd74) and MHC class I (RT1CE) encoding genes. The same set of genes showed increased expression levels in a comparison addressing the effect of 6-hydroxydopamine lesioning. Hence, our data suggest the possible association of altered microglial activity and synaptic transmission by STN-HFS within the sensorimotor cortex of 6-hydroxydopamine treated rats.

  19. A Comparison of the Spread of the Folk High School Idea in Denmark, Finland, Norway, Sweden, and the United States.

    ERIC Educational Resources Information Center

    Larson, Dean Gordon

    Comparing folk high schools in the United States and Scandinavia, this study investigated the philosophical and historical development of the movement, the relationship of folk high schools to other institutions in each nation studied, and conditions which have contributed to successful implementation of the idea. Data came from a literature…

  20. A Comparison of the Spread of the Folk High School Idea in Denmark, Finland, Norway, Sweden, and the United States.

    ERIC Educational Resources Information Center

    Larson, Dean Gordon

    Comparing folk high schools in the United States and Scandinavia, this study investigated the philosophical and historical development of the movement, the relationship of folk high schools to other institutions in each nation studied, and conditions which have contributed to successful implementation of the idea. Data came from a literature…

  1. Correlates of spreading depolarization in human scalp electroencephalography

    PubMed Central

    Drenckhahn, Christoph; Winkler, Maren K. L.; Major, Sebastian; Scheel, Michael; Kang, Eun-Jeung; Pinczolits, Alexandra; Grozea, Cristian; Hartings, Jed A.; Woitzik, Johannes

    2012-01-01

    It has been known for decades that suppression of spontaneous scalp electroencephalographic activity occurs during ischaemia. Trend analysis for such suppression was found useful for intraoperative monitoring during carotid endarterectomy, or as a screening tool to detect delayed cerebral ischaemia after aneurismal subarachnoid haemorrhage. Nevertheless, pathogenesis of such suppression of activity has remained unclear. In five patients with aneurismal subarachnoid haemorrhage and four patients with decompressive hemicraniectomy after malignant hemispheric stroke due to middle cerebral artery occlusion, we here performed simultaneously full-band direct and alternating current electroencephalography at the scalp and direct and alternating current electrocorticography at the cortical surface. After subarachnoid haemorrhage, 275 slow potential changes, identifying spreading depolarizations, were recorded electrocorticographically over 694 h. Visual inspection of time-compressed scalp electroencephalography identified 193 (70.2%) slow potential changes [amplitude: −272 (−174, −375) µV (median quartiles), duration: 5.4 (4.0, 7.1) min, electrocorticography–electroencephalography delay: 1.8 (0.8, 3.5) min]. Intervals between successive spreading depolarizations were significantly shorter for depolarizations with electroencephalographically identified slow potential change [33.0 (27.0, 76.5) versus 53.0 (28.0, 130.5) min, P = 0.009]. Electroencephalography was thus more likely to display slow potential changes of clustered than isolated spreading depolarizations. In contrast to electrocorticography, no spread of electroencephalographic slow potential changes was seen, presumably due to superposition of volume-conducted electroencephalographic signals from widespread cortical generators. In two of five patients with subarachnoid haemorrhage, serial magnetic resonance imaging revealed large delayed infarcts at the recording site, while electrocorticography

  2. Analysis of plant sterol and stanol esters in cholesterol-lowering spreads and beverages using high-performance liquid chromatography-atmospheric pressure chemical ionization-mass spectroscopy.

    PubMed

    Mezine, Igor; Zhang, Huizhen; Macku, Carlos; Lijana, Robert

    2003-09-10

    Plant sterol and stanol esters were separated on a Luna hexyl-phenyl column using a gradient of acetonitrile (90-100%) in water. The eluted compounds were detected by atmospheric pressure chemical ionization (APCI)-mass spectroscopy (MS) in the positive mode. Sterol and stanol esters produced [M + H - HOOCR](+) ions. Application of the hyphenated technique-LC-MS-allowed differentiation between a number of esters of sitosterol, campesterol, stigmasterol, and (tentatively) avenasterol, as well as sitostanol and campestanol esters. With cholesteryl decanoate used as the internal standard, the method showed good linearity, precision, and reproducibility. The method required minimal sample pretreatment and can be applied to samples with high water content (juices) as well as samples with high oil content (margarine spreads). The method could be useful for the analysis of sterol and stanol esters in fortified food products.

  3. Functional brain network organisation of children between 2 and 5 years derived from reconstructed activity of cortical sources of high-density EEG recordings.

    PubMed

    Bathelt, Joe; O'Reilly, Helen; Clayden, Jonathan D; Cross, J Helen; de Haan, Michelle

    2013-11-15

    There is increasing interest in applying connectivity analysis to brain measures (Rubinov and Sporns, 2010), but most studies have relied on fMRI, which substantially limits the participant groups and numbers that can be studied. High-density EEG recordings offer a comparatively inexpensive easy-to-use alternative, but require channel-level connectivity analysis which currently lacks a common analytic framework and is very limited in spatial resolution. To address this problem, we have developed a new technique for studies of network development that overcomes the spatial constraint and obtains functional networks of cortical areas by using EEG source reconstruction with age-matched average MRI templates (He et al., 1999). In contrast to previously reported channel-level analysis, this approach provides information about the cortical areas most likely to be involved in the network as well as their functional relationship (Babiloni et al., 2005; De Vico Fallani et al., 2007). In this study, we applied source reconstruction with age-matched templates to task-free high-density EEG recordings in typically-developing children between 2 and 6 years of age (O'Reilly, 2012). Graph theory was then applied to the association strengths of 68 cortical regions of interest based on the Desikan-Killiany atlas. We found linear increases of mean node degree, mean clustering coefficient and maximum betweenness centrality between 2 years and 6 years of age. Characteristic path length was negatively correlated with age. The correlation of the network measures with age indicates network development towards more closely integrated networks similar to reports from other imaging modalities (Fair et al., 2008; Power et al., 2010). We also applied eigenvalue decomposition to obtain functional modules (Clayden et al., 2013). Connection strength within these modules did not change with age, and the modules resembled hub networks previously described for MRI (Hagmann et al., 2010; Power et al

  4. Differential recruitment of high frequency wavelets (600 Hz) and primary cortical response (N20) in human median nerve somatosensory evoked potentials.

    PubMed

    Klostermann, F; Nolte, G; Losch, F; Curio, G

    1998-11-06

    Human median nerve somatosensory evoked potentials contain a burst of high-frequency (600 Hz) wavelets superimposed on the primary cortical response (N20). These presumably reflect highly-synchronized repetitive thalamic and/or intracortical population spike bursts and are diminished in non-REM sleep with N20 persisting. Here the burst/N20 relation in awake subjects was examined by using eight different intensities of electric median nerve stimuli. In all subjects the amplitude recruitment of both N20 and burst could be modeled adequately as a sigmoidal function of stimulus intensity. While 8/10 subjects showed a parallel recruitment, 2/10 subjects required significantly higher stimulation intensities for burst than for N20 recruitment. This dampened burst recruitment possibly reflects slight vigilance fluctuations in open-eyed awake subjects; a further increase of burst thresholds could explain the burst attenuation when entering shallow sleep.

  5. Cortical transients preceding voluntary movement.

    PubMed

    Hartwell, J W

    2009-12-01

    The process of initiating a voluntary muscular movement evidently involves a focusing of diffuse brain activity onto a highly specific location in the primary motor cortex. Even the very simple stereotypic movements used to study the 'contingent negative variation' and the 'readiness potential' begin with EEG indicative of widely distributed brain activity. In natural settings the involvement of diffuse cortical networks is undoubtedly even more important. Eventually, however, activity must coalesce onto specific neurons for the intended movement to ensue. Here we examine that focusing process from a mathematical point of view. Using a digital simulation, we solve the global equations for cortical dynamics and model the flow from diffuse onset to localized spike. From this perspective the interplay between global and local effects is seen as a necessary consequence of a basic cortical architecture which supports wave propagation. Watching the process evolve over time allows us to estimate some characteristic amplitudes and delays.

  6. High frequency green function for aerodynamic noise in moving media. I - General theory. II - Noise from a spreading jet

    NASA Technical Reports Server (NTRS)

    Durbin, P. A.

    1983-01-01

    It is shown how a high frequency analysis can be made for general problems involving flow-generated noise. In the parallel shear flow problem treated by Balsa (1976) and Goldstein (1982), the equation governing sound propagation in the moving medium could be transformed into a wave equation for a stationary medium with an inhomogeneous index of refraction. It is noted that the procedure of Avila and Keller (1963) was then used to construct a high frequency Green function. This procedure involves matching a solution valid in an inner region around the point source to an outer, ray-acoustics solution. This same procedure is used here to construct the Green function for a source in an arbitrary mean flow. In view of the fact that there is no restriction to parallel flow, the governing equations cannot be transformed into a wave equation; the analysis therefore proceeds from the equations of motion themselves.

  7. Evolution, global spread, and pathogenicity of highly pathogenic avian influenza H5Nx clade 2.3.4.4

    USDA-ARS?s Scientific Manuscript database

    Novel subtypes of Eurasian-origin (Goose/Guangdong lineage) H5 highly pathogenic avian influenza (HPAI) viruses belonging to clade 2.3.4 such as H5N2, H5N5, H5N6, and H5N8 have been identified in China since 2008 and subsequently evolved into four genetically distinct groups (A – D) of clade 2.3.4.4...

  8. The Internet Alert Project: spreading the word about high-risk sexual activities advertised on the Internet.

    PubMed

    Kachur, R E

    2004-11-01

    The Internet is an emerging venue for facilitating high-risk sexual behavior; in particular, use of the Internet to seek out sex partners has been shown to be associated with high-risk sexual behaviors, such as an increase in number of sexual partners and an increase in anal sex, which can increase the risk of contracting and transmitting sexually transmitted diseases (STDs) including HIV. In an effort to assist health departments around the country, the Internet Alert Project was developed to provide Centers for Disease Control and Prevention (CDC) project officers and field staff with information about Internet-advertised, high-risk sexual activities in areas that do not have access to sexually explicit material on the Internet. An evaluation was conducted to determine the utility of the Internet Alert Project, its effect on knowledge and awareness of recipients and on public health efforts. Results of the evaluation show the alerts are a useful and valuable tool. The alerts have helped to increase knowledge about sexually-related uses of the Internet and have also driven public health efforts in the field. The results also indicate the need for project areas to access information found on the Internet in order to keep up with the ever-changing behaviors of at-risk populations.

  9. Raman spectral markers of collagen denaturation and hydration in human cortical bone tissue are affected by radiation sterilization and high cycle fatigue damage.

    PubMed

    Flanagan, Christopher D; Unal, Mustafa; Akkus, Ozan; Rimnac, Clare M

    2017-11-01

    Thermal denaturation and monotonic mechanical damage alter the organic and water-related compartments of cortical bone. These changes can be detected using Raman spectroscopy. However, less is known regarding Raman sensitivity to detect the effects of cyclic fatigue damage and allograft sterilization doses of gamma radiation. To determine if Raman spectroscopic biomarkers of collagen denaturation and hydration are sensitive to the effects of (a) high cycle fatigue damage and (b) 25kGy irradiation. Unirradiated and gamma-radiation sterilized human cortical bone specimens previously tested in vitro under high-cycle (> 100,000 cycles) fatigue conditions at 15MPa, 25MPa, 35MPa, 45MPa, and 55MPa cyclic stress levels were studied. Cortical bone Raman spectral profiles from wavenumber ranges of 800-1750cm(-1) and 2700-3800cm(-1) were obtained and compared from: a) non-fatigue vs fatigue fracture sites and b) radiated vs. unirradiated states. Raman biomarker ratios 1670/1640 and 3220/2949, which reflect collagen denaturation and organic matrix (mainly collagen)-bound water, respectively, were assessed. One- and two-way ANOVA analyses were utilized to identify differences between groups along with interaction effects between cyclic fatigue and radiation-induced damage. Cyclic fatigue damage resulted in increases in collagen denaturation (1670/1640: 1.517 ± 0.043 vs 1.579 ± 0.021, p < 0.001) and organic matrix-bound water (3220/2949: 0.109 ± 0.012 vs 0.131 ± 0.008, p < 0.001). Organic matrix-bound water increased secondary to 25kGy irradiation (3220/2949: 0.105 ± 0.010 vs 0.1161 ± 0.009, p = 0.003). Organic matrix-bound water was correlated positively with collagen denaturation (r = 0.514, p < 0.001). Raman spectroscopy can detect the effects of cyclic fatigue damage and 25kGy irradiation via increases in organic matrix (mainly collagen)-bound water. A Raman measure of collagen denaturation was sensitive to cyclic fatigue damage but not 25kGy irradiation. Collagen

  10. Creutzfeldt-Jakob Disease with a prion protein gene codon 180 mutation presenting asymmetric cortical high-intensity on magnetic resonance imaging.

    PubMed

    Amano, Yuko; Kimura, Noriyuki; Hanaoka, Takuya; Aso, Yasuhiro; Hirano, Teruyuki; Murai, Hiroyuki; Satoh, Katsuya; Matsubara, Etsuro

    2015-01-01

    Here we report a genetically confirmed case of Creutzfeldt-Jakob disease with a prion protein gene codon 180 mutation presenting atypical magnetic resonance imaging findings. The present case exhibited an acute onset and lateralized neurologic signs, and progressive cognitive impairment. No myoclonus or periodic synchronous discharges on electroencephalography were observed. Diffusion-weighted images revealed areas of high signal intensity in the right frontal and temporal cortices at onset that extended to the whole cortex and basal ganglia of the right cerebral hemisphere at 3 months. Although the cerebrospinal fluid (CSF) was initially negative for neuron specific enolase, tau protein, 14-3-3 protein, and abnormal prion protein, the CSF was positive for these brain-derived proteins at 3 months after onset.

  11. New Introductions, Spread of Existing Matrilines, and High Rates of Pyrethroid Resistance Result in Chronic Infestations of Bed Bugs (Cimex lectularius L.) in Lower-Income Housing

    PubMed Central

    Raab, Ronald W.; Moore, Julia E.; Vargo, Edward L.; Rose, Lucy; Raab, Julie; Culbreth, Madeline; Burzumato, Gracie; Koyee, Aurvan; McCarthy, Brittany; Raffaele, Jennifer; Schal, Coby; Vaidyanathan, Rajeev

    2016-01-01

    Infestations of the common bed bug (Cimex lectularius L.) have increased substantially in the United States in the past 10–15 years. The housing authority in Harrisonburg, Virginia, conducts heat-treatments after bed bugs are detected in a lower-income housing complex, by treating each infested unit at 60°C for 4–6 hours. However, a high frequency of recurrent infestations called into question the efficacy of this strategy. Genetic analysis using Bayesian clustering of polymorphic microsatellite loci from 123 bed bugs collected from 23 units from May 2012 to April 2013 in one building indicated that (a) 16/21 (73%) infestations were genetically similar, suggesting ineffective heat-treatments or reintroductions from within the building or from a common external source, followed by local spread of existing populations; and (b) up to 5 of the infestations represented new genotypes, indicating that 5 new populations were introduced into this building in one year, assuming they were not missed in earlier screens. There was little to no gene flow among the 8 genetic clusters identified in the building. Bed bugs in the U.S. often possess one or both point mutations in the voltage-gated sodium channel, termed knockdown resistance (kdr), from valine to leucine (V419L) and leucine to isoleucine (L925I) that confer target-site resistance against pyrethroid insecticides. We found that 48/121 (40%) bed bugs were homozygous for both kdr mutations (L419/I925), and a further 59% possessed at least one of the kdr mutations. We conclude that ineffective heat treatments, new introductions, reintroductions and local spread, and an exceptionally high frequency of pyrethroid resistance are responsible for chronic infestations in lower-income housing. Because heat treatments fail to protect from reintroductions, and pesticide use has not decreased the frequency of infestations, preventing new introductions and early detection are the most effective strategies to avoid bed bug

  12. New Introductions, Spread of Existing Matrilines, and High Rates of Pyrethroid Resistance Result in Chronic Infestations of Bed Bugs (Cimex lectularius L.) in Lower-Income Housing.

    PubMed

    Raab, Ronald W; Moore, Julia E; Vargo, Edward L; Rose, Lucy; Raab, Julie; Culbreth, Madeline; Burzumato, Gracie; Koyee, Aurvan; McCarthy, Brittany; Raffaele, Jennifer; Schal, Coby; Vaidyanathan, Rajeev

    2016-01-01

    Infestations of the common bed bug (Cimex lectularius L.) have increased substantially in the United States in the past 10-15 years. The housing authority in Harrisonburg, Virginia, conducts heat-treatments after bed bugs are detected in a lower-income housing complex, by treating each infested unit at 60°C for 4-6 hours. However, a high frequency of recurrent infestations called into question the efficacy of this strategy. Genetic analysis using Bayesian clustering of polymorphic microsatellite loci from 123 bed bugs collected from 23 units from May 2012 to April 2013 in one building indicated that (a) 16/21 (73%) infestations were genetically similar, suggesting ineffective heat-treatments or reintroductions from within the building or from a common external source, followed by local spread of existing populations; and (b) up to 5 of the infestations represented new genotypes, indicating that 5 new populations were introduced into this building in one year, assuming they were not missed in earlier screens. There was little to no gene flow among the 8 genetic clusters identified in the building. Bed bugs in the U.S. often possess one or both point mutations in the voltage-gated sodium channel, termed knockdown resistance (kdr), from valine to leucine (V419L) and leucine to isoleucine (L925I) that confer target-site resistance against pyrethroid insecticides. We found that 48/121 (40%) bed bugs were homozygous for both kdr mutations (L419/I925), and a further 59% possessed at least one of the kdr mutations. We conclude that ineffective heat treatments, new introductions, reintroductions and local spread, and an exceptionally high frequency of pyrethroid resistance are responsible for chronic infestations in lower-income housing. Because heat treatments fail to protect from reintroductions, and pesticide use has not decreased the frequency of infestations, preventing new introductions and early detection are the most effective strategies to avoid bed bug

  13. Oman diopsidites: a new lithology diagnostic of very high temperature hydrothermal circulation in mantle peridotite below oceanic spreading centres

    NASA Astrophysics Data System (ADS)

    Python, Marie; Ceuleneer, Georges; Ishida, Yoshito; Barrat, Jean-Alix; Arai, Shoji

    2007-03-01

    Mafic-ultramafic dykes scattered in the mantle section of ophiolites are generally crystallisation products from common silicate melts. In the frame of a global survey of these melt migration relics in the Oman mantle harzburgites, we discovered a peculiar lithology made essentially of pure diopside ( 0.95<{Mg}/{Mg+Fe}<1) whose characteristics do not match a magmatic or mantle origin. Arguments against a magmatic or mantle origin for these diopsidites combine compositional and textural evidence. In spite of their refractory composition, they are strongly depleted in Cr (Cr 2O 3 0.2 wt.%). By the same way other minor elements (Al, Ti, Na…) and rare earth elements have peculiarly low abundances and plot away from magmatic differentiation trends. In a few samples, the paragenetic association includes pure anorthite (An% up to 0.99), minor amounts of forsterite (Fo > 0.95) or traces of andradite. When not deformed, the diopsides are automorphic and their texture points to metamorphic growth in a matrix composed of antigorite and/or carbonate. Diopsidites have textures reminiscent to that of skarns developing in contact metamorphic halos or that of rodingite frequently present in the serpentine bodies of the ophiolitic crust. They frequently appear as dykes (former cracks), with a few mm to few tens of cm wide transitional zones, which contain high amounts of hydrous minerals, between the diopsidite facies and its host rock. The diopsidites are not randomly distributed in the Oman ophiolite, being more abundant near former asthenospheric diapirs emplaced at shallow depth in the lithosphere. We interpret the diopsidites as the footprint of very high temperature circulation of seawater and carbonated fluids (> 800 °C), which may have leached plagioclase rich lithologies before penetrating the mantle (as shown by a well developed positive Eu anomaly). Our data confirm the prediction of McCollom and Shock [T.M. McCollom, E.L. Shock, Fluid-rock interactions in the lower

  14. Learning to Characterize Submarine Lava Flow Morphology at Seamounts and Spreading Centers using High Definition Video and Photomosaics

    NASA Astrophysics Data System (ADS)

    Fundis, A. T.; Sautter, L. R.; Kelley, D. S.; Delaney, J. R.; Kerr-Riess, M.; Denny, A. R.; Elend, M.

    2010-12-01

    In August, 2010 the UW ENLIGHTEN ’10 expedition provided ~140 hours of seafloor HD video footage at Axial Seamount, the most magmatically robust submarine volcano on the Juan de Fuca Ridge. During this expedition, direct imagery from an Insite Pacific HD camera mounted on the ROV Jason 2 was used to classify broad expanses of seafloor where high power (8 kw) and high bandwidth (10 Gb/s) fiber optic cable will be laid as part of the Regional Scale Nodes (RSN) component of the NSF funded Ocean Observatories Initiative. The cable will provide power and two-way, real-time communication to an array of >20 sensors deployed at the summit of the volcano and at active sites of hydrothermal venting to investigate how active processes within the volcano and at seafloor hot springs within the caldera are connected. In addition to HD imagery, over 10,000 overlapping photographs from a down-looking still camera were merged and co-registered to create high resolution photomosaics of two areas within Axial’s caldera. Thousands of additional images were taken to characterize the seafloor along proposed cable routes, allowing optimal routes to be planned well in advance of deployment. Lowest risk areas included those free of large collapse basins, steep flow fronts and fissures. Characterizing the modes of lava distribution across the seafloor is crucial to understanding the construction history of the upper oceanic crust at mid-ocean ridges. In part, reconstruction of crustal development and eruptive histories can be inferred from surface flow morphologies, which provide insights into lava emplacement dynamics and effusion rates of past eruptions. An online resource is under development that will educate students about lava flow morphologies through the use of HD video and still photographs. The objective of the LavaFlow exercise is to map out a proposed cable route across the Axial Seamount caldera. Students are first trained in appropriate terminology and background content

  15. Cortical Depth Dependence of the Diffusion Anisotropy in the Human Cortical Gray Matter In Vivo

    PubMed Central

    Truong, Trong-Kha; Guidon, Arnaud; Song, Allen W.

    2014-01-01

    Diffusion tensor imaging (DTI) is typically used to study white matter fiber pathways, but may also be valuable to assess the microstructure of cortical gray matter. Although cortical diffusion anisotropy has previously been observed in vivo, its cortical depth dependence has mostly been examined in high-resolution ex vivo studies. This study thus aims to investigate the cortical depth dependence of the diffusion anisotropy in the human cortex in vivo on a clinical 3 T scanner. Specifically, a novel multishot constant-density spiral DTI technique with inherent correction of motion-induced phase errors was used to achieve a high spatial resolution (0.625×0.625×3 mm) and high spatial fidelity with no scan time penalty. The results show: (i) a diffusion anisotropy in the cortical gray matter, with a primarily radial diffusion orientation, as observed in previous ex vivo and in vivo studies, and (ii) a cortical depth dependence of the fractional anisotropy, with consistently higher values in the middle cortical lamina than in the deep and superficial cortical laminae, as observed in previous ex vivo studies. These results, which are consistent across subjects, demonstrate the feasibility of this technique for investigating the cortical depth dependence of the diffusion anisotropy in the human cortex in vivo. PMID:24608869

  16. Cortical depth dependence of the diffusion anisotropy in the human cortical gray matter in vivo.

    PubMed

    Truong, Trong-Kha; Guidon, Arnaud; Song, Allen W

    2014-01-01

    Diffusion tensor imaging (DTI) is typically used to study white matter fiber pathways, but may also be valuable to assess the microstructure of cortical gray matter. Although cortical diffusion anisotropy has previously been observed in vivo, its cortical depth dependence has mostly been examined in high-resolution ex vivo studies. This study thus aims to investigate the cortical depth dependence of the diffusion anisotropy in the human cortex in vivo on a clinical 3 T scanner. Specifically, a novel multishot constant-density spiral DTI technique with inherent correction of motion-induced phase errors was used to achieve a high spatial resolution (0.625 × 0.625 × 3 mm) and high spatial fidelity with no scan time penalty. The results show: (i) a diffusion anisotropy in the cortical gray matter, with a primarily radial diffusion orientation, as observed in previous ex vivo and in vivo studies, and (ii) a cortical depth dependence of the fractional anisotropy, with consistently higher values in the middle cortical lamina than in the deep and superficial cortical laminae, as observed in previous ex vivo studies. These results, which are consistent across subjects, demonstrate the feasibility of this technique for investigating the cortical depth dependence of the diffusion anisotropy in the human cortex in vivo.

  17. 3D assessment of cortical bone porosity and tissue mineral density using high-resolution µCT: effects of resolution and threshold method.

    PubMed

    Palacio-Mancheno, Paolo E; Larriera, Adriana I; Doty, Stephen B; Cardoso, Luis; Fritton, Susannah P

    2014-01-01

    Current micro-computed tomography (µCT) systems allow scanning bone at resolutions capable of three-dimensional (3D) characterization of intracortical vascular porosity and osteocyte lacunae. However, the scanning and reconstruction parameters along with the image segmentation method affect the accuracy of the measurements. In this study, the effects of scanning resolution and image threshold method in quantifying small features of cortical bone (vascular porosity, vascular canal diameter and separation, lacunar porosity and density, and tissue mineral density) were analyzed. Cortical bone from the tibia of Sprague-Dawley rats was scanned at 1-µm and 4-µm resolution, reconstructions were density-calibrated, and volumes of interest were segmented using approaches based on edge-detection or histogram analysis. In 1-µm resolution scans, the osteocyte lacunar spaces could be visualized, and it was possible to separate the lacunar porosity from the vascular porosity. At 4-µm resolution, the vascular porosity and vascular canal diameter were underestimated, and osteocyte lacunae were not effectively detected, whereas the vascular canal separation and tissue mineral density were overestimated compared to 1-µm resolution. Resolution had a much greater effect on the measurements than did threshold method, showing partial volume effects at resolutions coarser than 2 µm in two separate analyses, one of which assessed the effect of resolution on an object of known size with similar architecture to a vascular pore. Although there was little difference when using the edge-detection versus histogram-based threshold approaches, edge-detection was somewhat more effective in delineating canal architecture at finer resolutions (1-2 µm). In addition, use of a high-resolution (1 µm) density-based threshold on lower resolution (4 µm) density-calibrated images was not effective in improving the lower-resolution measurements. In conclusion, if measuring cortical vascular

  18. 3D Assessment of Cortical Bone Porosity and Tissue Mineral Density Using High-Resolution Micro-CT: Effects of Resolution and Threshold Method

    PubMed Central

    Palacio-Mancheno, Paolo E.; Larriera, Adriana I.; Doty, Stephen B.; Cardoso, Luis; Fritton, Susannah P.

    2013-01-01

    Current micro-CT systems allow scanning bone at resolutions capable of three-dimensional characterization of intracortical vascular porosity and osteocyte lacunae. However, the scanning and reconstruction parameters along with the image segmentation method affect the accuracy of the measurements. In this study, the effects of scanning resolution and image threshold method in quantifying small features of cortical bone (vascular porosity, vascular canal diameter and separation, lacunar porosity and density, and tissue mineral density) were analyzed. Cortical bone from the tibia of Sprague-Dawley rats was scanned at 1-µm and 4-µm resolutions, reconstructions were density-calibrated, and volumes of interest were segmented using approaches based on edge-detection or histogram analysis. With 1-µm resolution scans, the osteocyte lacunar spaces could be visualized, and it was possible to separate the lacunar porosity from the vascular porosity. At 4-µm resolution, the vascular porosity and vascular canal diameter were underestimated, and osteocyte lacunae were not effectively detected, whereas the vascular canal separation and tissue mineral density were overestimated compared to 1-µm resolution. Resolution had a much greater effect on the measurements than did threshold method, with partial volume effects at resolutions coarser than 2 µm demonstrated in two separate analyses, one of which assessed the effect of resolution on an object of known size with similar architecture to a vascular pore. Although there was little difference when using the edge-detection versus histogram-based threshold approaches, edge-detection was somewhat more effective in delineating canal architecture at finer resolutions (1 – 2 µm). In addition, use of a high-resolution (1-µm) density-based threshold on lower resolution (4-µm) density-calibrated images was not effective in improving the lower-resolution measurements. In conclusion, if measuring cortical vascular microarchitecture

  19. High Level of Vector Competence of Aedes aegypti and Aedes albopictus from Ten American Countries as a Crucial Factor in the Spread of Chikungunya Virus

    PubMed Central

    Vega-Rúa, Anubis; Zouache, Karima; Girod, Romain

    2014-01-01

    ABSTRACT Chikungunya virus (CHIKV) causes a major public health problem. In 2004, CHIKV began an unprecedented global expansion and has been responsible for epidemics in Africa, Asia, islands in the Indian Ocean region, and surprisingly, in temperate regions, such as Europe. Intriguingly, no local transmission of chikungunya virus (CHIKV) had been reported in the Americas until recently, despite the presence of vectors and annually reported imported cases. Here, we assessed the vector competence of 35 American Aedes aegypti and Aedes albopictus mosquito populations for three CHIKV genotypes. We also compared the number of viral particles of different CHIKV strains in mosquito saliva at two different times postinfection. Primarily, viral dissemination rates were high for all mosquito populations irrespective of the tested CHIKV isolate. In contrast, differences in transmission efficiency (TE) were underlined in populations of both species through the Americas, suggesting the role of salivary glands in selecting CHIKV for highly efficient transmission. Nonetheless, both mosquito species were capable of transmitting all three CHIKV genotypes, and TE reached alarming rates as high as 83.3% and 96.7% in A. aegypti and A. albopictus populations, respectively. A. albopictus better transmitted the epidemic mutant strain CHIKV_0621 of the East-Central-South African (ECSA) genotype than did A. aegypti, whereas the latter species was more capable of transmitting the original ECSA CHIKV_115 strain and also the Asian genotype CHIKV_NC. Therefore, a high risk of establishment and spread of CHIKV throughout the tropical, subtropical, and even temperate regions of the Americas is more real than ever. IMPORTANCE Until recently, the Americas had never reported chikungunya (CHIK) autochthonous transmission despite its global expansion beginning in 2004. Large regions of the continent are highly infested with Aedes aegypti and Aedes albopictus mosquitoes, and millions of dengue (DEN

  20. Potential spread of highly pathogenic avian influenza H5N1 by wildfowl: dispersal ranges and rates determined from large-scale satellite telemetry

    USGS Publications Warehouse

    Gaidet, Nicolas; Cappelle, Julien; Takekawa, John Y.; Prosser, Diann J.; Iverson, Samuel A.; Douglas, David C.; Perry, William M.; Mundkur, Taej; Newman, Scott H.

    2010-01-01

    1. Migratory birds are major candidates for long-distance dispersal of zoonotic pathogens. In recent years, wildfowl have been suspected of contributing to the rapid geographic spread of the highly pathogenic avian influenza (HPAI) H5N1 virus. Experimental infection studies reveal that some wild ducks, geese and swans shed this virus asymptomatically and hence have the potential to spread it as they move. 2. We evaluate the dispersive potential of HPAI H5N1 viruses by wildfowl through an analysis of the movement range and movement rate of birds monitored by satellite telemetry in relation to the apparent asymptomatic infection duration (AID) measured in experimental studies. We analysed the first large-scale data set of wildfowl movements, including 228 birds from 19 species monitored by satellite telemetry in 2006–2009, over HPAI H5N1 affected regions of Asia, Europe and Africa. 3. Our results indicate that individual migratory wildfowl have the potential to disperse HPAI H5N1 over extensive distances, being able to perform movements of up to 2900 km within timeframes compatible with the duration of asymptomatic infection. 4. However, the likelihood of such virus dispersal over long distances by individual wildfowl is low: we estimate that for an individual migratory bird there are, on average, only 5–15 days per year when infection could result in the dispersal of HPAI H5N1 virus over 500 km. 5. Staging at stopover sites during migration is typically longer than the period of infection and viral shedding, preventing birds from dispersing a virus over several consecutive but interrupted long-distance movements. Intercontinental virus dispersion would therefore probably require relay transmission between a series of successively infected migratory birds. 6. Synthesis and applications. Our results provide a detailed quantitative assessment of the dispersive potential of HPAI H5N1 virus by selected migratory birds. Such dispersive potential rests on the

  1. Detonation spreading in fine TATBs

    SciTech Connect

    Kennedy, J.E.; Lee, K.Y.; Spontarelli, T.; Stine, J.R.

    1998-12-31

    A test has been devised that permits rapid evaluation of the detonation-spreading (or corner-turning) properties of detonations in insensitive high explosives. The test utilizes a copper witness plate as the medium to capture performance data. Dent depth and shape in the copper are used as quantitative measures of the detonation output and spreading behavior. The merits of the test are that it is easy to perform with no dynamic instrumentation, and the test requires only a few grams of experimental explosive materials.

  2. High yield primary microglial cultures using granulocyte macrophage-colony stimulating factor from embryonic murine cerebral cortical tissue.

    PubMed

    Yu, Adam C; Neil, Sarah E; Quandt, Jacqueline A

    2017-06-15

    Microglia play vital roles in neurotrophic support and modulating immune or inflammatory responses to pathogens or damage/stressors during disease. This study describes the ability to establish large numbers of microglia from embryonic tissues with the addition of granulocyte-macrophage stimulating factor (GM-CSF) and characterizes their similarities to adult microglia examined ex vivo as well as their responses to inflammatory mediators. Microglia were seeded from a primary embryonic mixed cortical suspension with the addition of GM-CSF. Microglial expression of CD45, CD11b, CD11c, MHC class I and II, CD40, CD80, and CD86 was analyzed by flow cytometry and compared to those isolated using different culture methods and to the BV-2 cell line. GM-CSF microglia immunoreactivity and cytokine production was examined in response to lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Our results demonstrate GM-CSF addition during microglial culture yields higher cell numbers with greater purity than conventionally cultured primary microglia. We found that the expression of immune markers by GM-CSF microglia more closely resemble adult microglia than other methods or an immortalized BV-2 cell line. Primary differences amongst the different groups were reflected in their levels of CD39, CD86 and MHC class I expression. GM-CSF microglia produce CCL2, tumor necrosis factor-α, IL-6 and IL-10 following exposure to LPS and alter costimulatory marker expression in response to LPS or IFN-γ. Notably, GM-CSF microglia were often more responsive than the commonly used BV-2 cell line which produced negligible IL-10. GM-CSF cultured microglia closely model the phenotype of adult microglia examined ex vivo. GM-CSF microglia are robust in their responses to inflammatory stimuli, altering immune markers including Iba-1 and expressing an array of cytokines characteristic of both pro-inflammatory and reparative processes. Consequently, the addition of GM-CSF for the culturing of primary

  3. A Cross-Sectional Study of the Relationship between Cortical Bone and High-Impact Activity in Young Adult Males and Females

    PubMed Central

    Deere, K.; Sayers, A.; Rittweger, J.

    2012-01-01

    Context: The factors that govern skeletal responses to physical activity remain poorly understood. Objective: The aim of this study was to investigate whether gender or fat mass influences relationships between cortical bone and physical activity, after partitioning accelerometer outputs into low (0.5–2.1 g), medium (2.1–4.2 g), or high (>4.2 g) impacts, where g represents gravitational force. Design/Setting: We conducted a cross-sectional analysis in participants from the Avon Longitudinal Study of Parents and Children. Participants: We studied 675 adolescents (272 boys; mean age, 17.7 yr). Outcome Measures: We measured cortical bone parameters from peripheral quantitative computed tomography scans of the mid-tibia, adjusted for height, fat mass, and lean mass. Results: High-impact activity was positively associated with periosteal circumference (PC) in males but not females [coefficients (95% confidence intervals), 0.054 (0.007, 0.100) and 0.07 (−0.028, 0.041), respectively; showing sd change per doubling in activity]. There was also weak evidence that medium impacts were positively related to PC in males but not females (P = 0.03 for gender interaction). On stratifying by fat mass, the positive relationship between high-impact activity and PC was greatest in those with the highest fat mass [high impact vs. PC in males, 0.01 (−0.064, 0.085), 0.045 (−0.040, 0.131), 0.098 (0.012, 0.185), for lower, middle, and upper fat tertiles, respectively; high impact vs. PC in females, −0.041 (−0.101, 0.020), −0.028 (−0.077, 0.022), 0.082 (0.015, 0.148), P = 0.01 for fat mass interaction]. Similar findings were observed for strength parameters, cross-sectional moment of inertia, and strength-strain index. Conclusions: In late adolescence, associations between high-impact activity and PC are attenuated by female gender and low body fat, suggesting that the skeletal response to high-impact activity is particularly reduced in young women with low fat mass. PMID

  4. B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

    PubMed Central

    Zang, Xingxing; Thompson, R. Houston; Al-Ahmadie, Hikmat A.; Serio, Angel M.; Reuter, Victor E.; Eastham, James A.; Scardino, Peter T.; Sharma, Padmanee; Allison, James P.

    2007-01-01

    B7-H3 and B7x are recently discovered members of the B7-CD28 family thought to dampen peripheral immune responses via negative costimulation. We evaluated their potential expression in human prostate cancer using a large cohort of patients with 7 years of follow-up. We identified 823 patients with tissue available treated with radical prostatectomy between 1985 and 2003. Immunohistochemistry was performed on tissue microarray sections using anti-B7-H3 and -B7x. The percentage and intensity of immunoreactivity by tumor cells were blindly evaluated by two urological pathologists, and outcome analyses were conducted. Both B7-H3 and B7x were highly expressed; 93% and 99% of tumors had aberrant expression, respectively. The median percentage of tumor cells staining positive was 80% for each molecule. Strong intensity for B7-H3 and B7x was noted in 212 (26%) and 120 (15%) patients, respectively. Patients with strong intensity for B7-H3 and B7x were significantly more likely to have disease spread at time of surgery (P < 0.001 and P = 0.005, respectively). Additionally, patients with strong intensity for B7-H3 and B7x were at significantly increased risk of clinical cancer recurrence (P < 0.001 and P = 0.005) and cancer-specific death (P = 0.004 and P = 0.04, respectively). To our knowledge, we present the largest investigation of B7 family molecules in a human malignancy and a previously undescribed evaluation of B7x in prostate cancer. B7-H3 and B7x are abundantly expressed in prostate cancer and associated with disease spread and poor outcome. Given the proposed immune-inhibitory mechanisms of B7-H3 and B7x, these molecules represent attractive targets for therapeutic manipulation in prostate cancer. PMID:18042703

  5. High-resolution surveys along the hot spot-affected Gálapagos Spreading Center: 3. Black smoker discoveries and the implications for geological controls on hydrothermal activity

    NASA Astrophysics Data System (ADS)

    Haymon, Rachel M.; White, Scott M.; Baker, Edward T.; Anderson, Peter G.; MacDonald, Ken C.; Resing, Joseph A.

    2008-12-01

    To explore effects of hot spots on mid-ocean ridge hydrothermal systems, we conducted nested sonar, hydrothermal plume, and near-bottom photographic surveys along the portion of the Galápagos Spreading Center (GSC) influenced by the Galápagos hot spot, from longitude 95°-89.5°W. We report the first active high-temperature black smokers to be found on the GSC, at longitudes 94°4.5'W and 91°56.2'-54.3'W; describe two areas of recently inactive smokers, at longitudes 91°23.4'-23.7'W and 91°13.8'W; and document an older inactive site, at longitude 90°33.4'W. All imaged vents issue either from dike-induced fissures along linear axial volcanic ridges and collapses or from a caldera. Magmatic control of hydrothermal systems also is revealed by spatial clustering of plumes within the topographically elevated middles of volcanic ridge segments with inferred centralized melt supply. In searched areas, smokers are more typical than diffuse flow vents, but total GSC plume incidence is half of that expected from the spreading rate. Why? Dike-fed fissures provide permeable pathways for efficient hydrothermal extraction of magmatic heat, but cones without calderas do not. Among many point-source cones surveyed, only the two with calderas had detectable plumes. Possibly, dominance of point-source over linear-source melt delivery on the GSC decreases plume incidence. Also, similar maturities of observed vents and their host lava flows indicate that hydrothermally active volcanic segments along the western GSC are contemporaneously in a waning phase of volcanic-hydrothermal activity. Perhaps ridge/hot spot interaction produces melt pulses that drive near-synchronous volcanic-hydrothermal activity on the volcanic segments spanning the hot spot. During active periods, hydrothermally active dike-fed fissures and calderas may be more abundant than we currently observe.

  6. Satellite Tracking on the Flyways of Brown-Headed Gulls and Their Potential Role in the Spread of Highly Pathogenic Avian Influenza H5N1 Virus

    PubMed Central

    Ratanakorn, Parntep; Wiratsudakul, Anuwat; Wiriyarat, Witthawat; Eiamampai, Krairat; Farmer, Adrian H.; Webster, Robert G.; Chaichoune, Kridsada; Suwanpakdee, Sarin; Pothieng, Duangrat; Puthavathana, Pilaipan

    2012-01-01

    Brown-headed gulls (Larus brunnicephalus), winter visitors of Thailand, were tracked by satellite telemetry during 2008–2011 for investigating their roles in the highly pathogenic avian influenza (HPAI) H5N1 virus spread. Eight gulls negative for influenza virus infection were marked with solar-powered satellite platform transmitters at Bang Poo study site in Samut Prakarn province, Thailand; their movements were monitored by the Argos satellite tracking system, and locations were mapped. Five gulls completed their migratory cycles, which spanned 7 countries (China, Bangladesh, India, Myanmar, Thailand, Cambodia, and Vietnam) affected by the HPAI H5N1 virus. Gulls migrated from their breeding grounds in China to stay overwinter in Thailand and Cambodia; while Bangladesh, India, Myanmar, and Vietnam were the places of stopovers during migration. Gulls traveled an average distance of about 2400 km between Thailand and China and spent 1–2 weeks on migration. Although AI surveillance among gulls was conducted at the study site, no AI virus was isolated and no H5N1 viral genome or specific antibody was detected in the 75 gulls tested, but 6.6% of blood samples were positive for pan-influenza A antibody. No AI outbreaks were reported in areas along flyways of gulls in Thailand during the study period. Distance and duration of migration, tolerability of the captive gulls to survive the HPAI H5N1 virus challenge and days at viral shedding after the virus challenging suggested that the Brown-headed gull could be a potential species for AI spread, especially among Southeast Asian countries, the epicenter of H5N1 AI outbreak. PMID:23209623

  7. Satellite tracking on the flyways of brown-headed gulls and their potential role in the spread of highly pathogenic avian influenza H5N1 virus.

    PubMed

    Ratanakorn, Parntep; Wiratsudakul, Anuwat; Wiriyarat, Witthawat; Eiamampai, Krairat; Farmer, Adrian H; Webster, Robert G; Chaichoune, Kridsada; Suwanpakdee, Sarin; Pothieng, Duangrat; Puthavathana, Pilaipan

    2012-01-01

    Brown-headed gulls (Larus brunnicephalus), winter visitors of Thailand, were tracked by satellite telemetry during 2008-2011 for investigating their roles in the highly pathogenic avian influenza (HPAI) H5N1 virus spread. Eight gulls negative for influenza virus infection were marked with solar-powered satellite platform transmitters at Bang Poo study site in Samut Prakarn province, Thailand; their movements were monitored by the Argos satellite tracking system, and locations were mapped. Five gulls completed their migratory cycles, which spanned 7 countries (China, Bangladesh, India, Myanmar, Thailand, Cambodia, and Vietnam) affected by the HPAI H5N1 virus. Gulls migrated from their breeding grounds in China to stay overwinter in Thailand and Cambodia; while Bangladesh, India, Myanmar, and Vietnam were the places of stopovers during migration. Gulls traveled an average distance of about 2400 km between Thailand and China and spent 1-2 weeks on migration. Although AI surveillance among gulls was conducted at the study site, no AI virus was isolated and no H5N1 viral genome or specific antibody was detected in the 75 gulls tested, but 6.6% of blood samples were positive for pan-influenza A antibody. No AI outbreaks were reported in areas along flyways of gulls in Thailand during the study period. Distance and duration of migration, tolerability of the captive gulls to survive the HPAI H5N1 virus challenge and days at viral shedding after the virus challenging suggested that the Brown-headed gull could be a potential species for AI spread, especially among Southeast Asian countries, the epicenter of H5N1 AI outbreak.

  8. The spreading of disorder.

    PubMed

    Keizer, Kees; Lindenberg, Siegwart; Steg, Linda

    2008-12-12

    Imagine that the neighborhood you are living in is covered with graffiti, litter, and unreturned shopping carts. Would this reality cause you to litter more, trespass, or even steal? A thesis known as the broken windows theory suggests that signs of disorderly and petty criminal behavior trigger more disorderly and petty criminal behavior, thus causing the behavior to spread. This may cause neighborhoods to decay and the quality of life of its inhabitants to deteriorate. For a city government, this may be a vital policy issue. But does disorder really spread in neighborhoods? So far there has not been strong empirical support, and it is not clear what constitutes disorder and what may make it spread. We generated hypotheses about the spread of disorder and tested them in six field experiments. We found that, when people observe that others violated a certain social norm or legitimate rule, they are more likely to violate other norms or rules, which causes disorder to spread.

  9. Flame spread across liquids

    NASA Technical Reports Server (NTRS)

    Ross, Howard D.; Miller, Fletcher; Schiller, David; Sirignano, William

    1995-01-01

    Recent reviews of our understanding of flame spread across liquids show that there are many unresolved issues regarding the phenomenology and causal mechanisms affecting ignition susceptibility, flame spread characteristics, and flame spread rates. One area of discrepancy is the effect of buoyancy in both the uniform and pulsating spread regimes. The approach we have taken to resolving the importance of buoyancy for these flames is: (1) normal gravity (1g) and microgravity (micro g) experiments; and (2) numerical modeling at different gravitational levels. Of special interest to this work, as discussed at the previous workshop, is the determination of whether, and under what conditions, pulsating spread occurs in micro g. Microgravity offers a unique ability to modify and control the gas-phase flow pattern by utilizing a forced air flow over the pool surface.

  10. Altered Cortical Responsiveness to Pain Stimuli after High Frequency Electrical Stimulation of the Skin in Patients with Persistent Pain after Inguinal Hernia Repair

    PubMed Central

    van den Broeke, Emanuel N.; Koeslag, Lonneke; Arendsen, Laura J.; Nienhuijs, Simon W.; Rosman, Camiel; van Rijn, Clementina M.; Wilder-Smith, Oliver H. G.; van Goor, Harry

    2013-01-01

    Background High Frequency electrical Stimulation (HFS) of the skin induces enhanced brain responsiveness expressed as enhanced Event-Related Potential (ERP) N1 amplitude to stimuli applied to the surrounding unconditioned skin in healthy volunteers. The aim of the present study was to investigate whether this enhanced ERP N1 amplitude could be a potential marker for altered cortical sensory processing in patients with persistent pain after surgery. Materials and Methods Nineteen male patients; 9 with and 10 without persistent pain after inguinal hernia repair received HFS. Before, directly after and thirty minutes after HFS evoked potentials and the subjective pain intensity were measured in response to electric pain stimuli applied to the surrounding unconditioned skin. Results The results show that, thirty minutes after HFS, the ERP N1 amplitude observed at the conditioned arm was statistically significantly larger than the amplitude at the control arm across all patients. No statistically significant differences were observed regarding ERP N1 amplitude between patients with and without persistent pain. However, thirty minutes after HFS we did observe statistically significant differences of P2 amplitude at the conditioned arm between the two groups. The P2 amplitude decreased in comparison to baseline in the group of patients with pain. Conclusion The ERP N1 effect, induced after HFS, was not different between patients with vs. without persistent pain. The decreasing P2 amplitude was not observed in the patients without pain and also not in the previous healthy volunteer study and thus might be a marker for altered cortical sensory processing in patients with persistent pain after surgery. PMID:24376568

  11. Sedation Agents Differentially Modulate Cortical and Subcortical Blood Oxygenation: Evidence from Ultra-High Field MRI at 17.2 T

    PubMed Central

    Uhrig, Lynn; Ciobanu, Luisa; Djemai, Boucif; Le Bihan, Denis; Jarraya, Béchir

    2014-01-01

    Background Sedation agents affect brain hemodynamic and metabolism leading to specific modifications of the cerebral blood oxygenation level. We previously demonstrated that ultra-high field (UHF) MRI detects changes in cortical blood oxygenation following the administration of sedation drugs commonly used in animal research. Here we applied the UHF-MRI method to study clinically relevant sedation drugs for their effects on cortical and subcortical (thalamus, striatum) oxygenation levels. Methods We acquired T2*-weighted images of Sprague-Dawley rat brains at 17.2T in vivo. During each MRI session, rats were first anesthetized with isoflurane, then with a second sedative agent (sevoflurane, propofol, midazolam, medetomidine or ketamine-xylazine) after stopping isoflurane. We computed a T2*-oxygenation-ratio that aimed at estimating cerebral blood oxygenation level for each sedative agent in each region of interest: cortex, hippocampus, thalamus and striatum. Results The T2*-oxygenation-ratio was consistent across scan sessions. This ratio was higher with inhalational agents than with intravenous agents. Under sevoflurane and medetomidine, T2*-oxygenation-ratio was homogenous across the brain regions. Intravenous agents (except medetomidine) induced a T2*-oxygenation-ratio imbalance between cortex and subcortical regions: T2*-oxygenation-ratio was higher in the cortex than the subcortical areas under ketamine-xylazine; T2*-oxygenation-ratio was higher in subcortical regions than in the cortex under propofol or midazolam. Conclusion Preclinical UHF MRI is a powerful method to monitor the changes in cerebral blood oxygenation level induced by sedative agents across brain structures. This approach also allows for a classification of sedative agents based on their differential effects on cerebral blood oxygenation level. PMID:25050866

  12. High expression of podoplanin in squamous cell carcinoma of the tongue occurs predominantly in patients ≤40 years but does not correlate with tumour spread

    PubMed Central

    Lindell Jonsson, Eva; Boldrup, Linda; Califano, Luigi; Coates, Philip J; Tartaro, Gianpaolo; Lo Muzio, Lorenzo; Fåhraeus, Robin; Colella, Giuseppe; Dell'Aversana Orabona, Giovanni; Loljung, Lotta; Santagata, Mario; Rossiello, Riccardo; Wilms, Torben; Danielsson, Karin; Laurell, Göran

    2015-01-01

    Abstract More than 30% of patients with squamous cell carcinoma (SCC) of the mobile tongue have clinically undetectable lymph node metastasis. Tumour cells can spread as single cells or collectively. A protein known to play a role in both processes is podoplanin, which is expressed in endothelial cells not only in lymph vessels but also in some aggressive tumours with high invasive and metastatic potential. Here we studied samples from 129 patients with primary SCC of the tongue for expression of podoplanin using immunohistochemistry. mRNA levels were analysed in another 27 cases of tongue SCC with adjacent clinically tumour‐free tongue tissue and 14 tongue samples from healthy donors. Higher levels of podoplanin were seen in tumours compared to both normal tongue and clinically normal tongue in the tumour vicinity. No association was found between levels of podoplanin, presence of lymph node metastases or other clinical factors. Patients aged 40 or less were more likely to express high levels of podoplanin protein compared to older patients (p = 0.027). We conclude that levels of podoplanin in primary tongue SCCs are not associated with lymph node metastases. However, tongue SCCs arising in young patients (≤40 years of age) are more likely to express high levels of podoplanin than tongue SCCs that arise in the more elderly. The data suggest that podoplanin has a distinctive role in young patients, who are known to have a poor prognosis: these patients may, therefore, benefit from podoplanin inhibitory therapies. PMID:27499910

  13. High expression of podoplanin in squamous cell carcinoma of the tongue occurs predominantly in patients ≤40 years but does not correlate with tumour spread.

    PubMed

    Sgaramella, Nicola; Lindell Jonsson, Eva; Boldrup, Linda; Califano, Luigi; Coates, Philip J; Tartaro, Gianpaolo; Lo Muzio, Lorenzo; Fåhraeus, Robin; Colella, Giuseppe; Dell'Aversana Orabona, Giovanni; Loljung, Lotta; Santagata, Mario; Rossiello, Riccardo; Wilms, Torben; Danielsson, Karin; Laurell, Göran; Nylander, Karin

    2016-01-01

    More than 30% of patients with squamous cell carcinoma (SCC) of the mobile tongue have clinically undetectable lymph node metastasis. Tumour cells can spread as single cells or collectively. A protein known to play a role in both processes is podoplanin, which is expressed in endothelial cells not only in lymph vessels but also in some aggressive tumours with high invasive and metastatic potential. Here we studied samples from 129 patients with primary SCC of the tongue for expression of podoplanin using immunohistochemistry. mRNA levels were analysed in another 27 cases of tongue SCC with adjacent clinically tumour-free tongue tissue and 14 tongue samples from healthy donors. Higher levels of podoplanin were seen in tumours compared to both normal tongue and clinically normal tongue in the tumour vicinity. No association was found between levels of podoplanin, presence of lymph node metastases or other clinical factors. Patients aged 40 or less were more likely to express high levels of podoplanin protein compared to older patients (p = 0.027). We conclude that levels of podoplanin in primary tongue SCCs are not associated with lymph node metastases. However, tongue SCCs arising in young patients (≤40 years of age) are more likely to express high levels of podoplanin than tongue SCCs that arise in the more elderly. The data suggest that podoplanin has a distinctive role in young patients, who are known to have a poor prognosis: these patients may, therefore, benefit from podoplanin inhibitory therapies.

  14. Flame Spread Across Liquids

    NASA Technical Reports Server (NTRS)

    Ross, Howard D.; Miller, Fletcher J.; Sirignano, William A.; Schiller, David

    1997-01-01

    The principal goal of our recent research on flame spread across liquid pools is the detailed identification of the mechanisms that control the rate and nature of flame spread when the liquid pool is initially at an isothermal bulk temperature that is below the fuel's flash point temperature. In our project, we specialize the subject to highlight the roles of buoyancy-related processes regarding the mechanisms of flame spread, an area of research cited recently by Linan and Williams as one that needs further attention and which microgravity (micro-g) experiments could help to resolve. Toward resolving the effects of buoyancy on this flame spread problem, comparisons - between 1-g and micro-g experimental observations, and between model predictions and experimental data at each of these gravitational levels - are extensively utilized. The present experimental and computational foundation is presented to support identification of the mechanisms that control flame spread in the pulsating flame spread regime for which long-duration, micro-g flame spread experiments have been conducted aboard a sounding rocket.

  15. Development of cortical motor circuits between childhood and adulthood: A navigated TMS-HdEEG study.

    PubMed

    Määttä, Sara; Könönen, Mervi; Kallioniemi, Elisa; Lakka, Timo; Lintu, Niina; Lindi, Virpi; Ferreri, Florinda; Ponzo, David; Säisänen, Laura

    2017-02-20

    Motor functions improve during childhood and adolescence, but little is still known about the development of cortical motor circuits during early life. To elucidate the neurophysiological hallmarks of motor cortex development, we investigated the differences in motor cortical excitability and connectivity between healthy children, adolescents, and adults by means of navigated suprathreshold motor cortex transcranial magnetic stimulation (TMS) combined with high-density electroencephalography (EEG). We demonstrated that with development, the excitability of the motor system increases, the TMS-evoked EEG waveform increases in complexity, the magnitude of induced activation decreases, and signal spreading increases. Furthermore, the phase of the oscillatory response to TMS becomes less consistent with age. These changes parallel an improvement in manual dexterity and may reflect developmental changes in functional connectivity. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  16. Automatic Sulcal Curve Extraction on the Human Cortical Surface

    PubMed Central

    Lyu, Ilwoo; Kim, Sun Hyung; Styner, Martin

    2015-01-01

    The recognition of sulcal regions on the cortical surface is an important task to shape analysis and landmark detection. However, it is challenging especially in a complex, rough human cortex. In this paper, we focus on the extraction of sulcal curves from the human cortical surface. The previous sulcal extraction methods are time-consuming in practice and often have a difficulty to delineate curves correctly along the sulcal regions in the presence of significant noise. Our pipeline is summarized in two main steps: 1) We extract candidate sulcal points spread over the sulcal regions. We further reduce the size of the candidate points by applying a line simplification method. 2) Since the candidate points are potentially located away from the exact valley regions, we propose a novel approach to connect candidate sulcal points so as to obtain a set of complete curves (line segments). We have shown in experiment that our method achieves high computational efficiency, improved robustness to noise, and high reliability in a test-retest situation as compared to a well-known existing method. PMID:26028801

  17. Motor cortical organization in an adult with hemimegalencephaly and late onset epilepsy.

    PubMed

    Civardi, Carlo; Vicentini, Roberta; Collini, Alessandra; Boccagni, Cristina; Cantello, Roberto; Monaco, Francesco

    2009-08-28

    Hemimegalencephaly is a rare brain malformation whose physiology is largely obscure. In a single patient, we studied motor cortex using several transcranial magnetic stimulation variables testing cortical excitability, and mapping motor area. The megalencephalic hemisphere showed an enlargement of cortical motor map with abnormal axonal orientation and an excess spread of corticospinal excitation, associated with multiple defects of cortical inhibition. TMS gave new information on the anatomic/functional features and epileptogenesis in this complex and physiologically obscure syndrome.

  18. Quantum Spread Spectrum Communication

    SciTech Connect

    Humble, Travis S

    2010-01-01

    We demonstrate that spectral teleportation can coherently dilate the spectral probability amplitude of a single photon. In preserving the encoded quantum information, this variant of teleportation subsequently enables a form of quantum spread spectrum communication.

  19. Can high-temperature, high-heat flux hydrothermal vent fields be explained by thermal convection in the lower crust along fast-spreading Mid-Ocean Ridges?

    NASA Astrophysics Data System (ADS)

    Fontaine, Fabrice J.; Rabinowicz, M.; Cannat, M.

    2017-05-01

    We present numerical models to explore possible couplings along the axis of fast-spreading ridges, between hydrothermal convection in the upper crust and magmatic flow in the lower crust. In an end-member category of models corresponding to effective viscosities μM lower than 1013 Pa.s in a melt-rich lower crustal along-axis corridor and permeability k not exceeding ˜10-16 m2 in the upper crust, the hot, melt-rich, gabbroic lower crust convects as a viscous fluid, with convection rolls parallel to the ridge axis. In these models, we show that the magmatic-hydrothermal interface settles at realistic depths for fast ridges, i.e., 1-2 km below seafloor. Convection cells in both horizons are strongly coupled and kilometer-wide hydrothermal upflows/plumes, spaced by 8-10 km, arise on top of the magmatic upflows. Such magmatic-hydrothermal convective couplings may explain the distribution of vent fields along the East (EPR) and South-East Pacific Rise (SEPR). The lower crustal plumes deliver melt locally at the top of the magmatic horizon possibly explaining the observed distribution of melt-rich regions/pockets in the axial melt lenses of EPR and SEPR. Crystallization of this melt provides the necessary latent heat to sustain permanent ˜100 MW vents fields. Our models also contribute to current discussions on how the lower crust forms at fast ridges: they provide a possible mechanism for focused transport of melt-rich crystal mushes from moho level to the axial melt lens where they further crystallize, feed eruptions, and are transported both along and off-axis to produce the lower crust.

  20. Movement, confusion, and orienting in frontal cortices.

    PubMed

    Brecht, Michael

    2011-10-20

    In this issue, two studies, by Ehrlich et al. and Hill et al., address the role of the frontal motor cortices in behavior of the rat and suggest a potential role for this structure in high-level control of diverse behaviors. Hill et al. show that motor cortical neurons predict whisker movements even without sensory feedback and that their activity reflects efferent control. Surprisingly, Ehrlich et al. report the participation of this same cortical region in the preparation and execution of orienting behaviors.

  1. Evolution of cortical neurogenesis.

    PubMed

    Abdel-Mannan, Omar; Cheung, Amanda F P; Molnár, Zoltán

    2008-03-18

    The neurons of the mammalian neocortex are organised into six layers. By contrast, the reptilian and avian dorsal cortices only have three layers which are thought to be equivalent to layers I, V and VI of mammals. Increased repertoire of mammalian higher cognitive functions is likely a result of an expanded cortical surface area. The majority of cortical cell proliferation in mammals occurs in the ventricular zone (VZ) and subventricular zone (SVZ), with a small number of scattered divisions outside the germinal zone. Comparative developmental studies suggest that the appearance of SVZ coincides with the laminar expansion of the cortex to six layers, as well as the tangential expansion of the cortical sheet seen within mammals. In spite of great variation and further compartmentalisation in the mitotic compartments, the number of neurons in an arbitrary cortical column appears to be remarkably constant within mammals. The current challenge is to understand how the emergence and elaboration of the SVZ has contributed to increased cortical cell diversity, tangential expansion and gyrus formation of the mammalian neocortex. This review discusses neurogenic processes that are believed to underlie these major changes in cortical dimensions in vertebrates.

  2. Glucose modulation of spreading depression susceptibility

    PubMed Central

    Hoffmann, Ulrike; Sukhotinsky, Inna; Eikermann-Haerter, Katharina; Ayata, Cenk

    2013-01-01

    Spreading depression of Leão is an intense spreading depolarization (SD) wave associated with massive transmembrane ionic, water, and neurotransmitter shifts. Spreading depolarization underlies migraine aura, and occurs in brain injury, making it a potential therapeutic target. While susceptibility to SD can be modulated pharmacologically, much less is known about modulation by systemic physiological factors, such as the glycemic state. In this study, we systematically examined modulation of SD susceptibility by blood glucose in anesthetized rats under full physiological monitoring. Hyperglycemia and hypoglycemia were induced by insulin or dextrose infusion (blood glucose ∼40 and 400 mg/dL, respectively). Spreading depolarizations were evoked by direct cortical electrical stimulation to determine the intensity threshold, or by continuous topical KCl application to determine SD frequency. Hyperglycemia elevated the electrical SD threshold and reduced the frequency of KCl-induced SDs, without significantly affecting other SD properties. In contrast, hypoglycemia significantly prolonged individual and cumulative SD durations, but did not alter the electrical SD threshold, or SD frequency, amplitude or propagation speed. These data show that increased cerebral glucose availability makes the tissue resistant to SD. PMID:22968322

  3. The universal dynamics of cell spreading.

    PubMed

    Cuvelier, Damien; Théry, Manuel; Chu, Yeh-Shiu; Dufour, Sylvie; Thiéry, Jean-Paul; Bornens, Michel; Nassoy, Pierre; Mahadevan, L

    2007-04-17

    Cell adhesion and motility depend strongly on the interactions between cells and extracellular matrix (ECM) substrates. When plated onto artificial adhesive surfaces, cells first flatten and deform extensively as they spread. At the molecular level, the interaction of membrane-based integrins with the ECM has been shown to initiate a complex cascade of signaling events [1], which subsequently triggers cellular morphological changes and results in the generation of contractile forces [2]. Here, we focus on the early stages of cell spreading and probe their dynamics by quantitative visualization and biochemical manipulation with a variety of cell types and adhesive surfaces, adhesion receptors, and cytoskeleton-altering drugs. We find that the dynamics of adhesion follows a universal power-law behavior. This is in sharp contrast with the common belief that spreading is regulated by either the diffusion of adhesion receptors toward the growing adhesive patch [3-5] or by actin polymerization [6-8]. To explain this, we propose a simple quantitative and predictive theory that models cells as viscous adhesive cortical shells enclosing a less viscous interior. Thus, although cell spreading is driven by well-identified biomolecular interactions, it is dynamically limited by its mesoscopic structure and material properties.

  4. The Cortical Peptidoglycan from Spores of Bacillus Megaterium and Bacillus Subtilis Is Not Highly Cross-Linked

    DTIC Science & Technology

    1993-05-01

    Bacilius megaterium and Bacillus subtilis Is Not Highly Cross-Linked 6. AUTHOR(S) David L. Popham and Peter Setlow 7. PERFORMING ORGANIZATION NAME(S...Determination by amino acid analyses of the percentage of diaminopimelic acid in the spore cortex of Bacillus megaterium and Bacillus subtilis which is...Peptidoglycan from Spores of Bacillus megaterium and Bacillus subtilis Is Not Highly Cross-Linked DAVID L. POPHAM ANDl PETER SETLOW* Department of Biochemistry

  5. High-resolution magnetic signature of active hydrothermal systems in the back-arc spreading region of the southern Mariana Trough

    NASA Astrophysics Data System (ADS)

    Fujii, Masakazu; Okino, Kyoko; Honsho, Chie; Dyment, Jerome; Szitkar, Florent; Mochizuki, Nobutatsu; Asada, Miho

    2015-05-01

    High-resolution vector magnetic measurements were performed on five hydrothermal vent fields of the back-arc spreading region of the southern Mariana Trough using Shinkai 6500, a deep-sea manned submersible. A new 3-D forward scheme was applied that exploits the surrounding bathymetry and varying altitudes of the submersible to estimate absolute crustal magnetization. The results revealed that magnetic-anomaly-derived absolute magnetizations show a reasonable correlation with natural remanent magnetizations of rock samples collected from the seafloor of the same region. The distribution of magnetic-anomaly-derived absolute magnetization suggests that all five andesite-hosted hydrothermal fields are associated with a lack of magnetization, as is generally observed at basalt-hosted hydrothermal sites. Furthermore, both the Pika and Urashima sites were found to have their own distinct low-magnetization zones, which could not be distinguished in magnetic anomaly data collected at higher altitudes by autonomous underwater vehicle due to their limited extension. The spatial extent of the resulting low magnetization is approximately 10 times wider at off-axis sites than at on-axis sites, possibly reflecting larger accumulations of nonmagnetic sulfides, stockwork zones, and/or alteration zones at the off-axis sites.

  6. High-resolution Remotely Operated Vehicle (ROV) mapping of a slow-spreading ridge: Mid-Atlantic Ridge 45°N

    NASA Astrophysics Data System (ADS)

    Yeo, I. A.; Searle, R. C.

    2013-06-01

    Axial volcanic ridges (AVRs) are found on most slow-spreading mid-ocean ridges and are thought to be the main locus of volcanism there. In this study we present high-resolution mapping of a typical, well-defined AVR on the Mid-Atlantic Ridge at 45°N. The AVR is characterized by "hummocky terrain," composed typically of hummocks with pillowed or elongate pillowed flanks with pillowed or lobate lava flow summits, often with small haystacks sitting on their highest points. The AVR is surrounded by several areas of "flat seafloor," composed of lobate and sheet lava flows. The spatial and morphological differences between these areas indicate different eruption processes operating on and off the AVR. Volcanic fissures are found all around and on the AVR, although those with the greatest horizontal displacement are found on the ridge crest and flat seafloor. Clusters of fissures may represent volcanic vents. Extremely detailed comparisons of sediment coverage and examination of contact relations around the AVR suggest that many of the areas of flat seafloor are of a similar age or younger than the hummocky terrain of the AVR. Additionally, all the lavas surveyed have similar degrees of sediment cover, suggesting that the AVR was either built or resurfaced in the same 50 ka time frame as the flat seafloor.

  7. The limits of seaward spreading and slope instability at the continental margin offshore Mt Etna, imaged by high-resolution 2D seismic data

    NASA Astrophysics Data System (ADS)

    Gross, Felix; Krastel, Sebastian; Geersen, Jacob; Behrmann, Jan Hinrich; Ridente, Domenico; Chiocci, Francesco Latino; Bialas, Jörg; Papenberg, Cord; Cukur, Deniz; Urlaub, Morelia; Micallef, Aaron

    2016-01-01

    Mount Etna is the largest active volcano in Europe. Instability of its eastern flank is well documented onshore, and continuously monitored by geodetic and InSAR measurements. Little is known, however, about the offshore extension of the eastern volcano flank, defining a serious shortcoming in stability models. In order to better constrain the active tectonics of the continental margin offshore the eastern flank of the volcano, we acquired a new high-resolution 2D reflection seismic dataset. The data provide new insights into the heterogeneous geology and tectonics at the continental margin offshore Mt Etna. The submarine realm is characterized by different blocks, which are controlled by local- and regional tectonics. A compressional regime is found at the toe of the continental margin, which is bound to a complex basin system. Both, the clear link between on- and offshore tectonic structures as well as the compressional regime at the easternmost flank edge, indicate a continental margin gravitational collapse as well as spreading to be present at Mt Etna. Moreover, we find evidence for the offshore southern boundary of the moving flank, which is identified as a right lateral oblique fault north of Catania Canyon. Our findings suggest a coupled volcano edifice/continental margin instability at Mt Etna, demonstrating first order linkage between on- and offshore tectonic processes.

  8. Agro-ecological features of the introduction and spread of the highly pathogenic avian influenza (HPAI) H5N1 in northern Nigeria.

    PubMed

    Cecchi, Giuliano; Ilemobade, Albert; Le Brun, Yvon; Hogerwerf, Lenny; Slingenbergh, Jan

    2008-11-01

    Nigeria was the first African country to report highly pathogenic avian influenza (HPAI) H5N1 virus outbreaks in February 2006 and has since been the most severely hit country in sub-Saharan Africa. A retrospective survey carried out towards the end of 2007, coupled with follow-up spatial analysis, support the notion that the H5N1 virus may have spread from rural areas of northern Nigeria near wetlands frequented by palaearctic migratory birds. Possibly, this could have happened already during November to December 2005, one or two months prior to the first officially reported outbreak in a commercial poultry farm (Kaduna state). It is plausible that backyard poultry played a more important role in the H5N1 propagation than thought previously. Farming landscapes with significant numbers of domestic ducks may have helped to bridge the geographical and ecological gap between the waterfowl in the wetlands and the densely populated poultry rich states in north-central Nigeria, where the virus had more sizeable, visible impact.

  9. Cortical Alterations in Medication-Overuse Headache.

    PubMed

    Riederer, Franz; Schaer, Marie; Gantenbein, Andreas R; Luechinger, Roger; Michels, Lars; Kaya, Marihan; Kollias, Spyridon; Sándor, Peter S

    2017-02-01

    Using surface-based morphometry we aimed to provide a detailed examination of cortical alterations in medication-overuse headache (MOH), by disentangling between altered cortical thickness and gyrification (folding). In MOH, pain modulation is probably dysfunctional at the cortical and subcortical level, resulting in a disequilibrium between pain inhibition and facilitation. Both increased and decreased cortical volumes have been reported in individuals with MOH. There is however no detailed examination to date that distinguishes between altered cortical thickness and gyrification. Such distinction would help to identify the nature and timing of neurodevelopmental mechanisms at play in affected individuals. We investigated cortical thickness and gyrification in 29 patients with MOH according to International Headache Society criteria and 29 age- and gender-matched controls, using high-resolution structural MRIs of the brain analyzed with FreeSurfer. This is a secondary analysis of data from a previously published voxel-based morphometry study. In patients with MOH compared to controls, reduced cortical thickness was observed in the left prefrontal cortex. We also observed higher local gyrification in one cluster extending from the fusiform cortex to adjacent medial temporal regions, and in another cluster in the right occipital pole. Higher gyrification in the right occipital pole predicted poor response after detoxification. Corroborating previous volumetric results, our study adds information on the putative neurobiological mechanisms involved in MOH, suggesting neurodevelopmental changes in MOH. © 2016 American Headache Society.

  10. Line-Bisecting Performance in Highly Skilled Athletes: Does Preponderance of Rightward Error Reflect Unique Cortical Organization and Functioning?

    ERIC Educational Resources Information Center

    Carlstedt, Roland A.

    2004-01-01

    A line-bisecting test was administered to 250 highly skilled right-handed athletes and a control group of 60 right-handed age matched non-athletes. Results revealed that athletes made overwhelmingly more rightward errors than non-athletes, who predominantly bisected lines to the left of the veridical center. These findings were interpreted in the…

  11. Line-Bisecting Performance in Highly Skilled Athletes: Does Preponderance of Rightward Error Reflect Unique Cortical Organization and Functioning?

    ERIC Educational Resources Information Center

    Carlstedt, Roland A.

    2004-01-01

    A line-bisecting test was administered to 250 highly skilled right-handed athletes and a control group of 60 right-handed age matched non-athletes. Results revealed that athletes made overwhelmingly more rightward errors than non-athletes, who predominantly bisected lines to the left of the veridical center. These findings were interpreted in the…

  12. Unstable Spreading of Ionic Liquids on an Aqueous Substrate.

    PubMed

    Tsuchitani, Shigeki; Fukutake, Taiga; Mukai, Daiki; Miki, Hirofumi; Kikuchi, Kunitomo

    2017-10-04

    The spontaneous spreading of thin liquid films over substrate surfaces is attracting much attention due to its broad applications. Under particular conditions, surfactants deposited on substrates exhibit unstable spreading. In spite of the large effects of the stability of the spreading on the accuracy and efficiency of industrial processes that use the spreading, understanding how the stability of the spreading process is governed by the physical and chemical properties of the system is still little known. Recently, ionic liquids have been characterized as a new kind of surfactant due to their special properties. Here, we investigate the stability of the spreading of deposited imidazolium-based ionic liquids on an aqueous substrate. We focus mainly on the effects that the water solubility of the ionic liquids has on the stability. Hydrophobic ionic liquids exhibit spreading that has a highly periodic and petal-like unstable spreading front, whereas hydrophilic ionic liquids spread without such a regular spreading front and their spreading area shrinks after reaching its maximum. We propose a model for the generation of unstable spreading of hydrophobic ionic liquids, i.e., the unstable spreading front is created by the penetration of oncoming water in front of the spreading tip into the more viscous spreading ionic liquid layer, like the viscous fingering that occurs in a Hele-Shaw cell. However, the direction of the penetration is the opposite of the direction that the interface moves (the spreading direction), which is contrary to that in viscous fingering.

  13. Expectancy of pain is influenced by motor preparation: a high-resolution EEG study of cortical alpha rhythms.

    PubMed

    Babiloni, Claudio; Brancucci, Alfredo; Capotosto, Paolo; Arendt-Nielsen, Lars; Chen, Andrew C N; Rossini, Paolo Maria

    2005-04-01

    This high-resolution electroencephalographic (EEG) study on alpha event-related desynchronization (ERD) evaluated whether anticipatory activity precedes a sensorimotor interaction induced by concomitant painful stimuli and sensorimotor demand. An omitted-stimulus paradigm induced the expectancy of the painful stimulation at the left hand. In the experimental condition, the painful stimulation was associated with a visual go/no-go task triggering right-hand movements. Two control conditions manipulated the painful sensorimotor interaction variable. Compared with the control conditions, the expectancy of the painful sensorimotor interaction increased the high-band alpha EEG oscillations over the right primary sensorimotor cortex contralateral to the nociceptive stimuli and, to a lesser extent, over the centroparietal midline. These findings suggest that concomitant painful stimuli and simple sensorimotor go/no-go demands affect anticipatory activity as revealed by alpha ERD.

  14. Precaution for volume conduction in rodent cortical electroencephalography using high-density polyimide-based microelectrode arrays on the skull

    PubMed Central

    Venzi, M.; Poppendieck, W.; Hoffmann, K. P.; Åberg, E.

    2016-01-01

    In humans, significant progress has been made to link spatial changes in electroencephalographic (EEG) spectral density, connectivity strength, and phase-amplitude modulation to neurological, physiological, and psychological correlates. In contrast, standard rodent EEG techniques employ only few electrodes, which results in poor spatial resolution. Recently, a technique was developed to overcome this limitation in mice. This technique was based on a polyimide-based microelectrode (PBM) array applied on the mouse skull, maintaining a significant number of electrodes with consistent contact, electrode impedance, and mechanical stability. The present study built on this technique by extending it to rats. Therefore, a similar PBM array, but adapted to rats, was designed and fabricated. In addition, this array was connected to a wireless EEG headstage, allowing recording in untethered, freely moving rats. The advantage of a high-density array relies on the assumption that the signal recorded from the different electrodes is generated from distinct sources, i.e., not volume-conducted. Therefore, the utility and validity of the array were evaluated by determining the level of synchrony between channels due to true synchrony or volume conduction during basal vigilance states and following a subanesthetic dose of ketamine. Although the PBM array allowed recording with high signal quality, under both drug and drug-free conditions, high synchronization existed due to volume conduction between the electrodes even in the higher spectral frequency range. Discrimination existed only between frontally and centrally/distally grouped electrode pairs. Therefore, caution should be used in interpreting spatial data obtained from high-density PBM arrays in rodents. PMID:26864767

  15. Precaution for volume conduction in rodent cortical electroencephalography using high-density polyimide-based microelectrode arrays on the skull.

    PubMed

    Stienen, P J; Venzi, M; Poppendieck, W; Hoffmann, K P; Åberg, E

    2016-04-01

    In humans, significant progress has been made to link spatial changes in electroencephalographic (EEG) spectral density, connectivity strength, and phase-amplitude modulation to neurological, physiological, and psychological correlates. In contrast, standard rodent EEG techniques employ only few electrodes, which results in poor spatial resolution. Recently, a technique was developed to overcome this limitation in mice. This technique was based on a polyimide-based microelectrode (PBM) array applied on the mouse skull, maintaining a significant number of electrodes with consistent contact, electrode impedance, and mechanical stability. The present study built on this technique by extending it to rats. Therefore, a similar PBM array, but adapted to rats, was designed and fabricated. In addition, this array was connected to a wireless EEG headstage, allowing recording in untethered, freely moving rats. The advantage of a high-density array relies on the assumption that the signal recorded from the different electrodes is generated from distinct sources, i.e., not volume-conducted. Therefore, the utility and validity of the array were evaluated by determining the level of synchrony between channels due to true synchrony or volume conduction during basal vigilance states and following a subanesthetic dose of ketamine. Although the PBM array allowed recording with high signal quality, under both drug and drug-free conditions, high synchronization existed due to volume conduction between the electrodes even in the higher spectral frequency range. Discrimination existed only between frontally and centrally/distally grouped electrode pairs. Therefore, caution should be used in interpreting spatial data obtained from high-density PBM arrays in rodents. Copyright © 2016 the American Physiological Society.

  16. Adaptive shaping of cortical response selectivity in the vibrissa pathway

    PubMed Central

    Zheng, He J. V.; Wang, Qi

    2015-01-01

    One embodiment of context-dependent sensory processing is bottom-up adaptation, where persistent stimuli decrease neuronal firing rate over hundreds of milliseconds. Adaptation is not, however, simply the fatigue of the sensory pathway, but shapes the information flow and selectivity to stimulus features. Adaptation enhances spatial discriminability (distinguishing stimulus location) while degrading detectability (reporting presence of the stimulus), for both the ideal observer of the cortex and awake, behaving animals. However, how the dynamics of the adaptation shape the cortical response and this detection and discrimination tradeoff is unknown, as is to what degree this phenomenon occurs on a continuum as opposed to a switching of processing modes. Using voltage-sensitive dye imaging in anesthetized rats to capture the temporal and spatial characteristics of the cortical response to tactile inputs, we showed that the suppression of the cortical response, in both magnitude and spatial spread, is continuously modulated by the increasing amount of energy in the adapting stimulus, which is nonuniquely determined by its frequency and velocity. Single-trial ideal observer analysis demonstrated a tradeoff between detectability and spatial discriminability up to a moderate amount of adaptation, which corresponds to the frequency range in natural whisking. This was accompanied by a decrease in both detectability and discriminability with high-energy adaptation, which indicates a more complex coupling between detection and discrimination than a simple switching of modes. Taken together, the results suggest that adaptation operates on a continuum and modulates the tradeoff between detectability and discriminability that has implications for information processing in ethological contexts. PMID:25787959

  17. Hypoxia in high glucose followed by reoxygenation in normal glucose reduces the viability of cortical astrocytes through increased permeability of connexin 43 hemichannels

    PubMed Central

    Orellana, Juan A.; Hernández, Diego E.; Ezan, Pascal; Velarde, Victoria; Bennett, Michael V. L.; Giaume, Christian; Sáez, Juan C.

    2009-01-01

    Brain ischemia causes more extensive injury in hyperglycemic than normoglycemic subjects, and the increased damage is to astroglia as well as neurons. In the present work, we found that in cortical astrocytes from rat or mouse, reoxygenation after hypoxia in a medium mimicking interstitial fluid during ischemia increases hemichannel activity and decreases cell-cell communication via gap junctions as indicated by dye uptake and dye coupling, respectively. These effects were potentiated by high glucose during the hypoxia in a concentration-dependent manner (and by zero glucose) and were not observed in connexin 43−/− astrocytes. The responses were transient or persistent after short and long periods of hypoxia, respectively. The persistent responses were associated with a progressive reduction in cell viability that was prevented by La3+ or peptides that block connexin 43 (Cx43) hemichannels or by inhibition of p38 MAP kinase prior to hypoxia-reoxygenation but not by treatments that block pannexin hemichannels. Block of Cx43 hemichannels did not affect the reduction in gap junction mediated dye coupling observed during reoxygenation. Cx43 hemichannels may be a novel therapeutic target to reduce cell death following stroke, particularly in hyperglycemic conditions. PMID:19705457

  18. Abnormal white matter tractography of visual pathways detected by high-angular-resolution diffusion imaging (HARDI) corresponds to visual dysfunction in cortical/cerebral visual impairment.

    PubMed

    Bauer, Corinna M; Heidary, Gena; Koo, Bang-Bon; Killiany, Ronald J; Bex, Peter; Merabet, Lotfi B

    2014-08-01

    Cortical (cerebral) visual impairment (CVI) is characterized by visual dysfunction associated with damage to the optic radiations and/or visual cortex. Typically it results from pre- or perinatal hypoxic damage to postchiasmal visual structures and pathways. The neuroanatomical basis of this condition remains poorly understood, particularly with regard to how the resulting maldevelopment of visual processing pathways relates to observations in the clinical setting. We report our investigation of 2 young adults diagnosed with CVI and visual dysfunction characterized by difficulties related to visually guided attention and visuospatial processing. Using high-angular-resolution diffusion imaging (HARDI), we characterized and compared their individual white matter projections of the extrageniculo-striate visual system with a normal-sighted control. Compared to a sighted control, both CVI cases revealed a striking reduction in association fibers, including the inferior frontal-occipital fasciculus as well as superior and inferior longitudinal fasciculi. This reduction in fibers associated with the major pathways implicated in visual processing may provide a neuroanatomical basis for the visual dysfunctions observed in these patients.

  19. High GUD Incidence in the Early 20th Century Created a Particularly Permissive Time Window for the Origin and Initial Spread of Epidemic HIV Strains

    PubMed Central

    de Sousa, João Dinis; Müller, Viktor; Lemey, Philippe; Vandamme, Anne-Mieke

    2010-01-01

    The processes that permitted a few SIV strains to emerge epidemically as HIV groups remain elusive. Paradigmatic theories propose factors that may have facilitated adaptation to the human host (e.g., unsafe injections), none of which provide a coherent explanation for the timing, geographical origin, and scarcity of epidemic HIV strains. Our updated molecular clock analyses established relatively narrow time intervals (roughly 1880–1940) for major SIV transfers to humans. Factors that could favor HIV emergence in this time frame may have been genital ulcer disease (GUD), resulting in high HIV-1 transmissibility (4–43%), largely exceeding parenteral transmissibility; lack of male circumcision increasing male HIV infection risk; and gender-skewed city growth increasing sexual promiscuity. We surveyed colonial medical literature reporting incidences of GUD for the relevant regions, concentrating on cities, suffering less reporting biases than rural areas. Coinciding in time with the origin of the major HIV groups, colonial cities showed intense GUD outbreaks with incidences 1.5–2.5 orders of magnitude higher than in mid 20th century. We surveyed ethnographic literature, and concluded that male circumcision frequencies were lower in early 20th century than nowadays, with low rates correlating spatially with the emergence of HIV groups. We developed computer simulations to model the early spread of HIV-1 group M in Kinshasa before, during and after the estimated origin of the virus, using parameters derived from the colonial literature. These confirmed that the early 20th century was particularly permissive for the emergence of HIV by heterosexual transmission. The strongest potential facilitating factor was high GUD levels. Remarkably, the direct effects of city population size and circumcision frequency seemed relatively small. Our results suggest that intense GUD in promiscuous urban communities was the main factor driving HIV emergence. Low circumcision rates

  20. High GUD incidence in the early 20 century created a particularly permissive time window for the origin and initial spread of epidemic HIV strains.

    PubMed

    de Sousa, João Dinis; Müller, Viktor; Lemey, Philippe; Vandamme, Anne-Mieke

    2010-04-01

    The processes that permitted a few SIV strains to emerge epidemically as HIV groups remain elusive. Paradigmatic theories propose factors that may have facilitated adaptation to the human host (e.g., unsafe injections), none of which provide a coherent explanation for the timing, geographical origin, and scarcity of epidemic HIV strains. Our updated molecular clock analyses established relatively narrow time intervals (roughly 1880-1940) for major SIV transfers to humans. Factors that could favor HIV emergence in this time frame may have been genital ulcer disease (GUD), resulting in high HIV-1 transmissibility (4-43%), largely exceeding parenteral transmissibility; lack of male circumcision increasing male HIV infection risk; and gender-skewed city growth increasing sexual promiscuity. We surveyed colonial medical literature reporting incidences of GUD for the relevant regions, concentrating on cities, suffering less reporting biases than rural areas. Coinciding in time with the origin of the major HIV groups, colonial cities showed intense GUD outbreaks with incidences 1.5-2.5 orders of magnitude higher than in mid 20(th) century. We surveyed ethnographic literature, and concluded that male circumcision frequencies were lower in early 20(th) century than nowadays, with low rates correlating spatially with the emergence of HIV groups. We developed computer simulations to model the early spread of HIV-1 group M in Kinshasa before, during and after the estimated origin of the virus, using parameters derived from the colonial literature. These confirmed that the early 20(th) century was particularly permissive for the emergence of HIV by heterosexual transmission. The strongest potential facilitating factor was high GUD levels. Remarkably, the direct effects of city population size and circumcision frequency seemed relatively small. Our results suggest that intense GUD in promiscuous urban communities was the main factor driving HIV emergence. Low circumcision rates

  1. A Large-Scale Distribution of Milk-Based Fortified Spreads: Evidence for a New Approach in Regions with High Burden of Acute Malnutrition

    PubMed Central

    Defourny, Isabelle; Minetti, Andrea; Harczi, Géza; Doyon, Stéphane; Shepherd, Susan; Tectonidis, Milton; Bradol, Jean-Hervé; Golden, Michael

    2009-01-01

    Background There are 146 million underweight children in the developing world, which contribute to up to half of the world's child deaths. In high burden regions for malnutrition, the treatment of individual children is limited by available resources. Here, we evaluate a large-scale distribution of a nutritional supplement on the prevention of wasting. Methods and Findings A new ready-to-use food (RUF) was developed as a diet supplement for children under three. The intervention consisted of six monthly distributions of RUF during the 2007 hunger gap in a district of Maradi region, Niger, for approximately 60,000 children (length: 60–85 cm). At each distribution, all children over 65 cm had their Mid-Upper Arm Circumference (MUAC) recorded. Admission trends for severe wasting (WFH<70% NCHS) in Maradi, 2002–2005 show an increase every year during the hunger gap. In contrast, in 2007, throughout the period of the distribution, the incidence of severe acute malnutrition (MUAC<110 mm) remained at extremely low levels. Comparison of year-over-year admissions to the therapeutic feeding program shows that the 2007 blanket distribution had essentially the same flattening effect on the seasonal rise in admissions as the 2006 individualized treatment of almost 60,000 children moderately wasted. Conclusions These results demonstrate the potential for distribution of fortified spreads to reduce the incidence of severe wasting in large population of children 6–36 months of age. Although further information is needed on the cost-effectiveness of such distributions, these results highlight the importance of re-evaluating current nutritional strategies and international recommendations for high burden areas of childhood malnutrition. PMID:19421316

  2. A large-scale distribution of milk-based fortified spreads: evidence for a new approach in regions with high burden of acute malnutrition.

    PubMed

    Defourny, Isabelle; Minetti, Andrea; Harczi, Géza; Doyon, Stéphane; Shepherd, Susan; Tectonidis, Milton; Bradol, Jean-Hervé; Golden, Michael

    2009-01-01

    There are 146 million underweight children in the developing world, which contribute to up to half of the world's child deaths. In high burden regions for malnutrition, the treatment of individual children is limited by available resources. Here, we evaluate a large-scale distribution of a nutritional supplement on the prevention of wasting. A new ready-to-use food (RUF) was developed as a diet supplement for children under three. The intervention consisted of six monthly distributions of RUF during the 2007 hunger gap in a district of Maradi region, Niger, for approximately 60,000 children (length: 60-85 cm). At each distribution, all children over 65 cm had their Mid-Upper Arm Circumference (MUAC) recorded. Admission trends for severe wasting (WFH<70% NCHS) in Maradi, 2002-2005 show an increase every year during the hunger gap. In contrast, in 2007, throughout the period of the distribution, the incidence of severe acute malnutrition (MUAC<110 mm) remained at extremely low levels. Comparison of year-over-year admissions to the therapeutic feeding program shows that the 2007 blanket distribution had essentially the same flattening effect on the seasonal rise in admissions as the 2006 individualized treatment of almost 60,000 children moderately wasted. These results demonstrate the potential for distribution of fortified spreads to reduce the incidence of severe wasting in large population of children 6-36 months of age. Although further information is needed on the cost-effectiveness of such distributions, these results highlight the importance of re-evaluating current nutritional strategies and international recommendations for high burden areas of childhood malnutrition.

  3. Cortical hot spots and labyrinths: why cortical neuromodulation for episodic migraine with aura should be personalized

    PubMed Central

    Dahlem, Markus A.; Schmidt, Bernd; Bojak, Ingo; Boie, Sebastian; Kneer, Frederike; Hadjikhani, Nouchine; Kurths, Jürgen

    2015-01-01

    Stimulation protocols for medical devices should be rationally designed. For episodic migraine with aura we outline model-based design strategies toward preventive and acute therapies using stereotactic cortical neuromodulation. To this end, we regard a localized spreading depression (SD) wave segment as a central element in migraine pathophysiology. To describe nucleation and propagation features of the SD wave segment, we define the new concepts of cortical hot spots and labyrinths, respectively. In particular, we firstly focus exclusively on curvature-induced dynamical properties by studying a generic reaction-diffusion model of SD on the folded cortical surface. This surface is described with increasing level of details, including finally personalized simulations using patient's magnetic resonance imaging (MRI) scanner readings. At this stage, the only relevant factor that can modulate nucleation and propagation paths is the Gaussian curvature, which has the advantage of being rather readily accessible by MRI. We conclude with discussing further anatomical factors, such as areal, laminar, and cellular heterogeneity, that in addition to and in relation to Gaussian curvature determine the generalized concept of cortical hot spots and labyrinths as target structures for neuromodulation. Our numerical simulations suggest that these target structures are like fingerprints, they are individual features of each migraine sufferer. The goal in the future will be to provide individualized neural tissue simulations. These simulations should predict the clinical data and therefore can also serve as a test bed for exploring stereotactic cortical neuromodulation. PMID:25798103

  4. Cortical hot spots and labyrinths: why cortical neuromodulation for episodic migraine with aura should be personalized.

    PubMed

    Dahlem, Markus A; Schmidt, Bernd; Bojak, Ingo; Boie, Sebastian; Kneer, Frederike; Hadjikhani, Nouchine; Kurths, Jürgen

    2015-01-01

    Stimulation protocols for medical devices should be rationally designed. For episodic migraine with aura we outline model-based design strategies toward preventive and acute therapies using stereotactic cortical neuromodulation. To this end, we regard a localized spreading depression (SD) wave segment as a central element in migraine pathophysiology. To describe nucleation and propagation features of the SD wave segment, we define the new concepts of cortical hot spots and labyrinths, respectively. In particular, we firstly focus exclusively on curvature-induced dynamical properties by studying a generic reaction-diffusion model of SD on the folded cortical surface. This surface is described with increasing level of details, including finally personalized simulations using patient's magnetic resonance imaging (MRI) scanner readings. At this stage, the only relevant factor that can modulate nucleation and propagation paths is the Gaussian curvature, which has the advantage of being rather readily accessible by MRI. We conclude with discussing further anatomical factors, such as areal, laminar, and cellular heterogeneity, that in addition to and in relation to Gaussian curvature determine the generalized concept of cortical hot spots and labyrinths as target structures for neuromodulation. Our numerical simulations suggest that these target structures are like fingerprints, they are individual features of each migraine sufferer. The goal in the future will be to provide individualized neural tissue simulations. These simulations should predict the clinical data and therefore can also serve as a test bed for exploring stereotactic cortical neuromodulation.

  5. Ponticulin is the major high affinity link between the plasma membrane and the cortical actin network in Dictyostelium

    PubMed Central

    1994-01-01

    Interactions between the plasma membrane and underlying actin-based cortex have been implicated in membrane organization and stability, the control of cell shape, and various motile processes. To ascertain the function of high affinity actin-membrane associations, we have disrupted by homologous recombination the gene encoding ponticulin, the major high affinity actin-membrane link in Dictyostelium discoideum amoebae. Cells lacking detectable amounts of ponticulin message and protein also are deficient in high affinity actin-membrane binding by several criteria. First, only 10-13% as much endogenous actin cosediments through sucrose and crude plasma membranes from ponticulin- minus cells, as compared with membranes from the parental strain. Second, purified plasma membranes exhibit little or no binding or nucleation of exogenous actin in vitro. Finally, only 10-30% as much endogenous actin partitions with plasma membranes from ponticulin-minus cells after these cells are mechanically unroofed with polylysine- coated coverslips. The loss of the cell's major actin-binding membrane protein appears to be surprisingly benign under laboratory conditions. Ponticulin-minus cells grow normally in axenic culture and pinocytose FITC-dextran at the same rate as do parental cells. The rate of phagocytosis of particles by ponticulin-minus cells in growth media also is unaffected. By contrast, after initiation of development, cells lacking ponticulin aggregate faster than the parental cells. Subsequent morphogenesis proceeds asynchronously, but viable spores can form. These results indicate that ponticulin is not required for cellular translocation, but apparently plays a role in cell patterning during development. PMID:8089176

  6. Can high-resolution peripheral quantitative computed tomography imaging of subchondral and cortical bone predict condylar fracture in Thoroughbred racehorses?

    PubMed

    Trope, G D; Ghasem-Zadeh, A; Anderson, G A; Mackie, E J; Whitton, R C

    2015-07-01

    High-resolution 3D imaging may improve the prediction and/or early identification of condylar fractures of the distal metacarpus/tarsus and reduce the frequency of breakdown injury in racehorses. To test the hypotheses that horses suffering condylar fractures have higher bone volume fraction (BV/TV) of the distal metacarpal epiphysis, greater subchondral bone thickness at the fracture site and higher second moment of inertia in the metacarpal midshaft as identified with high-resolution 3D imaging. Cross-sectional study using cadaver material. Thoroughbreds that died on racetracks were grouped as: 1) horses with third metacarpal (McIII) fractures with a condylar component (cases, n = 13); 2) horses with no limb fracture (controls, n = 8); 3) horses with fractures in other bones or suspensory apparatus disruption (other fatal injuries, n = 16). The palmar condyles of McIII and the midshaft were examined with high resolution peripheral quantitative computed tomography (HR-pQCT). Statistical analysis included logistic regression and Spearman's correlation. There were no significant differences in BV/TV of distal McIII and second moment of inertia of the midshaft between cases and controls. Epiphyseal bone BV/TV was greater in injured limbs of horses with any fatal limb injury (Groups 1 and 3 combined) compared with controls (odds ratio = 1.20, 95% confidence interval 1.01-1.42, P = 0.034). An epiphyseal BV/TV>0.742 resulted in a sensitivity of 82.8% and specificity of 62.5% in identifying horses with fatal limb injury. In horses without condylar fracture, increased subchondral bone thickness was associated with palmar osteochondral disease lesions in the adjacent condyle (rs = 0.65, P<0.001). Increased BV/TV of the distal metacarpus may have some value for identifying horses at risk of any fatal breakdown injury but not metacarpal condylar fractures. Measurement of parasagittal groove subchondral bone thickness is complicated by adjacent palmar osteochondral disease

  7. Contributions of early cortical processing and reading ability to functional status in individuals at clinical high risk for psychosis.

    PubMed

    Carrión, Ricardo E; Cornblatt, Barbara A; McLaughlin, Danielle; Chang, Jeremy; Auther, Andrea M; Olsen, Ruth H; Javitt, Daniel C

    2015-05-01

    There is a growing recognition that individuals at clinical high risk need intervention for functional impairments, along with emerging psychosis, as the majority of clinical high risk (CHR) individuals show persistent deficits in social and role functioning regardless of transition to psychosis. Recent studies have demonstrated reduced reading ability as a potential cause of functional disability in schizophrenia, related to underlying deficits in generation of mismatch negativity (MMN). The present study extends these findings to subjects at CHR. The sample consisted of 34 CHR individuals and 33 healthy comparison subjects (CNTLs) from the Recognition and Prevention (RAP) Program at the Zucker Hillside Hospital in New York. At baseline, reading measures were collected, along with MMN to pitch, duration, and intensity deviants, and measures of neurocognition, and social and role (academic/work) functioning. CHR subjects showed impairments in reading ability, neurocognition, and MMN generation, relative to CNTLs. Lower-amplitude MMN responses were correlated with worse reading ability, slower processing speed, and poorer social and role functioning. However, when entered into a simultaneous regression, only reduced responses to deviance in sound duration and volume predicted poor social and role functioning, respectively. Deficits in reading ability exist even prior to illness onset in schizophrenia and may represent a decline in performance from prior abilities. As in schizophrenia, deficits are related to impaired MMN generation, suggesting specific contributions of sensory-level impairment to neurocognitive processes related to social and role function. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Contributions of Early Cortical Processing and Reading Ability to Functional Status in Individuals at Clinical High Risk for Psychosis

    PubMed Central

    Carrión, Ricardo E.; Cornblatt, Barbara A.; McLaughlin, Danielle; Chang, Jeremy; Auther, Andrea M.; Olsen, Ruth H.; Javitt, Daniel C.

    2015-01-01

    Background There is a growing recognition that individuals at clinical high risk need intervention for functional impairments, along with emerging psychosis, as the majority of clinical high risk (CHR) individuals show persistent deficits in social and role functioning regardless of transition to psychosis. Recent studies have demonstrated reduced reading ability as a potential cause of functional disability in schizophrenia, related to underlying deficits in generation of mismatch negativity (MMN). The present study extends these findings to subjects at CHR. Methods The sample consisted of 34 CHR individuals and 33 healthy comparisons subjects (CNTLs) from the Recognition and Prevention (RAP) Program at the Zucker Hillside Hospital in New York. At baseline, reading measures were collected, along with MMN to pitch, duration, and intensity deviants, and measures of neurocognition, and social and role (academic/work) functioning. Results CHR subjects showed impairments in reading ability, neurocognition, and MMN generation, relative to CNTLs. Lower-amplitude MMN responses were correlated with worse reading ability, slower processing speed, and poorer social and role functioning. However, when entered into a simultaneous regression, only reduced responses to deviance in sound duration and volume predicted poor social and role functioning, respectively. Conclusions Deficits in reading ability exist even prior to illness onset in schizophrenia and may represent a decline in performance from prior abilities. As in schizophrenia, deficits are related to impaired MMN generation, suggesting specific contributions of sensory-level impairment to neurocognitive processes related to social and role function. PMID:25728833

  9. Cortical thinning in former professional soccer players.

    PubMed

    Koerte, Inga K; Mayinger, Michael; Muehlmann, Marc; Kaufmann, David; Lin, Alexander P; Steffinger, Denise; Fisch, Barbara; Rauchmann, Boris-Stephan; Immler, Stefanie; Karch, Susanne; Heinen, Florian R; Ertl-Wagner, Birgit; Reiser, Maximilian; Stern, Robert A; Zafonte, Ross; Shenton, Martha E

    2016-09-01

    Soccer is the most popular sport in the world. Soccer players are at high risk for repetitive subconcussive head impact when heading the ball. Whether this leads to long-term alterations of the brain's structure associated with cognitive decline remains unknown. The aim of this study was to evaluate cortical thickness in former professional soccer players using high-resolution structural MR imaging. Fifteen former male professional soccer players (mean age 49.3 [SD 5.1] years) underwent high-resolution structural 3 T MR imaging, as well as cognitive testing. Fifteen male, age-matched former professional non-contact sport athletes (mean age 49.6 [SD 6.4] years) served as controls. Group analyses of cortical thickness were performed using voxel-based statistics. Soccer players demonstrated greater cortical thinning with increasing age compared to controls in the right inferolateral-parietal, temporal, and occipital cortex. Cortical thinning was associated with lower cognitive performance as well as with estimated exposure to repetitive subconcussive head impact. Neurocognitive evaluation revealed decreased memory performance in the soccer players compared to controls. The association of cortical thinning and decreased cognitive performance, as well as exposure to repetitive subconcussive head impact, further supports the hypothesis that repetitive subconcussive head impact may play a role in early cognitive decline in soccer players. Future studies are needed to elucidate the time course of changes in cortical thickness as well as their association with impaired cognitive function and possible underlying neurodegenerative process.

  10. Modeling Viral Spread

    PubMed Central

    Graw, Frederik; Perelson, Alan S.

    2016-01-01

    The way in which a viral infection spreads within a host is a complex process that is not well understood. Different viruses, such as human immunodeficiency virus type 1 and hepatitis C virus, have evolved different strategies, including direct cell-to-cell transmission and cell-free transmission, to spread within a host. To what extent these two modes of transmission are exploited in vivo is still unknown. Mathematical modeling has been an essential tool to get a better systematic and quantitative understanding of viral processes that are difficult to discern through strictly experimental approaches. In this review, we discuss recent attempts that combine experimental data and mathematical modeling in order to determine and quantify viral transmission modes. We also discuss the current challenges for a systems-level understanding of viral spread, and we highlight the promises and challenges that novel experimental techniques and data will bring to the field. PMID:27618637

  11. ECoG high gamma activity reveals distinct cortical representations of lyrics passages, harmonic and timbre-related changes in a rock song

    PubMed Central

    Sturm, Irene; Blankertz, Benjamin; Potes, Cristhian; Schalk, Gerwin; Curio, Gabriel

    2014-01-01

    Listening to music moves our minds and moods, stirring interest in its neural underpinnings. A multitude of compositional features drives the appeal of natural music. How such original music, where a composer's opus is not manipulated for experimental purposes, engages a listener's brain has not been studied until recently. Here, we report an in-depth analysis of two electrocorticographic (ECoG) data sets obtained over the left hemisphere in ten patients during presentation of either a rock song or a read-out narrative. First, the time courses of five acoustic features (intensity, presence/absence of vocals with lyrics, spectral centroid, harmonic change, and pulse clarity) were extracted from the audio tracks and found to be correlated with each other to varying degrees. In a second step, we uncovered the specific impact of each musical feature on ECoG high-gamma power (70–170 Hz) by calculating partial correlations to remove the influence of the other four features. In the music condition, the onset and offset of vocal lyrics in ongoing instrumental music was consistently identified within the group as the dominant driver for ECoG high-gamma power changes over temporal auditory areas, while concurrently subject-individual activation spots were identified for sound intensity, timbral, and harmonic features. The distinct cortical activations to vocal speech-related content embedded in instrumental music directly demonstrate that song integrated in instrumental music represents a distinct dimension in complex music. In contrast, in the speech condition, the full sound envelope was reflected in the high gamma response rather than the onset or offset of the vocal lyrics. This demonstrates how the contributions of stimulus features that modulate the brain response differ across the two examples of a full-length natural stimulus, which suggests a context-dependent feature selection in the processing of complex auditory stimuli. PMID:25352799

  12. ECoG high gamma activity reveals distinct cortical representations of lyrics passages, harmonic and timbre-related changes in a rock song.

    PubMed

    Sturm, Irene; Blankertz, Benjamin; Potes, Cristhian; Schalk, Gerwin; Curio, Gabriel

    2014-01-01

    Listening to music moves our minds and moods, stirring interest in its neural underpinnings. A multitude of compositional features drives the appeal of natural music. How such original music, where a composer's opus is not manipulated for experimental purposes, engages a listener's brain has not been studied until recently. Here, we report an in-depth analysis of two electrocorticographic (ECoG) data sets obtained over the left hemisphere in ten patients during presentation of either a rock song or a read-out narrative. First, the time courses of five acoustic features (intensity, presence/absence of vocals with lyrics, spectral centroid, harmonic change, and pulse clarity) were extracted from the audio tracks and found to be correlated with each other to varying degrees. In a second step, we uncovered the specific impact of each musical feature on ECoG high-gamma power (70-170 Hz) by calculating partial correlations to remove the influence of the other four features. In the music condition, the onset and offset of vocal lyrics in ongoing instrumental music was consistently identified within the group as the dominant driver for ECoG high-gamma power changes over temporal auditory areas, while concurrently subject-individual activation spots were identified for sound intensity, timbral, and harmonic features. The distinct cortical activations to vocal speech-related content embedded in instrumental music directly demonstrate that song integrated in instrumental music represents a distinct dimension in complex music. In contrast, in the speech condition, the full sound envelope was reflected in the high gamma response rather than the onset or offset of the vocal lyrics. This demonstrates how the contributions of stimulus features that modulate the brain response differ across the two examples of a full-length natural stimulus, which suggests a context-dependent feature selection in the processing of complex auditory stimuli.

  13. Topography driven spreading.

    PubMed

    McHale, G; Shirtcliffe, N J; Aqil, S; Perry, C C; Newton, M I

    2004-07-16

    Roughening a hydrophobic surface enhances its nonwetting properties into superhydrophobicity. For liquids other than water, roughness can induce a complete rollup of a droplet. However, topographic effects can also enhance partial wetting by a given liquid into complete wetting to create superwetting. In this work, a model system of spreading droplets of a nonvolatile liquid on surfaces having lithographically produced pillars is used to show that superwetting also modifies the dynamics of spreading. The edge speed-dynamic contact angle relation is shown to obey a simple power law, and such power laws are shown to apply to naturally occurring surfaces.

  14. Influence of high dietary sodium intake on the functional subtypes of alpha-adrenoceptors in the renal cortical vasculature of Wistar-Kyoto rats.

    PubMed

    Kazi, R N; Munavvar, A S; Abdullah, N A; Khan, A H; Johns, E J

    2009-01-01

    1 Increased renal vascular resistance is one renal functional abnormality that contributes to hypertension, and alpha(1)-adrenoceptors play a pivotal role in modulating this renal vascular resistance. This study investigates the functional contribution of alpha(1)-adrenoceptor subtypes in the renal cortical vasculature of Wistar-Kyoto rats on a normal sodium diet (WKYNNa) compared with those given saline to drink for 6 weeks (WKYHNa). 2 The renal cortical vascular responses to the adrenergic agonists noradrenaline (NA), methoxamine (ME) and phenylephrine (PE) were measured in WKYHNa and WKYNNa rats either in the absence (the control phase) or presence of chloroethylclonidine (CEC), an alpha(1B)-adrenoceptor antagonist, 5-methylurapidil (5-MeU), an alpha(1A) antagonist, or BMY7378, an alpha(1D) antagonist. 3 Results showed a greater renal cortical vascular sensitivity to NA, PE and ME in the WKYHNa compared with WKYNNa rats (P < 0.05). Moreover, 5-MeU and BMY7378 attenuated adrenergically induced renal cortical vasoconstriction in WKYHNa and WKYNNa rats; this response was largely blunted in CEC-treated WKYHNa rats (all P < 0.05) but not in CEC-treated WKYNNa rats. 4 The data suggest that irrespective of dietary sodium content, in Wistar-Kyoto rats alpha(1A)- and alpha(1D)-subtypes are the major alpha(1)-adrenoceptors in renal cortical vasculature; however, there appears to be a functional involvement of alpha(1B)-adrenoceptors in the WKYHNa rats.

  15. Role of wild birds in the spread of highly pathogenic avian influenza virus H5N1 and implications for global surveillance.

    PubMed

    Feare, Chris J

    2010-03-01

    This paper reviews outbreaks of Asian-lineage highly pathogenic avian influenza virus (HPAIV) H5N1 in wild birds since June 2006, surveillance strategies, and research on virus epidemiology in wild birds to summarize advances in understanding the role of wild birds in the spread of HPAIV H5N1 and the risk that infected wild birds pose for the poultry industry and for public health. Surveillance of apparently healthy wild birds ("active" surveillance) has not provided early warning of likely infection for the poultry industry, whereas searches for and reports of dead birds ("passive" surveillance) have provided evidence of environmental presence of the virus, but not necessarily its source. Most outbreaks in wild birds have occurred during periods when they are experiencing environmental, physiologic, and possibly psychological stress, including adverse winter weather and molt, but not, apparently, long-distance migration. Examination of carcasses of infected birds and experimental challenge with strains of HPAIV H5N1 have provided insight into the course of infection, the extent of virus shedding, and the relative importance of cloacal vs. oropharyngeal excretion. Satellite telemetry of migrating birds is now providing data on the routes taken by individual birds, their speed of migration, and the duration of stopovers. It is still not clear how virus shedding during the apparently clinically silent phase of infection relates to the distance travelled by infected birds. Mounting an immune response and undertaking strenuous exercise associated with long migratory flights may be competitive. This is an area where further research should be directed in order to discover whether wild birds infected with HPAIV H5N1 are able or willing to embark on migration.

  16. Contact line arrest in solidifying spreading drops

    NASA Astrophysics Data System (ADS)

    de Ruiter, Riëlle; Colinet, Pierre; Brunet, Philippe; Snoeijer, Jacco H.; Gelderblom, Hanneke

    2017-04-01

    When does a drop, deposited on a cold substrate, stop spreading? Despite the practical relevance of this question, for example, in airplane icing and three-dimensional metal printing, the detailed mechanism of arrest in solidifying spreading drops has remained debated. Here we consider the spreading and arrest of hexadecane drops of constant volume on two smooth wettable substrates: copper with a high thermal conductivity and glass with a low thermal conductivity. We record the spreading radius and contact angle in time for a range of substrate temperatures. The experiments are complemented by a detailed analysis of the temperature field near the rapidly moving contact line, by means of similarity solutions of the thermohydrodynamic problem. Our combined experimental and theoretical results provide strong evidence that the spreading of solidifying drops is arrested when the liquid at the contact line reaches a critical temperature, which is determined by the effect of kinetic undercooling.

  17. Spreading of a granular droplet

    NASA Astrophysics Data System (ADS)

    Clement, Eric; Sanchez, Ivan; Raynaud, Franck; Lanuza, Jose; Andreotti, Bruno; Aranson, Igor

    2008-03-01

    The influence of controlled vibrations on the granular rheology is investigated in a specifically designed experiment in which a granular film spreads under the action of horizontal vibrations. A nonlinear diffusion equation is derived theoretically that describes the evolution of the deposit shape. A self-similar parabolic shape (the``granular droplet'') and a spreading dynamics are predicted that both agree quantitatively with the experimental results. The theoretical analysis is used to extract effective friction coefficients between the base and the granular layer under sustained and controlled vibrations. A shear thickening regime characteristic of dense granular flows is evidenced at low vibration energy, both for glass beads and natural sand. Conversely, shear thinning is observed at high agitation.

  18. Spreading of a granular droplet

    NASA Astrophysics Data System (ADS)

    Sánchez, Iván; Raynaud, Franck; Lanuza, José; Andreotti, Bruno; Clément, Eric; Aranson, Igor S.

    2007-12-01

    The influence of controlled vibrations on the granular rheology is investigated in a specifically designed experiment in which a granular film spreads under the action of horizontal vibrations. A nonlinear diffusion equation is derived theoretically that describes the evolution of the deposit shape. A self-similar parabolic shape (the“granular droplet”) and a spreading dynamics are predicted that both agree quantitatively with the experimental results. The theoretical analysis is used to extract effective friction coefficients between the base and the granular layer under sustained and controlled vibrations. A shear thickening regime characteristic of dense granular flows is evidenced at low vibration energy, both for glass beads and natural sand. Conversely, shear thinning is observed at high agitation.

  19. Initiation of spreading depression by synaptic and network hyperactivity: Insights into trigger mechanisms of migraine aura.

    PubMed

    Vinogradova, Lyudmila V

    2017-01-01

    Background Cortical spreading depression (SD) is thought to underlie migraine aura but mechanisms of triggering SD in the structurally normal, well-nourished cortex of migraine patients remain unknown. Synaptic and network dysfunctions appear to underlie episodic neurological disorders, including migraine. The narrative review summarizes old and recent experimental evidence for triggering SD by synaptic/network mechanisms and discusses the relevance of the data to migraine pathogenesis. Our hypothesis is that under some conditions synaptic/network hyperactivity may reliably ignite SD, and this mechanism may underlie triggering migraine aura in patients. Findings High-frequency tetanic stimulation of the cortex reliably triggers SD in synaptically connected regions; SD is a reliable cortical response to acute hyperexcitability (epileptic seizures), though chronic epilepsy prevents triggering SD; in the hyperexcitable cortex, SD may be triggered by sensory stimulation; compromised glutamatergic transmission plays the critical role in triggering SD. Conclusion SD may be triggered by dynamic network instability produced by dysfunction of calcium-dependent glutamate release. Synaptic drive from subcortical sensory processing structures (brainstem and/or thalamocortical networks) is able to evoke depolarization of hyperexcitable cortical neurons sufficient to initiate the regenerative SD process. Studying SD initiation by synaptic/network hyperexcitability may provide insights into basic mechanisms underlying SD generation in migraine brain.

  20. A high density of human communication-associated genes in chromosome 7q31-q36: differential expression in human and non-human primate cortices.

    PubMed

    Schneider, E; Jensen, L R; Farcas, R; Kondova, I; Bontrop, R E; Navarro, B; Fuchs, E; Kuss, A W; Haaf, T

    2012-01-01

    The human brain is distinguished by its remarkable size, high energy consumption, and cognitive abilities compared to all other mammals and non-human primates. However, little is known about what has accelerated brain evolution in the human lineage. One possible explanation is that the appearance of advanced communication skills and language has been a driving force of human brain development. The phenotypic adaptations in brain structure and function which occurred on the way to modern humans may be associated with specific molecular signatures in today's human genome and/or transcriptome. Genes that have been linked to language, reading, and/or autism spectrum disorders are prime candidates when searching for genes for human-specific communication abilities. The database and genome-wide expression analyses we present here revealed a clustering of such communication-associated genes (COAG) on human chromosomes X and 7, in particular chromosome 7q31-q36. Compared to the rest of the genome, we found a high number of COAG to be differentially expressed in the cortices of humans and non-human primates (chimpanzee, baboon, and/or marmoset). The role of X-linked genes for the development of human-specific cognitive abilities is well known. We now propose that chromosome 7q31-q36 also represents a hot spot for the evolution of human-specific communication abilities. Selective pressure on the T cell receptor beta locus on chromosome 7q34, which plays a pivotal role in the immune system, could have led to rapid dissemination of positive gene variants in hitchhiking COAG. Copyright © 2012 S. Karger AG, Basel.

  1. Transcranial magnetic stimulation and potential cortical and trigeminothalamic mechanisms in migraine

    PubMed Central

    Andreou, Anna P.; Holland, Philip R.; Akerman, Simon; Summ, Oliver; Fredrick, Joe

    2016-01-01

    A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activity of second order trigemontothalamic and third order thalamocortical neurons in rats. Single pulse transcranial magnetic stimulation significantly inhibited both mechanical and chemically-induced cortical spreading depression when administered immediately post-induction in rats, but not when administered preinduction, and when controlled by a sham stimulation. Additionally transcranial magnetic stimulation significantly inhibited the spontaneous and evoked firing rate of third order thalamocortical projection neurons, but not second order neurons in the trigeminocervical complex, suggesting a potential modulatory effect that may underlie its utility in migraine. In gyrencephalic cat cortices, when administered post-cortical spreading depression, transcranial magnetic stimulation blocked the propagation of cortical spreading depression in two of eight animals. These results are the first to demonstrate that cortical spreading depression can be blocked in vivo using single pulse transcranial magnetic stimulation and further highlight a novel thalamocortical modulatory capacity that may explain the efficacy of magnetic stimulation in the treatment of migraine with and without aura. PMID:27246325

  2. Layer-specific gene expression in epileptogenic type II focal cortical dysplasia: normal-looking neurons reveal the presence of a hidden laminar organization

    PubMed Central

    2014-01-01

    Background Type II focal cortical dysplasias (FCDs) are malformations of cortical development characterised by the disorganisation of the normal neocortical structure and the presence of dysmorphic neurons (DNs) and balloon cells (BCs). The pathogenesis of FCDs has not yet been clearly established, although a number of histopathological patterns and molecular findings suggest that they may be due to abnormal neuronal and glial proliferation and migration processes. In order to gain further insights into cortical layering disruption and investigate the origin of DNs and BCs, we used in situ RNA hybridisation of human surgical specimens with a neuropathologically definite diagnosis of Type IIa/b FCD and a panel of layer-specific genes (LSGs) whose expression covers all cortical layers. We also used anti-phospho-S6 ribosomal protein antibody to investigate mTOR pathway hyperactivation. Results LSGs were expressed in both normal and abnormal cells (BCs and DNs) but their distribution was different. Normal-looking neurons, which were visibly reduced in the core of the lesion, were apparently located in the appropriate cortical laminae thus indicating a partial laminar organisation. On the contrary, DNs and BCs, labelled with anti-phospho-S6 ribosomal protein antibody, were spread throughout the cortex without any apparent rule and showed a highly variable LSG expression pattern. Moreover, LSGs did not reveal any differences between Type IIa and IIb FCD. Conclusion These findings suggest the existence of hidden cortical lamination involving normal-looking neurons, which retain their ability to migrate correctly in the cortex, unlike DNs which, in addition to their morphological abnormalities and mTOR hyperactivation, show an altered migratory pattern. Taken together these data suggest that an external or environmental hit affecting selected precursor cells during the very early stages of cortical development may disrupt normal cortical development. PMID:24735483

  3. Spreading of miscible liquids

    NASA Astrophysics Data System (ADS)

    Walls, Daniel J.; Haward, Simon J.; Shen, Amy Q.; Fuller, Gerald G.

    2016-05-01

    Miscible liquids commonly contact one another in natural and technological situations, often in the proximity of a solid substrate. In the scenario where a drop of one liquid finds itself on a solid surface and immersed within a second, miscible liquid, it will spread spontaneously across the surface. We show experimental findings of the spreading of sessile drops in miscible environments that have distinctly different shape evolution and power-law dynamics from sessile drops that spread in immiscible environments, which have been reported previously. We develop a characteristic time to scale radial data of the spreading sessile drops based on a drainage flow due to gravity. This time scale is effective for a homologous subset of the liquids studied. However, it has limitations when applied to significantly chemically different, yet miscible, liquid pairings; we postulate that the surface energies between each liquid and the solid surface becomes important for this other subset of the liquids studied. Initial experiments performed with pendant drops in miscible environments support the drainage flow observed in the sessile drop systems.

  4. Dynamics of large-scale cortical interactions at high gamma frequencies during word production: Event related causality (ERC) analysis of human electrocorticography (ECoG)

    PubMed Central

    Korzeniewska, Anna; Franaszczuk, Piotr J.; Crainiceanu, Ciprian M.; Kuś, Rafał; Crone, Nathan E.

    2011-01-01

    Intracranial EEG studies in humans have shown that functional brain activation in a variety of functional-anatomic domains of human cortex is associated with an increase in power at a broad range of high gamma (> 60 Hz) frequencies. Although these electrophysiological responses are highly specific for the location and timing of cortical processing and in animal recordings are highly correlated with increased population firing rates, there has been little direct empirical evidence for causal interactions between different recording sites at high gamma frequencies. Such causal interactions are hypothesized to occur during cognitive tasks that activate multiple brain regions. To determine whether such causal interactions occur at high gamma frequencies and to investigate their functional significance, we used event-related causality (ERC) analysis to estimate the dynamics, directionality, and magnitude of event-related causal interactions using subdural electrocorticography (ECoG) recorded during two word production tasks: picture naming and auditory word repetition. A clinical subject who had normal hearing but was skilled in American Signed Language (ASL) provided a unique opportunity to test our hypothesis with reference to a predictable pattern of causal interactions, i.e. that language cortex interacts with different areas of sensorimotor cortex during spoken vs. signed responses. Our ERC analyses confirmed this prediction. During word production with spoken responses, perisylvian language sites had prominent causal interactions with mouth/tongue areas of motor cortex, and when responses were gestured in sign language, the most prominent interactions involved hand and arm areas of motor cortex. Furthermore, we found that the sites from which the most numerous and prominent causal interactions originated, i.e. sites with a pattern of ERC “divergence”, were also sites where high gamma power increases were most prominent and where electrocortical stimulation

  5. Dynamics of large-scale cortical interactions at high gamma frequencies during word production: event related causality (ERC) analysis of human electrocorticography (ECoG).

    PubMed

    Korzeniewska, Anna; Franaszczuk, Piotr J; Crainiceanu, Ciprian M; Kuś, Rafał; Crone, Nathan E

    2011-06-15

    Intracranial EEG studies in humans have shown that functional brain activation in a variety of functional-anatomic domains of human cortex is associated with an increase in power at a broad range of high gamma (>60Hz) frequencies. Although these electrophysiological responses are highly specific for the location and timing of cortical processing and in animal recordings are highly correlated with increased population firing rates, there has been little direct empirical evidence for causal interactions between different recording sites at high gamma frequencies. Such causal interactions are hypothesized to occur during cognitive tasks that activate multiple brain regions. To determine whether such causal interactions occur at high gamma frequencies and to investigate their functional significance, we used event-related causality (ERC) analysis to estimate the dynamics, directionality, and magnitude of event-related causal interactions using subdural electrocorticography (ECoG) recorded during two word production tasks: picture naming and auditory word repetition. A clinical subject who had normal hearing but was skilled in American Signed Language (ASL) provided a unique opportunity to test our hypothesis with reference to a predictable pattern of causal interactions, i.e. that language cortex interacts with different areas of sensorimotor cortex during spoken vs. signed responses. Our ERC analyses confirmed this prediction. During word production with spoken responses, perisylvian language sites had prominent causal interactions with mouth/tongue areas of motor cortex, and when responses were gestured in sign language, the most prominent interactions involved hand and arm areas of motor cortex. Furthermore, we found that the sites from which the most numerous and prominent causal interactions originated, i.e. sites with a pattern of ERC "divergence", were also sites where high gamma power increases were most prominent and where electrocortical stimulation mapping

  6. Focal Peak Activities in Spread of Interictal-Ictal Discharges in Epilepsy with Beamformer MEG: Evidence for an Epileptic Network?

    PubMed Central

    Rose, Douglas F.; Fujiwara, Hisako; Holland-Bouley, Katherine; Greiner, Hansel M.; Arthur, Todd; Mangano, Francesco T.

    2013-01-01

    Non-invasive studies to predict regions of seizure onset are important for planning intracranial grid locations for invasive cortical recordings prior to resective surgery for patients with medically intractable epilepsy. The neurosurgeon needs to know both the seizure onset zone (SOZ) and the region of immediate cortical spread to determine the epileptogenic zone to be resected. The immediate zone of spread may be immediately adjacent, on a nearby gyrus, in a different lobe, and sometimes even in the contralateral cerebral hemisphere. We reviewed consecutive simultaneous EEG/MEG recordings on 162 children with medically intractable epilepsy. We analyzed the MEG signals in the bandwidth 20–70 Hz with a beamformer algorithm, synthetic aperture magnetometry, at a 2.5 mm voxel spacing throughout the brain (virtual sensor locations, VSLs) with the kurtosis statistic (g2) to determine presence of excess kurtosis (γ2) consistent with intermittent increased high frequency spikiness of the background. The MEG time series was reconstructed (virtual sensor signals) at each of these VSLs. The VS signals were further examined with a relative peak amplitude spike detection algorithm. The time of VS spike detection was compared to the simultaneous EEG and MEG sensor signals for presence of conventional epileptiform spike morphology in the latter signals. The time of VS spike detection was compared across VSLs to determine earliest and last VSL to show a VS spike. Seven subjects showed delay in activation across VS locations detectable on visual examination. We compared the VS locations that showed earliest and later VS spikes with the locations on intracranial grid locations by electrocorticography (ECoG) that showed spikes and both onset and spread of seizures. We compared completeness of resection of VS locations to postoperative outcome. The VS locations for spike onset and spread were similar to locations for ictal onset and spread by ECoG. PMID:23675367

  7. Mechanisms of Hierarchical Cortical Maturation

    PubMed Central

    Chomiak, Taylor; Hu, Bin

    2017-01-01

    Cortical information processing is structurally and functionally organized into hierarchical pathways, with primary sensory cortical regions providing modality specific information and associative cortical regions playing a more integrative role. Historically, there has been debate as to whether primary cortical regions mature earlier than associative cortical regions, or whether both primary and associative cortical regions mature simultaneously. Identifying whether primary and associative cortical regions mature hierarchically or simultaneously will not only deepen our understanding of the mechanisms that regulate brain maturation, but it will also provide fundamental insight into aspects of adolescent behavior, learning, neurodevelopmental disorders and computational models of neural processing. This mini-review article summarizes the current evidence supporting the sequential and hierarchical nature of cortical maturation, and then proposes a new cellular model underlying this process. Finally, unresolved issues associated with hierarchical cortical maturation are also addressed. PMID:28959187

  8. Alterations of lateral temporal cortical gray matter and facial memory as vulnerability indicators for schizophrenia: an MRI study in youth at familial high-risk for schizophrenia

    PubMed Central

    Brent, Benjamin K.; Rosso, Isabelle M.; Thermenos, Heidi W.; Holt, Daphne J.; Faraone, Stephen V.; Makris, Nikos; Tsuang, Ming T.; Seidman, Larry J.

    2015-01-01

    Background Structural alterations of the lateral temporal cortex (LTC) in association with memory impairments have been reported in schizophrenia. This study investigated whether alterations of LTC structure were linked with impaired facial and/or verbal memory in young first-degree relatives of people with schizophrenia and, thus, may be indicators of vulnerability to the illness. Methods Subjects included 27 non-psychotic, first-degree relatives of schizophrenia patients, and 48 healthy controls, between the ages of 13 and 28. Participants underwent high-resolution magnetic resonance imaging (MRI) at 1.5 Tesla. The LTC was parcellated into superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, and temporal pole. Total cerebral and LTC volumes were measured using semi-automated morphometry. The Wechsler Memory Scale – Third Edition and the Children’s Memory Scale – Third Edition assessed facial and verbal memory. General linear models tested for associations among LTC subregion volumes, familial risk and memory. Results Compared with controls, relatives had significantly smaller bilateral middle temporal gyri. Moreover, right middle temporal gyral volume showed a significant positive association with delayed facial memory in relatives. Conclusion These results support the hypothesis that smaller middle temporal gyri are related to the genetic liability to schizophrenia and may be linked with reduced facial memory in persons at genetic risk for the illness. The findings add to the growing evidence that children at risk for schizophrenia on the basis of positive family history have cortical and subcortical structural brain abnormalities well before psychotic illness occurs. PMID:26621001

  9. Low and then high frequency oscillations of distinct right cortical networks are progressively enhanced by medium and long term Satyananda Yoga meditation practice

    PubMed Central

    Thomas, John; Jamieson, Graham; Cohen, Marc

    2014-01-01

    Meditation proficiency is related to trait-like (learned) effects on brain function, developed over time. Previous studies show increases in EEG power in lower frequency bands (theta, alpha) in experienced meditators in both meditation states and baseline conditions. Higher gamma band power has been found in advanced Buddhist meditators, yet it is not known if this occurs in Yoga meditation practices. This study used eLORETA to compare differences in cortical source activity underlying scalp EEG from intermediate (mean experience 4 years) and advanced (mean experience 30 years) Australian meditators from the Satyananda Yoga tradition during a body-steadiness meditation, mantra meditation, and non-meditation mental calculation condition. Intermediate Yoga meditators showed greater source activity in low frequencies (particularly theta and alpha1) during mental calculation, body-steadiness and mantra meditation. A similar spatial pattern of significant differences was found in all conditions but the number of significant voxels was double during body-steadiness and mantra meditation than in the non-meditation (calculation) condition. These differences were greatest in right (R) superior frontal and R precentral gyri and extended back to include the R parietal and occipital lobes. Advanced Yoga meditators showed greater activity in high frequencies (beta and especially gamma) in all conditions but greatly expanded during meditation practice. Across all conditions (meditation and non-meditation) differences were greatest in the same regions: R insul