Sample records for peak brain development
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Metabolic costs and evolutionary implications of human brain development.
Kuzawa, Christopher W; Chugani, Harry T; Grossman, Lawrence I; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R; Wildman, Derek E; Sherwood, Chet C; Leonard, William R; Lange, Nicholas
2014-09-09
The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain's glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain-body metabolic trade-offs using the ratios of brain glucose uptake to the body's resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate.
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Metabolic costs and evolutionary implications of human brain development
Kuzawa, Christopher W.; Chugani, Harry T.; Grossman, Lawrence I.; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R.; Wildman, Derek E.; Sherwood, Chet C.; Leonard, William R.; Lange, Nicholas
2014-01-01
The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain’s glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain–body metabolic trade-offs using the ratios of brain glucose uptake to the body’s resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate. PMID:25157149
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Fetal functional imaging portrays heterogeneous development of emerging human brain networks
Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M.; Prayer, Daniela; Schöpf, Veronika; Langs, Georg
2014-01-01
The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26–29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity. PMID:25374531
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Fetal functional imaging portrays heterogeneous development of emerging human brain networks.
Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M; Prayer, Daniela; Schöpf, Veronika; Langs, Georg
2014-01-01
The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26-29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity.
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Transcranial Photoacoustic Measurements of Cold-Injured Brains in Rats
NASA Astrophysics Data System (ADS)
Ueda, Yoshinori; Sato, Shunichi; Hasegawa, Makoto; Nawashiro, Hiroshi; Saitoh, Daizoh; Shima, Katsuji; Ashida, Hiroshi; Obara, Minoru
2005-09-01
We performed transcranial photoacoustic measurements of cold-injured brains in rats. Before inducing injury, a signal peak was observed at two locations corresponding to the surfaces of the skull and brain, while after injury, a third peak appeared at a location corresponding to the back surface of the skull; the third peak was found to be caused by subdural hematoma. The signal peak for the brain surface shifted to a deeper region with elapse of time after injury, indicating deformation of the brain. These findings suggest that small hemorrhage and morphological change of the brain can be transcranially detected by photoacoustic measurement.
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Onoda, Atsuto; Kawasaki, Takayasu; Tsukiyama, Koichi; Takeda, Ken; Umezawa, Masakazu
2017-01-01
Environmental stimulation during brain development is an important risk factor for the development of neurodegenerative disease. Clinical evidence indicates that prenatal exposure to particulate air pollutants leads to diffuse damage to the neurovascular unit in the developing brain and accelerates neurodegeneration. Maternal exposure to carbon black nanoparticles (CB-NPs), used as a model for particulate air pollution, induces long-lasting diffuse perivascular abnormalities. We aimed to comprehensively characterize the perivascular abnormalities related to maternal NPs exposure using Fourier transform infrared microspectroscopy ( in situ FT-IR) and classical staining analysis. Pregnant ICR mice were intranasally treated with a CB-NPs suspension (95 μg/kg at a time) on gestational days 5 and 9. Brains were collected 6 weeks after birth and sliced to prepare 10-μm-thick serial sections. Reflective spectra of in situ FT-IR were acquired using lattice measurements ( x -axis: 7, y -axis: 7, 30-μm apertures) around a centered blood vessel. We also performed mapping analysis of protein secondary structures. Serial sections were stained with using periodic acid-Schiff or immunofluorescence to examine the phenotypes of the perivascular areas. Peaks of amide I bands in spectra from perivascular areas were shifted by maternal NPs exposure. However, there were two types of peak-shift in one mouse in the exposure group. Some vessels had a large peak-shift and others had a small peak-shift. In situ FT-IR combined with traditional staining revealed that the large peak-shift was induced around blood vessel adjacent to astrocytes with glial fibrillary acidic protein and aquaporin-4 over-expression and perivascular macrophages (PVMs) with enlarged lysosome granules. Furthermore, protein secondary structural analysis indicated that maternal NPs exposure led to increases in β-sheet content and decreases in α-helix content in areas that are mostly close to the centered blood vessel displaying histopathological changes. These results suggest that β-sheet-rich waste proteins, which are denatured by maternal NPs exposure, likely accumulate in the perivascular space as they are processed by the clearance systems in the brain. This may in turn lead the denaturation of PVMs and astrocyte activation. The risk of neurodegeneration may be enhanced by exposure to particulate air pollutants during brain development following the perivascular accumulation of β-sheet-rich waste proteins.
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NMR imaging and spectroscopy of the mammalian central nervous system after heavy ion radiation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Richards, T.
NMR imaging, NMR spectroscopic, and histopathologic techniques were used to study the proton relaxation time and related biochemical changes in the central nervous system after helium beam in vivo irradiation of the rodent brain. The spectroscopic observations reported in this dissertation were made possible by development of methods for measuring the NMR parameters of the rodent brain in vivo and in vitro. The methods include (1) depth selective spectroscopy using an optimization of rf pulse energy based on a priori knowledge of N-acetyl aspartate and lipid spectra of the normal brain, (2) phase-encoded proton spectroscopy of the living rodent usingmore » a surface coil, and (3) dual aqueous and organic tissue extraction technique for spectroscopy. Radiation induced increases were observed in lipid and p-choline peaks of the proton spectrum, in vivo. Proton NMR spectroscopy measurements on brain extracts (aqueous and organic solvents) were made to observe chemical changes that could not be seen in vivo. Radiation-induced changes were observed in lactate, GABA, glutamate, and p-choline peak areas of the aqueous fraction spectra. In the organic fraction, decreases were observed in peak area ratios of the terminal-methyl peaks, the N-methyl groups of choline, and at a peak at 2.84 ppM (phosphatidyl ethanolamine and phosphatidyl serine resonances) relative to TMS. With histology and Evans blue injections, blood-brain barrier alternations were seen as early as 4 days after irradiation. 83 references, 53 figures.« less
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Tanaka, Chiaki; Matsui, Mie; Uematsu, Akiko; Noguchi, Kyo; Miyawaki, Toshio
2012-01-01
Brain development during early life in healthy individuals is rapid and dynamic, indicating that this period plays a very important role in neural and functional development. The frontal and temporal lobes are known to play a particularly important role in cognition. The study of healthy frontal and temporal lobe development in children is therefore of considerable importance. A better understanding of how these brain regions develop could also aid in the diagnosis and treatment of neurodevelopmental disorders. Some developmental studies have used magnetic resonance imaging (MRI) to examine infant brains, but it remains the case that relatively little is known about cortical brain development in the first few years of life. In the present study we examined whole brain, temporal lobe and frontal lobe developmental trajectories from infancy to early adulthood in healthy individuals, considering gender and brain hemisphere differences. We performed a cross-sectional, longitudinal morphometric MRI study of 114 healthy individuals (54 females and 60 males) aged 1 month to 25 years old (mean age ± SD 8.8 ± 6.9). We measured whole brain, temporal and frontal lobe gray matter (GM)/white matter (WM) volumes, following previously used protocols. There were significant non-linear age-related volume changes in all regions. Peak ages of whole brain, temporal lobe and frontal lobe development occurred around pre-adolescence (9-12 years old). GM volumes for all regions increased significantly as a function of age. Peak age was nevertheless lobe specific, with a pattern of earlier peak ages for females in both temporal and frontal lobes. Growth change in whole brain GM volume was larger in males than in females. However, GM volume growth changes for the temporal and frontal lobes showed a somewhat different pattern. GM volume for both temporal and frontal lobes showed a greater increase in females until around 5-6 years old, at which point this tendency reversed (GM volume changes in males became greater), with male GM volume increasing for a longer time than that of females. WM volume growth changes were similar across regions, all increasing rapidly until early childhood but slowing down thereafter. All regions displayed significant rightward volumetric asymmetry regardless of sex. Furthermore, the right temporal and frontal lobes showed a greater volumetric increase than the left for the first several years, with this tendency reversing at around 6 years of age. In addition, the left frontal and temporal lobes increased in volume for a longer period of time. Taken together, these findings indicated that brain developmental trajectories differ depending on brain region, sex and brain hemisphere. Gender-related factors such as sex hormones and functional laterality may affect brain development. Copyright © 2012 S. Karger AG, Basel.
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Shapira, Niva
2009-01-01
Though eggs have the unique capacity, like breastmilk, to concentrate essential nutrients required for early growth and brain development of offspring - i.e. n-3 PUFA, increasingly deficient and sources contaminated - cholesterol and allergy concerns often exclude them from perinatal recommendations. Egg's potential contribution of key nutrients required for peak brain development are re-evaluated vis-à-vis fortification, accessibility, and risks. Contributions of standard (USDA) and fortified (selected market-available) egg compositions to perinatal requirements for critical brain-supporting nutrients were compared to human and cow milks, and risks and recommendations evaluated. Standard egg has already higher concentrations/kcal of iron, selenium, zinc, choline, vitamins B12 and E, and essential amino acids (plus taurine) than human milk. Fortified egg could further yield significant n-3 PUFA % recommendations for pregnancy-lactation (total n-3 69.6-75.0% [DRI=1400-1300 mg/day]), including DHA (120.1-129.3%, mostly approximately 80% [calculated DRI=140-130 mg/day]), plus antioxidant vitamins A (9.0-15.2%) and E (51.6-65.3%), and minerals iodine (33.6-44.5%) and selenium (33.7-39.3%); % recommendations for children (1-3 y) even more. Cholesterol, important for nerve membranes and learning, may not be generally contraindicated in childbearing-aged women (approximately 10.5% hypercholesterolemia), and early-life egg exposure may increase tolerance. Egg-inclusive perinatal nutrition programs have shown significant contributions. Eggs, especially target-fortified, may provide a unique nutritional supplement for peak brain development continously during pregnancy, nursing, and infancy (from 6 months), especially vs. insufficiencies. Missing nutritional opportunities by egg exclusion vs. concerns of hypercholesterolemia or allergy could be addressed individually, rather than as general recommendations, warranting further research and targeted egg design.
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Murad, S; Strycharz, G D; Kishimoto, Y
1976-09-10
Rat brain postnuclear preparations catalyzed the alpha-hydroxylation of nervonic acid with an apparent Km of 3 muM. Evidence has been presented which suggests that nervonic acid in the brain is hydroxylated by the same enzyme system which hydroxylates lignoceric acid. The hydroxylase activity in brains of normal (euthyroid) rats increased rapidly from a low in the period immediately following birth to a maximum at the 23rd day and then declined to a low level characteristic of the mature brain. Neonatal hypothyroidism retarded the development of the activity and shifted its peak to the 39th day after birth. Conversely, neonatal hyperthyroidism accelerated the entire developmental pattern and shifted the peak to the 16th day after birth. The hydroxylase activity in mouse brain was also increased by thyroid hormone administration from the 13th through the 18th day after birth. Unlike normal mice, the low activity in jimpy mice was not affected by this treatment. It is concluded that thyroid hormones play an important role in the control of brain fatty acid alpha-hydroxylation. The stimulation of alpha-hydroxy fatty acid synthesis in response to hyperthyroidism during the early postnatal period may be one of the major effects of thyroid hormones in accelerating myelination of the central nervous system.
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Age-related apparent diffusion coefficient changes in the normal brain.
Watanabe, Memi; Sakai, Osamu; Ozonoff, Al; Kussman, Steven; Jara, Hernán
2013-02-01
To measure the mean diffusional age-related changes of the brain over the full human life span by using diffusion-weighted spin-echo single-shot echo-planar magnetic resonance (MR) imaging and sequential whole-brain apparent diffusion coefficient (ADC) histogram analysis and, secondarily, to build mathematical models of these normal age-related changes throughout human life. After obtaining institutional review board approval, a HIPAA-compliant retrospective search was conducted for brain MR imaging studies performed in 2007 for various clinical indications. Informed consent was waived. The brain data of 414 healthy subjects (189 males and 225 females; mean age, 33.7 years; age range, 2 days to 89.3 years) were obtained with diffusion-weighted spin-echo single-shot echo-planar MR imaging. ADC histograms of the whole brain were generated. ADC peak values, histogram widths, and intracranial volumes were plotted against age, and model parameters were estimated by using nonlinear regression. Four different stages were identified for aging changes in ADC peak values, as characterized by specific mathematical terms: There were age-associated exponential decays for the maturation period and the development period, a constant term for adulthood, and a linear increase for the senescence period. The age dependency of ADC peak value was simulated by using four-term six-coefficient function, including biexponential and linear terms. This model fit the data very closely (R(2) = 0.91). Brain diffusivity as a whole demonstrated age-related changes through four distinct periods of life. These results could contribute to establishing an ADC baseline of the normal brain, covering the full human life span.
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Maturation of the auditory t-complex brain response across adolescence.
Mahajan, Yatin; McArthur, Genevieve
2013-02-01
Adolescence is a time of great change in the brain in terms of structure and function. It is possible to track the development of neural function across adolescence using auditory event-related potentials (ERPs). This study tested if the brain's functional processing of sound changed across adolescence. We measured passive auditory t-complex peaks to pure tones and consonant-vowel (CV) syllables in 90 children and adolescents aged 10-18 years, as well as 10 adults. Across adolescence, Na amplitude increased to tones and speech at the right, but not left, temporal site. Ta amplitude decreased at the right temporal site for tones, and at both sites for speech. The Tb remained constant at both sites. The Na and Ta appeared to mature later in the right than left hemisphere. The t-complex peaks Na and Tb exhibited left lateralization and Ta showed right lateralization. Thus, the functional processing of sound continued to develop across adolescence and into adulthood. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.
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Neuroscience imaging enabled by new highly tunable and high peak power femtosecond lasers
NASA Astrophysics Data System (ADS)
Hakulinen, T.; Klein, J.
2017-02-01
Neuroscience applications benefit from recent developments in industrial femtosecond laser technology. New laser sources provide several megawatts of peak power at wavelength of 1040 nm, which enables simultaneous optogenetics photoactivation of tens or even hundreds of neurons using red shifted opsins. Another recent imaging trend is to move towards longer wavelengths, which would enable access to deeper layers of tissue due to lower scattering and lower absorption in the tissue. Femtosecond lasers pumping a non-collinear optical parametric amplifier (NOPA) enable the access to longer wavelengths with high peak powers. High peak powers of >10 MW at 1300 nm and 1700 nm allow effective 3-photon excitation of green and red shifted calcium indicators respectively and access to deeper, sub-cortex layers of the brain. Early results include in vivo detection of spontaneous activity in hippocampus within an intact mouse brain, where neurons express GCaMP6 activated in a 3-photon process at 1320 nm.
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NASA Technical Reports Server (NTRS)
Hoffman, L. F.; Horowitz, J. M.
1984-01-01
The effect of decreasing of brain temperature on the brainstem auditory evoked response (BAER) in rats was investigated. Voltage pulses, applied to a piezoelectric crystal attached to the skull, were used to evoke stimuli in the auditory system by means of bone-conducted vibrations. The responses were recorded at 37 C and 34 C brain temperatures. The peaks of the BAER recorded at 34 C were delayed in comparison with the peaks from the 37 C wave, and the later peaks were more delayed than the earlier peaks. These results indicate that an increase in the interpeak latency occurs as the brain temperature is decreased. Preliminary experiments, in which responses to brief angular acceleration were used to measure the brainstem vestibular evoked response (BVER), have also indicated increases in the interpeak latency in response to the lowering of brain temperature.
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Changes in Lipidome Composition during Brain Development in Humans, Chimpanzees, and Macaque Monkeys
Li, Qian; Bozek, Katarzyna; Xu, Chuan; Guo, Yanan; Sun, Jing; Pääbo, Svante; Sherwood, Chet C.; Hof, Patrick R.; Ely, John J.; Li, Yan; Willmitzer, Lothar
2017-01-01
Lipids are essential components of the brain. Here, we conducted a comprehensive mass spectrometry-based analysis of lipidome composition in the prefrontal cortex of 40 humans, 40 chimpanzees, and 40 rhesus monkeys over postnatal development and adulthood. Of the 11,772 quantified lipid peaks, 7,589 change significantly along the lifespan. More than 60% of these changes occur prior to adulthood, with less than a quarter associated with myelination progression. Evolutionarily, 36% of the age-dependent lipids exhibit concentration profiles distinct to one of the three species; 488 (18%) of them were unique to humans. In both humans and chimpanzees, the greatest extent of species-specific differences occurs in early development. Human-specific lipidome differences, however, persist over most of the lifespan and reach their peak from 20 to 35 years of age, when compared with chimpanzee-specific ones. PMID:28158622
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Manchado de Sola, Francisco; Vilches, Manuel; Prezado, Yolanda; Lallena, Antonio M
2018-05-15
The purpose of this study was to assess the effects of brain movements induced by heartbeat on dose distributions in synchrotron micro- and minibeam radiation therapy and to develop a model to help guide decisions and planning for future clinical trials. The Monte Carlo code PENELOPE was used to simulate the irradiation of a human head phantom with a variety of micro- and minibeam arrays, with beams narrower than 100 μm and above 500 μm, respectively, and with radiation fields of 1 × 2 cm and 2 × 2 cm. The dose in the phantom due to these beams was calculated by superposing the dose profiles obtained for a single beam of 1 μm × 2 cm. A parameter δ, accounting for the total displacement of the brain during the irradiation and due to the cardiosynchronous pulsation, was used to quantify the impact on peak-to-valley dose ratios and the full width at half maximum. The difference between the maximum (at the phantom entrance) and the minimum (at the phantom exit) values of the peak-to-valley dose ratio reduces when the parameter δ increases. The full width at half maximum remains almost constant with depth for any δ value. Sudden changes in the two quantities are observed at the interfaces between the various tissues (brain, skull, and skin) present in the head phantom. The peak-to-valley dose ratio at the center of the head phantom reduces when δ increases, remaining above 70% of the static value only for minibeams and δ smaller than ∼200 μm. Optimal setups for brain treatments with synchrotron radiation micro- and minibeam combs depend on the brain displacement due to cardiosynchronous pulsation. Peak-to-valley dose ratios larger than 90% of the maximum values obtained in the static case occur only for minibeams and relatively large dose rates. © 2018 American Association of Physicists in Medicine.
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NASA Astrophysics Data System (ADS)
Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.
2016-03-01
In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.
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Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami
2018-05-01
Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.
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Robinson, Matthew M; Lowe, Val J; Nair, K Sreekumaran
2018-01-01
Aerobic exercise training can increase brain volume and blood flow, but the impact on brain metabolism is less known. We determined whether high-intensity interval training (HIIT) increases brain metabolism by measuring brain glucose uptake in younger and older adults. Brain glucose uptake was measured before and after HIIT or a sedentary (SED) control period within a larger exercise study. Study procedures were performed at the Mayo Clinic in Rochester, MN. Participants were younger (18 to 30 years) or older (65 to 80 years) SED adults who were free of major medical conditions. Group sizes were 15 for HIIT (nine younger and six older) and 12 for SED (six younger and six older). Participants completed 12 weeks of HIIT or SED. HIIT was 3 days per week of 4 × 4 minute intervals at over 90% of peak aerobic capacity (VO2peak) with 2 days per week of treadmill walking at 70% VO2peak. Resting brain glucose uptake was measured using 18F-fluorodeoxyglucose positron emission tomography scans at baseline and at week 12. Scans were performed at 96 hours after exercise. VO2peak was measured by indirect calorimetry. Glucose uptake increased significantly in the parietal-temporal and caudate regions after HIIT compared with SED. The gains with HIIT were not observed in all brain regions. VO2peak was increased for all participants after HIIT and did not change with SED. We demonstrate that brain glucose metabolism increased after 12 weeks of HIIT in adults in regions where it is reduced in Alzheimer's disease. Copyright © 2017 Endocrine Society
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Maksimova, M Yu; Sermagambetova, Zh N; Skrylev, S I; Fedin, P A; Koshcheev, A Yu; Shchipakin, V L; Sinicyn, I A
To assess brain stem dysfunction in patients with hemodynamically significant stenosis of vertebral arteries (VA) using short latency brainstem auditory evoked potentials (BAEP). The study group included 50 patients (mean age 64±6 years) with hemodynamically significant extracranial VA stenosis. Patients with hemodynamically significant extracranial VA stenosis had BAEP abnormalities including the elongation of interpeak intervals I-V and peak V latency as well as the reduction of peak I amplitude. After transluminal balloon angioplasty with stenting of VA stenoses, there was a shortening of peak V latency compared to the preoperative period that reflected the improvement of brain stem conductive functions. Atherostenosis of vertebral arteries is characterized by the signs of brain stem dysfunction, predominantly in the pontomesencephal brain stem. After transluminal balloon angioplasty with stenting of VA, the improvement of brain stem conductive functions was observed.
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Leithead, Joanna A; Armstrong, Matthew J; Corbett, Christopher; Andrew, Mark; Kothari, Chirag; Gunson, Bridget K; Muiesan, Paolo; Ferguson, James W
2013-11-01
Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury (AKI). This suggests that hepatic ischemia-reperfusion injury may play a critical role in the pathogenesis of AKI after liver transplantation. The aim of this single-center study was to determine if hepatic ischemia-reperfusion injury, estimated by peak peri-operative serum amino-transferase (AST), is associated with AKI following donation after brain death (DBD) liver transplantation. A total of 296 patients received 298 DBD liver transplants from January 2007 to June 2011. The incidence of AKI was 35.9%. AKI was a risk factor for chronic kidney disease (P = 0.037) and mortality (P = 0.002). On univariate analysis, peak AST correlated with peak creatinine (P < 0.001) and peak change in creatinine from baseline (P < 0.001). Peak AST was higher in AKI patients (P < 0.001). The incidence of AKI in patients with a peak AST of <1500, 1500-2999 and ≥ 3000 U/l was 26.1%, 39.8% and 71.2%, respectively (P < 0.001). On multiple logistic regression analysis, peak AST was independently associated with the development of AKI (P < 0.001). In conclusion, hepatic ischemia-reperfusion injury demonstrates a strong relationship with peri-operative AKI in DBD liver transplant recipients. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.
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Ullner, Paivi M; Di Nardo, Alessia; Goldman, James E; Schobel, Scott; Yang, Hong; Engelstad, Kristin; Wang, Dong; Sahin, Mustafa; De Vivo, Darryl C
2009-10-01
Glucose transporter type 1 (Glut-1) facilitates glucose flux across the blood-brain-barrier. In humans, Glut-1 deficiency causes acquired microcephaly, seizures and ataxia, which are recapitulated in our Glut-1 haploinsufficient mouse model. Postnatal brain weight deceleration and development of reactive astrogliosis were significant by P21 in Glut-1(+/-) mice. The brain weight differences remained constant after P21 whereas the reactive astrocytosis continued to increase and peaked at P90. Brain immunoblots showed increased phospho-mTOR and decreased phospho-GSK3-beta by P14. After fasting, the mature Glut-1(+/-) females showed a trend towards elevated phospho-GSK3-beta, a possible neuroprotective response. Lithium chloride treatment of human skin fibroblasts from control and Glut-1 DS patients produced a 45% increase in glucose uptake. Brain imaging of mature Glut-1(+/-) mice revealed a significantly decreased hippocampal volume. These subtle immunochemical changes reflect chronic nutrient deficiency during brain development and represent the experimental correlates to the human neurological phenotype associated with Glut-1 DS.
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Ahn, So Yoon; Yoo, Hye Soo; Lee, Jang Hoon; Sung, Dong Kyung; Jung, Yu Jin; Sung, Se In; Lim, Keun Ho; Chang, Yun Sil; Lee, Jung Hee; Kim, Ki Soo; Park, Won Soon
2013-07-01
This study was performed to determine the accuracy of proton magnetic spectroscopy ((1)H-MRS) lipid peak as a noninvasive tool for quantitative in vivo detection of brain cell death. Seven day-old Sprague Dawley rats were subjected to 8% oxygen following a unilateral carotid artery ligation. For treatment, cycloheximide was given immediately after hypoxic ischemia (HI). Lipid peak was measured using (1)H-MRS at 24 hr after HI, and then brains were harvested for fluorocytometric analyses with annexin V/propidium iodide (PI) and fluorescent probe JC-1, and for adenosine-5'-triphosphate (ATP) and lactate. Increased lipid peak at 1.3 ppm measured with (1)H-MRS, apoptotic and necrotic cells, and loss of mitochondrial membrane potential (ΔΨ) at 24 hr after HI were significantly improved with cycloheximide treatment. Significantly reduced brain ATP and increased lactate levels observed at 24 hr after HI showed a tendency to improve without statistical significance with cycloheximide treatment. Lipid peak at 1.3 ppm showed significant positive correlation with both apoptotic and necrotic cells and loss of ΔΨ, and negative correlation with normal live cells. Lipid peak at 1.3 ppm measured by (1)H-MRS might be a sensitive and reliable diagnostic tool for quantitative in vivo detection of brain cell death after HI.
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Chen, Zhaoxue; Yu, Haizhong; Chen, Hao
2013-12-01
To solve the problem of traditional K-means clustering in which initial clustering centers are selected randomly, we proposed a new K-means segmentation algorithm based on robustly selecting 'peaks' standing for White Matter, Gray Matter and Cerebrospinal Fluid in multi-peaks gray histogram of MRI brain image. The new algorithm takes gray value of selected histogram 'peaks' as the initial K-means clustering center and can segment the MRI brain image into three parts of tissue more effectively, accurately, steadily and successfully. Massive experiments have proved that the proposed algorithm can overcome many shortcomings caused by traditional K-means clustering method such as low efficiency, veracity, robustness and time consuming. The histogram 'peak' selecting idea of the proposed segmentootion method is of more universal availability.
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Iqbal, Zohaib; Wilson, Neil E; Thomas, M Albert
2016-03-01
Several different pathologies, including many neurodegenerative disorders, affect the energy metabolism of the brain. Glutamate, a neurotransmitter in the brain, can be used as a biomarker to monitor these metabolic processes. One method that is capable of quantifying glutamate concentration reliably in several regions of the brain is TE-averaged (1) H spectroscopic imaging. However, this type of method requires the acquisition of multiple TE lines, resulting in long scan durations. The goal of this experiment was to use non-uniform sampling, compressed sensing reconstruction and an echo planar readout gradient to reduce the scan time by a factor of eight to acquire TE-averaged spectra in three spatial dimensions. Simulation of glutamate and glutamine showed that the 2.2-2.4 ppm spectral region contained 95% glutamate signal using the TE-averaged method. Peak integration of this spectral range and home-developed, prior-knowledge-based fitting were used for quantitation. Gray matter brain phantom measurements were acquired on a Siemens 3 T Trio scanner. Non-uniform sampling was applied retrospectively to these phantom measurements and quantitative results of glutamate with respect to creatine 3.0 (Glu/Cr) ratios showed a coefficient of variance of 16% for peak integration and 9% for peak fitting using eight-fold acceleration. In vivo scans of the human brain were acquired as well and five different brain regions were quantified using the prior-knowledge-based algorithm. Glu/Cr ratios from these regions agreed with previously reported results in the literature. The method described here, called accelerated TE-averaged echo planar spectroscopic imaging (TEA-EPSI), is a significant methodological advancement and may be a useful tool for categorizing glutamate changes in pathologies where affected brain regions are not known a priori. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Perisinakis, Kostas; Seimenis, Ioannis; Tzedakis, Antonis
Purpose: To determine patient-specific absorbed peak doses to skin, eye lens, brain parenchyma, and cranial red bone marrow (RBM) of adult individuals subjected to low-dose brain perfusion CT studies on a 256-slice CT scanner, and investigate the effect of patient head size/shape, head position during the examination and bowtie filter used on peak tissue doses. Methods: The peak doses to eye lens, skin, brain, and RBM were measured in 106 individual-specific adult head phantoms subjected to the standard low-dose brain perfusion CT on a 256-slice CT scanner using a novel Monte Carlo simulation software dedicated for patient CT dosimetry. Peakmore » tissue doses were compared to corresponding thresholds for induction of cataract, erythema, cerebrovascular disease, and depression of hematopoiesis, respectively. The effects of patient head size/shape, head position during acquisition and bowtie filter used on resulting peak patient tissue doses were investigated. The effect of eye-lens position in the scanned head region was also investigated. The effect of miscentering and use of narrow bowtie filter on image quality was assessed. Results: The mean peak doses to eye lens, skin, brain, and RBM were found to be 124, 120, 95, and 163 mGy, respectively. The effect of patient head size and shape on peak tissue doses was found to be minimal since maximum differences were less than 7%. Patient head miscentering and bowtie filter selection were found to have a considerable effect on peak tissue doses. The peak eye-lens dose saving achieved by elevating head by 4 cm with respect to isocenter and using a narrow wedge filter was found to approach 50%. When the eye lies outside of the primarily irradiated head region, the dose to eye lens was found to drop to less than 20% of the corresponding dose measured when the eye lens was located in the middle of the x-ray beam. Positioning head phantom off-isocenter by 4 cm and employing a narrow wedge filter results in a moderate reduction of signal-to-noise ratio mainly to the peripheral region of the phantom. Conclusions: Despite typical peak doses to skin, eye lens, brain, and RBM from the standard low-dose brain perfusion 256-slice CT protocol are well below the corresponding thresholds for the induction of erythema, cataract, cerebrovascular disease, and depression of hematopoiesis, respectively, every effort should be made toward optimization of the procedure and minimization of dose received by these tissues. The current study provides evidence that the use of the narrower bowtie filter available may considerably reduce peak absorbed dose to all above radiosensitive tissues with minimal deterioration in image quality. Considerable reduction in peak eye-lens dose may also be achieved by positioning patient head center a few centimeters above isocenter during the exposure.« less
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Dadvand, Payam; Pujol, Jesus; Macià, Dídac; Martínez-Vilavella, Gerard; Blanco-Hinojo, Laura; Mortamais, Marion; Alvarez-Pedrerol, Mar; Fenoll, Raquel; Esnaola, Mikel; Dalmau-Bueno, Albert; López-Vicente, Mónica; Basagaña, Xavier; Jerrett, Michael; Nieuwenhuijsen, Mark J; Sunyer, Jordi
2018-02-23
Proponents of the biophilia hypothesis believe that contact with nature, including green spaces, has a crucial role in brain development in children. Currently, however, we are not aware of evidence linking such exposure with potential effects on brain structure. We determined whether lifelong exposure to residential surrounding greenness is associated with regional differences in brain volume based on 3-dimensional magnetic resonance imaging (3D MRI) among children attending primary school. We performed a series of analyses using data from a subcohort of 253 Barcelona schoolchildren from the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) project. We averaged satellite-based normalized difference vegetation index (NDVI) across 100-m buffers around all residential addresses since birth to estimate each participant's lifelong exposure to residential surrounding greenness, and we used high-resolution 3D MRIs of brain anatomy to identify regional differences in voxel-wise brain volume associated with greenness exposure. In addition, we performed a supporting substudy to identify regional differences in brain volume associated with measures of working memory ( d' from computerized n -back tests) and inattentiveness (hit reaction time standard error from the Attentional Network Task instrument) that were repeated four times over one year. We also performed a second supporting substudy to determine whether peak voxel tissue volumes in brain regions associated with residential greenness predicted cognitive function test scores. Lifelong exposure to greenness was positively associated with gray matter volume in the left and right prefrontal cortex and in the left premotor cortex and with white matter volume in the right prefrontal region, in the left premotor region, and in both cerebellar hemispheres. Some of these regions partly overlapped with regions associated with cognitive test scores (prefrontal cortex and cerebellar and premotor white matter), and peak volumes in these regions predicted better working memory and reduced inattentiveness. Our findings from a study population of urban schoolchildren in Barcelona require confirmation, but they suggest that being raised in greener neighborhoods may have beneficial effects on brain development and cognitive function. https://doi.org/10.1289/EHP1876.
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Effect of Growth Hormone Deficiency on Brain Structure, Motor Function and Cognition
ERIC Educational Resources Information Center
Webb, Emma A.; O'Reilly, Michelle A.; Clayden, Jonathan D.; Seunarine, Kiran K.; Chong, Wui K.; Dale, Naomi; Salt, Alison; Clark, Chris A.; Dattani, Mehul T.
2012-01-01
The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone less than 6.7 [micro]g/l) and idiopathic short stature (peak growth hormone greater than 10 [micro]g/l)…
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NASA Astrophysics Data System (ADS)
Iwaskiw, A. S.; Ott, K. A.; Armiger, R. S.; Wickwire, A. C.; Alphonse, V. D.; Voo, L. M.; Carneal, C. M.; Merkle, A. C.
2018-01-01
The experimental measurement of biomechanical responses that correlate with blast-induced traumatic brain injury (bTBI) has proven challenging. These data are critical for both the development and validation of computational and physical head models, which are used to quantify the biomechanical response to blast as well as to assess fidelity of injury mitigation strategies, such as personal protective equipment. Therefore, foundational postmortem human surrogate (PMHS) experimental data capturing the biomechanical response are necessary for human model development. Prior studies have measured short-duration pressure transmission to the brain (Kinetic phase), but have failed to reproduce and measure the longer-duration inertial loading that can occur (Kinematic phase). Four fully instrumented PMHS were subjected to short-duration dynamic overpressure in front-facing and rear-facing orientations, where intracranial pressure (ICP), global head kinematics, and brain motion (as measured by high-speed X-ray) with respect to the skull were recorded. Peak ICP results generally increased with increased dose, and a mirrored pressure response was seen when comparing the polarity of frontal bone versus occipital bone ICP sensors. The head kinematics were delayed when compared to the pressure response and showed higher peak angles for front-facing tests as compared to rear-facing. Brain displacements were approximately 2-6 mm, and magnitudes did not change appreciably between front- and rear-facing tests. These data will be used to inform and validate models used to assess bTBI.
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Ciejka, Elżbieta; Skibska, Beata; Gorąca, Anna
2017-06-27
The human population is exposed ever more frequently to magnetic fields (MF). This is due to both technological progress and development of the economy as well as to advances made in medical science. That is why the thorough understanding and systematized knowledge about mechanisms by which MF exerts its effects on living organisms play such an important role. In this context the health of MF-exposed people is the subject of particular concern. The aim of the study was to evaluate the effect of extremely low frequency magnetic field (ELFMF) used in magnetotherapy on the concentration of interleukin 6 (IL-6) in rat heart and brain. The male rats were randomly divided into 3 experimental groups: group I - control, without contact with magnetic field; group II - exposed to bipolar, rectangular magnetic field 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks; and group III - exposed to bipolar, rectangular magnetic field 40 Hz, 7 mT 60 min/day for 2 weeks. Concentration of IL-6 in the heart and brain of animals was measured after MF exposure. Exposure to ELFMF: 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks caused a significant IL-6 increase in rat hearts compared to the control group (p < 0.05) and a non-significant IL-6 decrease in rat brain. The magnetic field applied for 60 min resulted in non-significant IL-6 increase in rat hearts compared to the control group and significant IL-6 decrease in rat brain (p < 0.05). The influence of magnetic field on inflammation in the body varies depending on the MF parameters and the affected tissues or cells. Med Pr 2017;68(4):517-523. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.
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Takeuchi, T; Sitizyo, K; Harada, E
1998-03-01
The postnatal development of the central nervous system (CNS) in house musk shrew in the early stage of maturation was studied. The electroencephalogram (EEG) and visual evoked potential (VEP) in association with catecholamine contents and myelin basic protein (MBP) immunoreactivity were carried out from the 1st to the 20th day of postnatal age. Different EEG patterns which were specific to behavioral states (awake and drowsy) were first recorded on the 5th day, and the total power which was obtained by power spectrum analysis increased after this stage. The latencies of all peaks in VEP markedly shortened between the 5th and the 7th day. Noradrenalin (NA) content of the brain showed a slight increase after the 3rd day, and reached maximum levels on the 7th day, which was delayed a few days compared to dopamine (DA). In hyperthyroidism, the peak latency of VEP was shortened and biosynthesis of NA in cerebral cortex and DA in hippocampus was accelerated. The most obvious change in MBP-immunoreactivity of the telencephalon occurred from the 7th to the 10th day. These morphological changes in the brain advanced at the identical time-course to those in the electrophysiological development and increment of DA and NA contents.
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Epileptic rat brain tissue analyzed by 2D correlation Raman spectroscopy
NASA Astrophysics Data System (ADS)
Sacharz, Julia; Wesełucha-Birczyńska, Aleksandra; Zięba-Palus, Janina; Lewandowski, Marian H.; Kowalski, Rafał; Palus, Katarzyna; Chrobok, Łukasz; Moskal, Paulina; Birczyńska, Malwina; Sozańska, Agnieszka
2018-01-01
Absence epilepsy is the neurological disorder characterized by the pathological spike-and wave discharges present in the electroencephalogram, accompanying a sudden loss of consciousness. Experiments were performed on brain slices obtained from young male WAG/Rij rats (2-3 weeks old), so that they were sampled before the appearance of brain-damaging seizures symptoms. Two differing brain areas of the rats' brain tissue were studied: the somatosensory cortex (Sc) and the dorsal lateral geniculate nucleus of the thalamus (DLG). The Raman spectra of the fresh brain scraps, kept during measurements in artificial cerebrospinal fluid, were collected using as an excitation source 442 nm, 514.5 nm, 785 nm and 1064 nm laser line. The average spectra were analyzed by 2D correlation method regarding laser line as an external perturbation. In 2D synchronous spectra positive auto-peaks corresponding to the Cdbnd C stretching and amide I band vibrations show maxima at 1660 cm- 1 and 1662 cm- 1 for Sc and DLG, respectively. The prominent auto-peak at 2937 cm- 1, originated from the CH3 mode in DLG brain area, seems to indicate the importance of methylation, considered to be significant in epileptogenesis. Synchronous and asynchronous correlations peaks, glutamic acid and gamma-aminobutyric acid (GABA), appear in Sc and DLG, respectively. In the 1730-1600 cm- 1 range occur cross-peaks which appearance might be triggered by glial fibrillary acidic protein (GFAP) activation.
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NASA Astrophysics Data System (ADS)
Petrov, Irene Y.; Petrov, Yuriy; Prough, Donald S.; Richardson, C. Joan; Fonseca, Rafael A.; Robertson, Claudia S.; Asokan, C. Vasantha; Agbor, Adaeze; Esenaliev, Rinat O.
2016-03-01
We proposed to use transmission (forward) mode for cerebral, noninvasive, transcranial optoacoustic monitoring, imaging, and sensing in humans. In the transmission mode, the irradiation of the tissue of interest and detection of optoacoustic signals are performed from opposite hemispheres, while in the reflection (backward) mode the irradiation of the tissue of interest and detection of optoacoustic signals are performed from the same hemisphere. Recently, we developed new, transmission-mode optoacoustic probes for patients with traumatic brain injury (TBI) and for neonatal patients. The transmission mode probes have two major parts: a fiber-optic delivery system and an acoustic transducer (sensor). To obtain optoacoustic signals in the transmission mode, in this study we placed the sensor on the forehead, while light was delivered to the opposite side of the head. Using a medical grade, multi-wavelength, OPObased optoacoustic system tunable in the near infrared spectral range (680-950 nm) and a novel, compact, fiber-coupled, multi-wavelength, pulsed laser diode-based system, we recorded optoacoustic signals generated in the posterior part of the head of adults with TBI and neonates. The optoacoustic signals had two distinct peaks: the first peak from the intracranial space and the second peak from the scalp. The first peak generated by cerebral blood was used to measure cerebral blood oxygenation. Moreover, the transmission mode measurements provided detection of intracranial hematomas in the TBI patients. The obtained results suggest that the transmission mode can be used for optoacoustic brain imaging, tomography, and mapping in humans.
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2015-01-01
Quantifying glycogen synthase kinase-3 (GSK-3) activity in vivo using positron emission tomography (PET) imaging is of interest because dysregulation of GSK-3 is implicated in numerous diseases and neurological disorders for which GSK-3 inhibitors are being considered as therapeutic strategies. Previous PET radiotracers for GSK-3 have been reported, but none of the published examples cross the blood–brain barrier. Therefore, we have an ongoing interest in developing a brain penetrating radiotracer for GSK-3. To this end, we were interested in synthesis and preclinical evaluation of [11C]SB-216763, a high-affinity inhibitor of GSK-3 (Ki = 9 nM; IC50 = 34 nM). Initial radiosyntheses of [11C]SB-216763 proved ineffective in our hands because of competing [3 + 3] sigmatropic shifts. Therefore, we have developed a novel one-pot two-step synthesis of [11C]SB-216763 from a 2,4-dimethoxybenzyl-protected maleimide precursor, which provided high specific activity [11C]SB-216763 in 1% noncorrected radiochemical yield (based upon [11C]CH3I) and 97–100% radiochemical purity (n = 7). Initial preclinical evaluation in rodent and nonhuman primate PET imaging studies revealed high initial brain uptake (peak rodent SUV = 2.5 @ 3 min postinjection; peak nonhuman primate SUV = 1.9 @ 5 min postinjection) followed by washout. Brain uptake was highest in thalamus, striatum, cortex, and cerebellum, areas known to be rich in GSK-3. These results make the arylindolemaleimide skeleton our lead scaffold for developing a PET radiotracer for quantification of GSK-3 density in vivo and ultimately translating it into clinical use. PMID:26005531
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von Holst, Hans; Li, Xiaogai
2013-01-01
There is a lack of knowledge about the direct neuromechanical consequences in traumatic brain injury (TBI) at the scene of accident. In this study we use a finite element model of the human head to study the dynamic response of the brain during the first milliseconds after the impact with velocities of 10, 6, and 2 meters/second (m/s), respectively. The numerical simulation was focused on the external kinetic energy transfer, intracranial pressure (ICP), strain energy density and first principal strain level, and their respective impacts to the brain tissue. We show that the oblique impacts of 10 and 6 m/s resulted in substantial high peaks for the ICP, strain energy density, and first principal strain levels, however, with different patterns and time frames. Also, the 2 m/s impact showed almost no increase in the above mentioned investigated parameters. More importantly, we show that there clearly exists a dynamic triple peak impact factor to the brain tissue immediately after the impact regardless of injury severity associated with different impact velocities. The dynamic triple peak impacts occurred in a sequential manner first showing strain energy density and ICP and then followed by first principal strain. This should open up a new dimension to better understand the complex mechanisms underlying TBI. Thus, it is suggested that the combination of the dynamic triple peak impacts to the brain tissue may interfere with the cerebral metabolism relative to the impact severity thereby having the potential to differentiate between severe and moderate TBI from mild TBI.
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Immunoreactive dynorphin in pituitary and brain.
Goldstein, A; Ghazarossian, V E
1980-01-01
Distribution of the potent opioid peptide dynorphin has been determined in pituitary gland (pig, beef, rat), in the various regions of rat brain, and in rat spinal cord, by using a highly specific antiserum. By gel permeation chromatography in 4 M guanidine, the porcine pituitary immunoreactivity is found in a major peak of apparent molecular weight about 1700 and a minor peak of about 3400. Similar peaks are found in rat pituitary extracts, whereas rat brain contains, in addition, two peaks of larger apparent molecular weight. In the pituitary, immunoreactive dynorphin is found predominantly in pars nervosa. In the central nervous system, it is distributed widely, with highest concentrations in hypothalamus, medulla-pons, midbrain, and spinal cord. Although dynorphin contains leucine-enkephalin, the regional distribution of dynorphin is different from that of enkephalin or of any other known opioid peptide. PMID:6108564
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Pharmacokinetics and Metabolism of 4R-Cembranoid.
Vélez-Carrasco, Wanda; Green, Carol E; Catz, Paul; Furimsky, Anna; O'Loughlin, Kathleen; Eterović, Vesna A; Ferchmin, P A
2015-01-01
4R-cembranoid (4R) is a natural cyclic diterpenoid found in tobacco leaves that displays neuroprotective activity. 4R protects against NMDA, paraoxon (POX), and diisopropylfluorophosphate (DFP) damage in rat hippocampal slices and against DFP in rats in vivo. The purpose of this study was to examine the metabolism and pharmacokinetics of 4R as part of its preclinical development as a neuroprotective drug. 10 µM 4R was found to be very stable in plasma for up to 1 hr incubation. 4R metabolism in human microsomes was faster than in the rat. Ten metabolites of 4R were detected in the microsomal samples; 6 dihydroxy and 4 monohydroxy forms of 4R. Male rats received a single dose of 4R at 6 mg/kg i.v., i.m., or s.c. The i.v. group had the highest plasma concentration of 1017 ng/mL. The t1/2 was 36 min and reached the brain within 10 min. The brain peak concentration was 6516 ng/g. The peak plasma concentration in the i.m. group was 163 ng/mL compared to 138 ng/mL in the s.c. group. The t1/2 of 4R after i.m. and s.c. administration was approximately 1.5 hr. The brain peak concentration was 329 ng/g in the i.m. group and 323 ng/g for the s.c. group. The brain to plasma ratio in the i.v. group was 6.4, reached 10 min after dose, whereas in the i.m. and s.c. groups was 2.49 and 2.48, respectively, at 90 min after dose. Our data show that 4R crosses the BBB and concentrates in the brain where it exerts its neuroprotective effect.
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Pharmacokinetics and Metabolism of 4R-Cembranoid
Vélez-Carrasco, Wanda; Green, Carol E.; Catz, Paul; Furimsky, Anna; O’Loughlin, Kathleen; Eterović, Vesna A.; Ferchmin, P. A.
2015-01-01
4R-cembranoid (4R) is a natural cyclic diterpenoid found in tobacco leaves that displays neuroprotective activity. 4R protects against NMDA, paraoxon (POX), and diisopropylfluorophosphate (DFP) damage in rat hippocampal slices and against DFP in rats in vivo. The purpose of this study was to examine the metabolism and pharmacokinetics of 4R as part of its preclinical development as a neuroprotective drug. 10 µM 4R was found to be very stable in plasma for up to 1 hr incubation. 4R metabolism in human microsomes was faster than in the rat. Ten metabolites of 4R were detected in the microsomal samples; 6 dihydroxy and 4 monohydroxy forms of 4R. Male rats received a single dose of 4R at 6 mg/kg i.v., i.m., or s.c. The i.v. group had the highest plasma concentration of 1017 ng/mL. The t1/2 was 36 min and reached the brain within 10 min. The brain peak concentration was 6516 ng/g. The peak plasma concentration in the i.m. group was 163 ng/mL compared to 138 ng/mL in the s.c. group. The t1/2 of 4R after i.m. and s.c. administration was approximately 1.5 hr. The brain peak concentration was 329 ng/g in the i.m. group and 323 ng/g for the s.c. group. The brain to plasma ratio in the i.v. group was 6.4, reached 10 min after dose, whereas in the i.m. and s.c. groups was 2.49 and 2.48, respectively, at 90 min after dose. Our data show that 4R crosses the BBB and concentrates in the brain where it exerts its neuroprotective effect. PMID:25811857
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Connor, Richard C
2007-04-29
Bottlenose dolphins in Shark Bay, Australia, live in a large, unbounded society with a fission-fusion grouping pattern. Potential cognitive demands include the need to develop social strategies involving the recognition of a large number of individuals and their relationships with others. Patterns of alliance affiliation among males may be more complex than are currently known for any non-human, with individuals participating in 2-3 levels of shifting alliances. Males mediate alliance relationships with gentle contact behaviours such as petting, but synchrony also plays an important role in affiliative interactions. In general, selection for social intelligence in the context of shifting alliances will depend on the extent to which there are strategic options and risk. Extreme brain size evolution may have occurred more than once in the toothed whales, reaching peaks in the dolphin family and the sperm whale. All three 'peaks' of large brain size evolution in mammals (odontocetes, humans and elephants) shared a common selective environment: extreme mutual dependence based on external threats from predators or conspecific groups. In this context, social competition, and consequently selection for greater cognitive abilities and large brain size, was intense.
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CT Perfusion in Acute Stroke: "Black Holes" on Time-to-Peak Image Maps Indicate Unsalvageable Brain.
Meagher, Ruairi; Shankar, Jai Jai Shiva
2016-11-01
CT perfusion is becoming important in acute stroke imaging to determine optimal patient-management strategies. The purpose of this study was to examine the predictive value of time-to-peak image maps and, specifically, a phenomenon coined a "black hole" for assessing infarcted brain tissue at the time of scan. Acute stroke patients were screened for the presence of black holes and their follow-up imaging (noncontrast CT or MR) was reviewed to assess for infarcted brain tissue. Of the 23 patients with signs of acute ischemia on CT perfusion, all had black holes. The black holes corresponded with areas of infarcted brain on follow-up imaging (specificity 100%). Black holes demonstrated significantly lower cerebral blood volumes (P < .001) and cerebral blood flow (P < .001) compared to immediately adjacent tissue. Black holes on time-to-peak image maps represent areas of unsalvageable brain. Copyright © 2016 by the American Society of Neuroimaging.
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Purcell, Jeremy J.; Rapp, Brenda
2013-01-01
Previous research has shown that damage to the neural substrates of orthographic processing can lead to functional reorganization during reading (Tsapkini et al., 2011); in this research we ask if the same is true for spelling. To examine the functional reorganization of spelling networks we present a novel three-stage Individual Peak Probability Comparison (IPPC) analysis approach for comparing the activation patterns obtained during fMRI of spelling in a single brain-damaged individual with dysgraphia to those obtained in a set of non-impaired control participants. The first analysis stage characterizes the convergence in activations across non-impaired control participants by applying a technique typically used for characterizing activations across studies: Activation Likelihood Estimate (ALE) (Turkeltaub et al., 2002). This method was used to identify locations that have a high likelihood of yielding activation peaks in the non-impaired participants. The second stage provides a characterization of the degree to which the brain-damaged individual's activations correspond to the group pattern identified in Stage 1. This involves performing a Mahalanobis distance statistics analysis (Tsapkini et al., 2011) that compares each of a control group's peak activation locations to the nearest peak generated by the brain-damaged individual. The third stage evaluates the extent to which the brain-damaged individual's peaks are atypical relative to the range of individual variation among the control participants. This IPPC analysis allows for a quantifiable, statistically sound method for comparing an individual's activation pattern to the patterns observed in a control group and, thus, provides a valuable tool for identifying functional reorganization in a brain-damaged individual with impaired spelling. Furthermore, this approach can be applied more generally to compare any individual's activation pattern with that of a set of other individuals. PMID:24399981
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Hirashima, A; Hirokado, S; Ohta, H; Suetsugu, E; Sakaguchi, M; Kuwano, E; Taniguchi, E; Eto, M
1999-09-01
At day two, a sharp peak of octopamine (OA) was observed in last instar female Bombyx mori larvae. This peak also appeared in male larvae a day later than in females at day three. An OA peak was also observed before the 3rd ecdysis. However, no OA peaks were observed in 4th instar larvae. At day eight and nine of the 5th instar, another OA peak was observed for male and female, respectively. A peak of tyramine (TA) was found at day one followed by a peak of OA at day two in 3rd instar larvae. At day two, a day before OA peak, a peak of TA was observed for male insects and before the 2nd peak of OA, TA titre was also high in 5th instar larvae. Immediately after 3rd ecdysis, a high titre of DL-beta-(3,4-dihydroxyphenyl)alanine (DOPA) was observed, followed by a peak of dopamine (DA) at day five. A peak of DOPA was found at day one followed by a peak of DA at day two in 3rd instar larvae. Similarly, a small peak of DOPA was observed at day two, followed by an increase of DA at days eight and nine after the 4th ecdysis. Ecdysteroid peaks were observed just before the 3rd and 4th ecdysis and an ecdysteroid titre increased after the start of spinning. The effects of OA and JH on production of ecdysteroids by prothoracic glands (PGs) were examined in order to identify neuromediators responsible for triggering pupation in B. mori larvae. Exogeneous OA (10-100 mM) reduced and 10 &mgr;M OA stimulated the production of ecdysteroids in the presence and absence of brain extracts by PGs in the final instar (day five) of B. mori in vitro. Meanwhile, exogeneous JHI (10 &mgr;g/ml) stimulated and at 5 &mgr;g/ml it reduced production of ecdysteroids in the presence of brain extracts. Gramine, an OA antagonist, delayed pupation when applied in the diet. Thus, OA may produce some biological effects on the programming of larval-pupal development.
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Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling; Lai, Ted Weita
2017-01-01
Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8-24 h, whereas the late phase of BBB disruption begins 48-58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison to the inhibitors of the neuronal death signaling cascade; these, in fact, can attenuate the infarct volume measured at 24 h post-ischemia when administered at 6 h in our same stroke model.
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Howell, Brett A; Chauhan, Anuj
2010-08-01
Physiologically based pharmacokinetic (PBPK) models were developed for design and optimization of liposome therapy for treatment of overdoses of tricyclic antidepressants and local anesthetics. In vitro drug-binding data for pegylated, anionic liposomes and published mechanistic equations for partition coefficients were used to develop the models. The models were proven reliable through comparisons to intravenous data. The liposomes were predicted to be highly effective at treating amitriptyline overdoses, with reductions in the area under the concentration versus time curves (AUC) of 64% for the heart and brain. Peak heart and brain drug concentrations were predicted to drop by 20%. Bupivacaine AUC and peak concentration reductions were lower at 15.4% and 17.3%, respectively, for the heart and brain. The predicted pharmacokinetic profiles following liposome administration agreed well with data from clinical studies where protein fragments were administered to patients for overdose treatment. Published data on local cardiac function were used to relate the predicted concentrations in the body to local pharmacodynamic effects in the heart. While the results offer encouragement for future liposome therapies geared toward overdose, it is imperative to point out that animal experiments and phase I clinical trials are the next steps to ensuring the efficacy of the treatment. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association
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Bolander, Richard; Mathie, Blake; Bir, Cynthia; Ritzel, David; VandeVord, Pamela
2011-10-01
The manner in which energy from an explosion is transmitted into the brain is currently a highly debated topic within the blast injury community. This study was conducted to investigate the injury biomechanics causing blast-related neurotrauma in the rat. Biomechanical responses of the rat head under shock wave loading were measured using strain gauges on the skull surface and a fiber optic pressure sensor placed within the cortex. MicroCT imaging techniques were applied to quantify skull bone thickness. The strain gauge results indicated that the response of the rat skull is dependent on the intensity of the incident shock wave; greater intensity shock waves cause greater deflections of the skull. The intracranial pressure (ICP) sensors indicated that the peak pressure developed within the brain was greater than the peak side-on external pressure and correlated with surface strain. The bone plates between the lambda, bregma, and midline sutures are probable regions for the greatest flexure to occur. The data provides evidence that skull flexure is a likely candidate for the development of ICP gradients within the rat brain. This dependency of transmitted stress on particular skull dynamics for a given species should be considered by those investigating blast-related neurotrauma using animal models.
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Yamaguchi, Shinji; Hayase, Shin; Aoki, Naoya; Takehara, Akihiko; Ishigohoka, Jun; Matsushima, Toshiya; Wada, Kazuhiro; Homma, Koichi J
2017-01-01
Thyroid hormones are closely linked to the hatching process in precocial birds. Previously, we showed that thyroid hormones in brain had a strong impact on filial imprinting, an early learning behavior in newly hatched chicks; brain 3,5,3'-triiodothyronine (T3) peaks around hatching and imprinting training induces additional T3 release, thus, extending the sensitive period for imprinting and enabling subsequent other learning. On the other hand, blood thyroid hormone levels have been reported to increase gradually after hatching in altricial species, but it remains unknown how the brain thyroid hormone levels change during post-hatching development of altricial birds. Here, we determined the changes in serum and brain thyroid hormone levels of a passerine songbird species, the zebra finch using radioimmunoassay. In the serum, we found a gradual increase in thyroid hormone levels during post-hatching development, as well as differences between male and female finches. In the brain, there was clear surge in the hormone levels during development in males and females coinciding with the time of fledging, but the onset of the surge of thyroxine (T4) in males preceded that of females, whereas the onset of the surge of T3 in males succeeded that of females. These findings provide a basis for understanding the functions of thyroid hormones during early development and learning in altricial birds.
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Kubota, Kazuo; Saito, Yoshiaki; Ohba, Chihiro; Saitsu, Hirotomo; Fukuyama, Tetsuhiro; Ishiyama, Akihiko; Saito, Takashi; Komaki, Hirofumi; Nakagawa, Eiji; Sugai, Kenji; Sasaki, Masayuki; Matsumoto, Naomichi
2015-01-01
A boy with spastic paraplegia type 2 (SPG2) due to a novel splice site mutation of PLP1 presented with progressive spasticity of lower limbs, which was first observed during late infancy, when he gained the ability to walk with support. His speech was slow and he had dysarthria. The patient showed mildly delayed intellectual development. Subtotal dysmyelination in the central nervous system was revealed, which was especially prominent in structures known to be myelinated during earlier period, whereas structures that are myelinated later were better myelinated. These findings on the brain magnetic resonance imaging were unusual for subjects with PLP1 mutations. Peaks I and II of the auditory brainstem response (ABR) were normally provoked, but peaks III-V were not clearly demarcated, similarly to the findings in Pelizaeus-Merzbacher disease. These findings of brain MRI and ABR may be characteristic for a subtype of SPG2 patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
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Annexin A7 Levels Increase in Rats With Traumatic Brain Injury and Promote Secondary Brain Injury.
Gao, Fan; Li, Di; Rui, Qin; Ni, Haibo; Liu, Huixiang; Jiang, Feng; Tao, Li; Gao, Rong; Dang, Baoqi
2018-01-01
The incidence of traumatic brain injury (TBI) has been increasing annually. Annexin A7 is a calcium-dependent phospholipid binding protein. It can promote melting of the cell membrane. Recent studies have shown that it plays an important role in atherosclerosis, other cardiovascular diseases, and a variety of tumors. However, few studies of ANXA7 in TBI have been performed. We here observed how ANXA7 changes after TBI and discuss whether brain injury is associated with the use of ANXA7 antagonist intervention. Experimental Results: 1. After TBI, ANXA7 levels were higher than in the sham group, peaking 24 h after TBI. 2. The use of siA7 was found to reduce the expression of A7 in the injured brain tissue, and also brain edema, BBB damage, cell death, and apoptosis relative to the sham group. Conclusion: ANXA7 promotes the development of secondary brain injury (SBI) after TBI.
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Developing an Adaptability Training Strategy and Policy for the DoD
2008-10-01
might include monitoring of trainees using electroencephalogram ( EEG ) technology to gain neurofeedback during scenario performance. In order to...group & adequate sample; pre and post iii. Possibly including EEG monitoring (and even neurofeedback ) 4. Should seek to determine general...Dr. John Cowan has developed a system called the Peak Achievement Trainer (PAT) EEG , which traces electrical activity in the brain and provides
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Performance evaluation of neuro-PET using silicon photomultipliers
NASA Astrophysics Data System (ADS)
Jung, Jiwoong; Choi, Yong; Jung, Jin Ho; Kim, Sangsu; Im, Ki Chun
2016-05-01
Recently, we have developed the second prototype Silicon photomultiplier (SiPM) based positron emission tomography (PET) scanner for human brain imaging. The PET system was comprised of detector block which consisted of 4×4 SiPMs and 4×4 Lutetium Yttrium Orthosilicate arrays, charge signal transmission method, high density position decoder circuit and FPGA-embedded ADC boards. The purpose of this study was to evaluate the performance of the newly developed neuro-PET system. The energy resolution, timing resolution, spatial resolution, sensitivity, stability of the photo-peak position and count rate performance were measured. Tomographic image of 3D Hoffman brain phantom was also acquired to evaluate imaging capability of the neuro-PET. The average energy and timing resolutions measured for 511 keV gamma rays were 17±0.1% and 3±0.3 ns, respectively. Spatial resolution and sensitivity at the center of field of view (FOV) were 3.1 mm and 0.8%, respectively. The average scatter fraction was 0.4 with an energy window of 350-650 keV. The maximum true count rate and maximum NECR were measured as 43.3 kcps and 6.5 kcps at an activity concentration of 16.7 kBq/ml and 5.5 kBq/ml, respectively. Long-term stability results show that there was no significant change in the photo-peak position, energy resolution and count rate for 60 days. Phantom imaging studies were performed and they demonstrated the feasibility for high quality brain imaging. The performance tests and imaging results indicate that the newly developed PET is useful for brain imaging studies, if the axial FOV is extended to improve the system sensitivity.
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Germline Chd8 haploinsufficiency alters brain development in mouse
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gompers, Andrea L.; Su-Feher, Linda; Ellegood, Jacob
The chromatin remodeling gene CHD8 represents a central node in neurodevelopmental gene networks implicated in autism. In this paper, we examined the impact of germline heterozygous frameshift Chd8 mutation on neurodevelopment in mice. Chd8 +/ del5 mice displayed normal social interactions with no repetitive behaviors but exhibited cognitive impairment correlated with increased regional brain volume, validating that phenotypes of Chd8 +/ del5 mice overlap pathology reported in humans with CHD8 mutations. We applied network analysis to characterize neurodevelopmental gene expression, revealing widespread transcriptional changes in Chd8 +/ del5 mice across pathways disrupted in neurodevelopmental disorders, including neurogenesis, synaptic processes andmore » neuroimmune signaling. We identified a co-expression module with peak expression in early brain development featuring dysregulation of RNA processing, chromatin remodeling and cell-cycle genes enriched for promoter binding by Chd8, and we validated increased neuronal proliferation and developmental splicing perturbation in Chd8 +/ del5 mice. Finally, this integrative analysis offers an initial picture of the consequences of Chd8 haploinsufficiency for brain development.« less
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Germline Chd8 haploinsufficiency alters brain development in mouse
Gompers, Andrea L.; Su-Feher, Linda; Ellegood, Jacob; ...
2017-06-26
The chromatin remodeling gene CHD8 represents a central node in neurodevelopmental gene networks implicated in autism. In this paper, we examined the impact of germline heterozygous frameshift Chd8 mutation on neurodevelopment in mice. Chd8 +/ del5 mice displayed normal social interactions with no repetitive behaviors but exhibited cognitive impairment correlated with increased regional brain volume, validating that phenotypes of Chd8 +/ del5 mice overlap pathology reported in humans with CHD8 mutations. We applied network analysis to characterize neurodevelopmental gene expression, revealing widespread transcriptional changes in Chd8 +/ del5 mice across pathways disrupted in neurodevelopmental disorders, including neurogenesis, synaptic processes andmore » neuroimmune signaling. We identified a co-expression module with peak expression in early brain development featuring dysregulation of RNA processing, chromatin remodeling and cell-cycle genes enriched for promoter binding by Chd8, and we validated increased neuronal proliferation and developmental splicing perturbation in Chd8 +/ del5 mice. Finally, this integrative analysis offers an initial picture of the consequences of Chd8 haploinsufficiency for brain development.« less
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García-García, Alejandro G; Polo-Hernández, Erica; Tabernero, Arantxa; Medina, José M
2015-10-22
We have previously shown that serum albumin controls perinatal rat brain development through the regulation of oleic acid synthesis by astrocytes. In fact, oleic acid synthesized and released by astrocytes promoted neurite growth, neuron migration and the arrangement of prospective synapses. In this work we show that alpha-fetoprotein (AFP) is also present in the brain during embryonic development, its concentrations peaking at E15.5 and at E19.5. However, after E19.5 AFP concentrations plummeted concurrently with a sharp increase in serum albumin concentrations. At E15.5, AFP is present in caudal regions of the brain, particularly in brain areas undergoing differentiation during this period, such as the thalamic reticular nucleus of the thalamus, the hypothalamus, the amygdala and the hippocampus. Albumin was not detected in the brain at E15.5 but stained brain cells substantially on day E19.5, showing a very similar distribution to that of AFP under the same circumstances. The concentrations of free oleic acid in the brain were inversely correlated with those of AFP, suggesting that the signals elicited by AFP and oleic acid can be inversely associated. GAP-43, a marker of axonal growth that is highly expressed by the presence of oleic acid, was not co-localized with AFP except in the marginal zone and areas delimiting the subplate. AFP prevented the increase in GAP-43 expression caused by the presence of oleic acid in neurons in primary culture in vitro and in organotypic cultures of embryonic rat brain ex vivo, suggesting that AFP may modulate the effect of serum albumin on brain development. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
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Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease
NASA Astrophysics Data System (ADS)
Shi, Lingyan; Shumyatsky, Pavel; Rodríguez-Contreras, Adrián; Alfano, Robert
2016-01-01
The terahertz (THz) absorption and index of refraction of brain tissues from a mouse model of Alzheimer's disease (AD) and a control wild-type (normal) mouse were compared using THz time-domain spectroscopy (THz-TDS). Three dominating absorption peaks associated to torsional-vibrational modes were observed in AD tissue, at about 1.44, 1.8, and 2.114 THz, closer to the peaks of free tryptophan molecules than in normal tissue. A possible reason is that there is more free tryptophan in AD brain tissue, while in normal brain tissue more tryptophan is attached to other molecules. Our study suggests that THz-absorption modes may be used as an AD biomarker fingerprint in brain, and that THz-TDS is a promising technique for early diagnosis of AD.
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Reyes-Tomassini, José J; Wong, Ten-Tsao; Zohar, Yonathan
2017-06-01
Arginine vasotocin is a hormone produced in the hypothalamus of teleost fish that has been shown to regulate gonad development and sexual behavior. To study the role of arginine vasotocin in the gonadal cycle of the hermaphrodite gilthead seabream, Sparus aurata, we cloned the seabream arginine vasotocin (avt) complementary DNA (cDNA). We investigated the expression of brain avt throughout the gonad cycle using real-time quantitative PCR and compared its expression levels to the expression levels of two key gonadal steroidogenic enzymes, cyp19a1a and cyp11b2. In July, when the process of sex reversal is thought to begin, avt expression was elevated over the previous 2 months. Avt in the brain remained at or above the level of July until November then peaked again in December. There was no difference between males and females in the expression levels of brain avt throughout the year. However, only in ambisexual fish was the expression of the cyp19a1a gonadal aromatase correlated to the expression of avt in the brain. Cyp11b2 did not show any correlation to brain avt expression. We also found that females had more intense body coloration than males and that this intensity peaked prior to spawning. Avt expression and female coloration were positively correlated. The fact that brain avt expression was lowest during gonad quiescence, together with the observation of a correlation between brain avt with gonadal cyp19a1a and body coloration during that time suggests that avt may play a role during the process of sex reversal and spawning of the gilthead seabream.
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Development and validation of a numerical model of the swine head subjected to open-field blasts
NASA Astrophysics Data System (ADS)
Kalra, A.; Zhu, F.; Feng, K.; Saif, T.; Kallakuri, S.; Jin, X.; Yang, K.; King, A.
2017-11-01
A finite element model of the head of a 55-kg Yucatan pig was developed to calculate the incident pressure and corresponding intracranial pressure due to the explosion of 8 lb (3.63 kg) of C4 at three different distances. The results from the model were validated by comparing findings with experimentally obtained data from five pigs at three different blast overpressure levels: low (150 kPa), medium (275 kPa), and high (400 kPa). The peak values of intracranial pressures from numerical model at different locations of the brain such as the frontal, central, left temporal, right temporal, parietal, and occipital regions were compared with experimental values. The model was able to predict the peak pressure with reasonable percentage differences. The differences for peak incident and intracranial pressure values between the simulation results and the experimental values were found to be less than 2.2 and 29.3%, respectively, at all locations other than the frontal region. Additionally, a series of parametric studies shows that the intracranial pressure was very sensitive to sensor locations, the presence of air bubbles, and reflections experienced during the experiments. Further efforts will be undertaken to correlate the different biomechanical response parameters, such as the intracranial pressure gradient, stress, and strain results obtained from the validated model with injured brain locations once the histology data become available.
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Gilad, O; Horesh, L; Holder, D S
2007-07-01
For the novel application of recording of resistivity changes related to neuronal depolarization in the brain with electrical impedance tomography, optimal recording is with applied currents below 100 Hz, which might cause neural stimulation of skin or underlying brain. The purpose of this work was to develop a method for application of low frequency currents to the scalp, which delivered the maximum current without significant stimulation of skin or underlying brain. We propose a recessed electrode design which enabled current injection with an acceptable skin sensation to be increased from 100 muA using EEG electrodes, to 1 mA in 16 normal volunteers. The effect of current delivered to the brain was assessed with an anatomically realistic finite element model of the adult head. The modelled peak cerebral current density was 0.3 A/m(2), which was 5 to 25-fold less than the threshold for stimulation of the brain estimated from literature review.
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NASA Astrophysics Data System (ADS)
Yamaguchi, Takahiro; Takehara, Hiroaki; Sunaga, Yoshinori; Haruta, Makito; Motoyama, Mayumi; Ohta, Yasumi; Noda, Toshihiko; Sasagawa, Kiyotaka; Tokuda, Takashi; Ohta, Jun
2016-04-01
A self-reset pixel of 15 × 15 µm2 with high signal-to-noise ratio (effective peak SNR ≃64 dB) for an implantable image sensor has been developed for intrinsic signal detection arising from hemodynamic responses in a living mouse brain. For detecting local conversion between oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in brain tissues, an implantable imaging device was fabricated with our newly designed self-reset image sensor and orange light-emitting diodes (LEDs; λ = 605 nm). We demonstrated imaging of hemodynamic responses in the sensory cortical area accompanied by forelimb stimulation of a living mouse. The implantable imaging device for intrinsic signal detection is expected to be a powerful tool to measure brain activities in living animals used in behavioral analysis.
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Zhang, Liying; Makwana, Rahul; Sharma, Sumit
2013-01-01
Blast-induced traumatic brain injury has emerged as a “signature injury” in combat casualty care. Present combat helmets are designed primarily to protect against ballistic and blunt impacts, but the current issue with helmets is protection concerning blasts. In order to delineate the blast wave attenuating capability of the Advanced Combat Helmet (ACH), a finite element (FE) study was undertaken to evaluate the head response against blast loadings with and without helmet using a partially validated FE model of the human head and ACH. Four levels of overpressures (0.27–0.66 MPa) from the Bowen’s lung iso-damage threshold curves were used to simulate blast insults. Effectiveness of the helmet with respect to head orientation was also investigated. The resulting biomechanical responses of the brain to blast threats were compared for human head with and without the helmet. For all Bowen’s cases, the peak intracranial pressures (ICP) in the head ranged from 0.68 to 1.8 MPa in the coup cortical region. ACH was found to mitigate ICP in the head by 10–35%. Helmeted head resulted in 30% lower average peak brain strains and product of strain and strain rate. Among three blast loading directions with ACH, highest reduction in peak ICP (44%) was due to backward blasts whereas the lowest reduction in peak ICP and brain strains was due to forward blast (27%). The biomechanical responses of a human head to primary blast insult exhibited directional sensitivity owing to the different geometry contours and coverage of the helmet construction and asymmetric anatomy of the head. Thus, direction-specific tolerances are needed in helmet design in order to offer omni-directional protection for the human head. The blasts of varying peak overpressures and durations that are believed to produce the same level of lung injury produce different levels of mechanical responses in the brain, and hence “iso-damage” curves for brain injury are likely different than the Bowen curves for lung injury. PMID:23935591
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Hypoxia-ischemia brain damage disrupts brain cholesterol homeostasis in neonatal rats.
Yu, Z; Li, S; Lv, S H; Piao, H; Zhang, Y H; Zhang, Y M; Ma, H; Zhang, J; Sun, C K; Li, A P
2009-08-01
The first 3 weeks of life is the peak time of oligodendrocytes development and also the critical period of cholesterol increasing dramatically in central nervous system in rats. Neonatal hypoxia-ischemia (HI) brain damage happening in this period may disturb the brain cholesterol balance as well as white matter development. To test this hypothesis, postnatal day 7 (P7) Sprague-Dawley rats were subjected to HI insult. Cholesterol concentrations from brain and plasma were measured. White matter integrity was evaluated by densitometric analysis of myelin basic protein (MBP) immunostaining and electron microscopy. Brain TNF-alpha and IL-6 levels were also measured. HI-induced brain cholesterol, but not the plasma cholesterol, levels decreased significantly during the first three days after HI compared with naïve and sham operated rats (p<0.05). Obvious hypomyelination was indicated by marked reductions in MBP immunostaining on both P10 and P14 (p<0.01) and less and thinner myelinated axons were detected on P21 by electron microscopy observation. High expressions of brain TNF-alpha and IL-6 12 h after HI (p<0.05) were also observed. The present work provides evidence that HI insult destroyed brain cholesterol homeostasis, which might be important in the molecular pathology of hypoxic-ischemic white matter injury. Proinflammatory cytokines insulting oligodendrocytes, may cause cholesterol unbalance. Furthermore, specific therapeutic interventions to maintain brain cholesterol balance may be effective for the recovery of white matter function. Georg Thieme Verlag KG Stuttgart New York.
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Spatial and Time Domain Feature of ERP Speller System Extracted via Convolutional Neural Network.
Yoon, Jaehong; Lee, Jungnyun; Whang, Mincheol
2018-01-01
Feature of event-related potential (ERP) has not been completely understood and illiteracy problem remains unsolved. To this end, P300 peak has been used as the feature of ERP in most brain-computer interface applications, but subjects who do not show such peak are common. Recent development of convolutional neural network provides a way to analyze spatial and temporal features of ERP. Here, we train the convolutional neural network with 2 convolutional layers whose feature maps represented spatial and temporal features of event-related potential. We have found that nonilliterate subjects' ERP show high correlation between occipital lobe and parietal lobe, whereas illiterate subjects only show correlation between neural activities from frontal lobe and central lobe. The nonilliterates showed peaks in P300, P500, and P700, whereas illiterates mostly showed peaks in around P700. P700 was strong in both subjects. We found that P700 peak may be the key feature of ERP as it appears in both illiterate and nonilliterate subjects.
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Model for the computation of self-motion in biological systems
NASA Technical Reports Server (NTRS)
Perrone, John A.
1992-01-01
A technique is presented by which direction- and speed-tuned cells, such as those commonly found in the middle temporal region of the primate brain, can be utilized to analyze the patterns of retinal image motion that are generated during observer movement through the environment. The developed model determines heading by finding the peak response in a population of detectors or neurons each tuned to a particular heading direction. It is suggested that a complex interaction of multiple cell networks is required for the solution of the self-motion problem in the primate brain.
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Hyperpolarized xenon magnetic resonance of the lung and the brain
NASA Astrophysics Data System (ADS)
Venkatesh, Arvind Krishnamachari
2001-04-01
Hyperpolarized noble gas Magnetic Resonance Imaging (MRI) is a new diagnostic modality that has been used successfully for lung imaging. Xenon is soluble in blood and inhaled xenon is transported to the brain via circulating blood. Xenon also accumulates in the lipid rich white matter of the brain. Hyperpolarized xenon can hence be used as a tissue- sensitive probe of brain function. The goals of this study were to identify the NMR resonances of xenon in the rat brain and evaluate the role of hyperpolarized xenon for brain MRI. We have developed systems to produce sufficient volumes of hyperpolarized xenon for in vivo brain experiments. The specialized instrumentation developed include an apparatus for optical pump-cell manufacture and high purity gas manifolds for filling cells. A hyperpolarized gas delivery system was designed to ventilate small animals with hyperpolarized xenon for transport to the brain. The T1 of xenon dissolved in blood indicates that the lifetime of xenon in the blood is sufficient for significant magnetization to be transferred to distal tissues. A variety of carrier agents for intravenous delivery of hyperpolarized xenon were tested for transport to distal tissues. Using our new gas delivery system, high SNR 129Xe images of rat lungs were obtained. Spectroscopy with hyperpolarized xenon indicated that xenon was transported from the lungs to the blood and tissues with intact magnetization. After preliminary studies that indicated the feasibility for in vivo rat brain studies, experiments were performed with adult rats and young rats with different stages of white matter development. Both in vivo and in vitro experiments showed the prominence of one peak from xenon in the rat brain, which was assigned to brain lipids. Cerebral brain perfusion was calculated from the wash-out of the hyperpolarized xenon signal in the brain. An increase in brain perfusion during maturation was observed. These experiments showed that hyperpolarized xenon MRI can be used to develop unique approaches to studying white matter and gray matter in the brain. Some of the possible applications of hyperpolarized xenon MRI in the brain are clinical diagnosis of white matter diseases, functional MRI (fMRI) and measurement of cerebral blood perfusion.
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Remer, Justin; Croteau-Chonka, Elise; Dean, Douglas C; D'Arpino, Sara; Dirks, Holly; Whiley, Dannielle; Deoni, Sean C L
2017-06-01
Cortical maturation, including age-related changes in thickness, volume, surface area, and folding (gyrification), play a central role in developing brain function and plasticity. Further, abnormal cortical maturation is a suspected substrate in various behavioral, intellectual, and psychiatric disorders. However, in order to characterize the altered development associated with these disorders, appreciation of the normative patterns of cortical development in neurotypical children between 1 and 6 years of age, a period of peak brain development during which many behavioral and developmental disorders emerge, is necessary. To this end, we examined measures of cortical thickness, surface area, mean curvature, and gray matter volume across 34 bilateral regions in a cohort of 140 healthy children devoid of major risk factors for abnormal development. From these data, we observed linear, logarithmic, and quadratic patterns of change with age depending on brain region. Cortical thinning, ranging from 10% to 20%, was observed throughout most of the brain, with the exception of posterior brain structures, which showed initial cortical thinning from 1 to 5 years, followed by thickening. Cortical surface area expansion ranged from 20% to 108%, and cortical curvature varied by 1-20% across the investigated age range. Right-left hemisphere asymmetry was observed across development for each of the 4 cortical measures. Our results present new insight into the normative patterns of cortical development across an important but under studied developmental window, and provide a valuable reference to which trajectories observed in neurodevelopmental disorders may be compared. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Spatio-Temporal Brain Mapping of Motion-Onset VEPs Combined with fMRI and Retinotopic Maps
Pitzalis, Sabrina; Strappini, Francesca; De Gasperis, Marco; Bultrini, Alessandro; Di Russo, Francesco
2012-01-01
Neuroimaging studies have identified several motion-sensitive visual areas in the human brain, but the time course of their activation cannot be measured with these techniques. In the present study, we combined electrophysiological and neuroimaging methods (including retinotopic brain mapping) to determine the spatio-temporal profile of motion-onset visual evoked potentials for slow and fast motion stimuli and to localize its neural generators. We found that cortical activity initiates in the primary visual area (V1) for slow stimuli, peaking 100 ms after the onset of motion. Subsequently, activity in the mid-temporal motion-sensitive areas, MT+, peaked at 120 ms, followed by peaks in activity in the more dorsal area, V3A, at 160 ms and the lateral occipital complex at 180 ms. Approximately 250 ms after stimulus onset, activity fast motion stimuli was predominant in area V6 along the parieto-occipital sulcus. Finally, at 350 ms (100 ms after the motion offset) brain activity was visible again in area V1. For fast motion stimuli, the spatio-temporal brain pattern was similar, except that the first activity was detected at 70 ms in area MT+. Comparing functional magnetic resonance data for slow vs. fast motion, we found signs of slow-fast motion stimulus topography along the posterior brain in at least three cortical regions (MT+, V3A and LOR). PMID:22558222
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Brain cancer probed by native fluorescence and stokes shift spectroscopy
NASA Astrophysics Data System (ADS)
Zhou, Yan; Liu, Cheng-hui; He, Yong; Pu, Yang; Li, Qingbo; Wang, Wei; Alfano, Robert R.
2012-12-01
Optical biopsy spectroscopy was applied to diagnosis human brain cancer in vitro. The spectra of native fluorescence, Stokes shift and excitation spectra were obtained from malignant meningioma, benign, normal meningeal tissues and acoustic neuroma benign tissues. The wide excitation wavelength ranges were used to establish the criterion for distinguishing brain diseases. The alteration of fluorescence spectra between normal and abnormal brain tissues were identified by the characteristic fluorophores under the excitation with UV to visible wavelength range. It was found that the ratios of the peak intensities and peak position in both spectra of fluorescence and Stokes shift may be used to diagnose human brain meninges diseases. The preliminary analysis of fluorescence spectral data from cancer and normal meningeal tissues by basic biochemical component analysis model (BBCA) and Bayes classification model based on statistical methods revealed the changes of components, and classified the difference between cancer and normal human brain meningeal tissues in a predictions accuracy rate is 0.93 in comparison with histopathology and immunohistochemistry reports (gold standard).
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Dynamics of modularity of neural activity in the brain during development
NASA Astrophysics Data System (ADS)
Deem, Michael; Chen, Man
2014-03-01
Theory suggests that more modular systems can have better response functions at short times. This theory suggests that greater cognitive performance may be achieved for more modular neural activity, and that modularity of neural activity may, therefore, likely increase with development in children. We study the relationship between age and modularity of brain neural activity in developing children. The value of modularity calculated from fMRI data is observed to increase during childhood development and peak in young adulthood. We interpret these results as evidence of selection for plasticity in the cognitive function of the human brain. We present a model to illustrate how modularity can provide greater cognitive performance at short times and enhance fast, low-level, automatic cognitive processes. Conversely, high-level, effortful, conscious cognitive processes may not benefit from modularity. We use quasispecies theory to predict how the average modularity evolves with age, given a fitness function extracted from the model. We suggest further experiments exploring the effect of modularity on cognitive performance and suggest that modularity may be a potential biomarker for injury, rehabilitation, or disease.
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Study protocol: imaging brain development in the Childhood to Adolescence Transition Study (iCATS).
Simmons, Julian G; Whittle, Sarah L; Patton, George C; Dudgeon, Paul; Olsson, Craig; Byrne, Michelle L; Mundy, Lisa K; Seal, Marc L; Allen, Nicholas B
2014-04-30
Puberty is a critical developmental phase in physical, reproductive and socio-emotional maturation that is associated with the period of peak onset for psychopathology. Puberty also drives significant changes in brain development and function. Research to date has focused on gonadarche, driven by the hypothalamic-pituitary-gonadal axis, and yet increasing evidence suggests that the earlier pubertal stage of adrenarche, driven by the hypothalamic-pituitary-adrenal axis, may play a critical role in both brain development and increased risk for disorder. We have established a unique cohort of children who differ in their exposure to adrenarcheal hormones. This presents a unique opportunity to examine the influence of adrenarcheal timing on brain structural and functional development, and subsequent health outcomes. The primary objective of the study is to explore the hypothesis that patterns of structural and functional brain development will mediate the relationship between adrenarcheal timing and indices of affect, self-regulation, and mental health symptoms collected across time (and therefore years of development). Children were recruited based upon earlier or later timing of adrenarche, from a larger cohort, with 128 children (68 female; M age 9.51 years) and one of their parents taking part. Children completed brain MRI structural and functional sequences, provided saliva samples for adrenarcheal hormones and immune biomarkers, hair for long-term cortisol levels, and completed questionnaires, anthropometric measures and an IQ test. Parents completed questionnaires reporting on child behaviour, development, health, traumatic events, and parental report of family environment and parenting style. This study, by examining the neurobiological and behavioural consequences of relatively early and late exposure to adrenarche, has the potential to significantly impact our understanding of pubertal risk processes.
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The disposition of /sup 14/C-trimethyltin in the pregnant rat and fetus
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lipscomb, J.C.; Paule, M.G.; Slikker, W. Jr.
1989-03-01
Trimethyltin (TMT) is a potent neurotoxicant. For unknown reasons, age at exposure to TMT may dramatically influence the severity of TMT-induced neuropathology. We have demonstrated previously that radiolabel derived from (/sup 14/C)-TMT given to pregnant dams on gestational day (GD) 17 is found in fetal brain and blood. The present study was designed to determine the distribution of radiolabel derived from (14C)-TMT to brain and other tissue in fetuses from dams dosed on either GD 12 or 17 with 7.0 mg/kg TMT chloride. Radioactivity in GD 12 and GD 17 maternal whole blood peaked 1 hour after IP treatment. Wholemore » blood elimination half-lives were 12-15 days. Peak radiolabel concentrations in GD 12 maternal and fetal brain were only 11-30% of those from GD 17 animals, however, peak fetal brain concentrations of radiolabel were not different from their respective maternal brain concentrations. Radiolabel concentrations in liver, kidney, and adrenal of GD 17 dams were higher than those in corresponding GD 12 tissues. Combined urinary and fecal elimination of radiolabel for two weeks after dosing accounted for 31 and 22% of the GD 12 and 17 doses, respectively. It appears that gestational age influences the distribution and elimination of TMT in the rat.« less
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A Study of the Response of the Human Cadaver Head to Impact
Hardy, Warren N.; Mason, Matthew J.; Foster, Craig D.; Shah, Chirag S.; Kopacz, James M.; Yang, King H.; King, Albert I.; Bishop, Jennifer; Bey, Michael; Anderst, William; Tashman, Scott
2008-01-01
High-speed biplane x-ray and neutral density targets were used to examine brain displacement and deformation during impact. Relative motion, maximum principal strain, maximum shear strain, and intracranial pressure were measured in thirty-five impacts using eight human cadaver head and neck specimens. The effect of a helmet was evaluated. During impact, local brain tissue tends to keep its position and shape with respect to the inertial frame, resulting in relative motion between the brain and skull and deformation of the brain. The local brain motions tend to follow looping patterns. Similar patterns are observed for impact in different planes, with some degree of posterior-anterior and right-left symmetry. Peak coup pressure and pressure rate increase with increasing linear acceleration, but coup pressure pulse duration decreases. Peak average maximum principal strain and maximum shear are on the order of 0.09 for CFC 60 Hz data for these tests. Peak average maximum principal strain and maximum shear increase with increasing linear acceleration, coup pressure, and coup pressure rate. Linear and angular acceleration of the head are reduced with use of a helmet, but strain increases. These results can be used for the validation of finite element models of the human head. PMID:18278591
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Impact of mild traumatic brain injury on auditory brain stem dysfunction in mouse model.
Amanipour, Reza M; Frisina, Robert D; Cresoe, Samantha A; Parsons, Teresa J; Xiaoxia Zhu; Borlongan, Cesario V; Walton, Joseph P
2016-08-01
The auditory brainstem response (ABR) is an electrophysiological test that examines the functionality of the auditory nerve and brainstem. Traumatic brain injury (TBI) can be detected if prolonged peak latency is observed in ABR measurements, since latency measures the neural conduction time in the brainstem, and an increase in latency can be a sign of pathological lesion at the auditory brainstem level. The ABR is elicited by brief sounds that can be used to measure hearing sensitivity as well as temporal processing. Reduction in peak amplitudes and increases in latency are indicative of dysfunction in the auditory nerve and/or central auditory pathways. In this study we used sixteen young adult mice that were divided into two groups: sham and mild traumatic brain injury (mTBI), with ABR measurements obtained prior to, and at 2, 6, and 14 weeks after injury. Abnormal ABRs were observed for the nine TBI cases as early as two weeks after injury and the deficits lasted for fourteen weeks after injury. Results indicated a significant reduction in the Peak 1 (P1) and Peak 4 (P4) amplitudes to the first noise burst, as well as an increase in latency response for P1 and P4 following mTBI. These results are the first to demonstrate auditory sound processing deficits in a rodent model of mild TBI.
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The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus.
Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong; Clokie, Samuel J; Zykovich, Artem; Coon, Steven L; Klein, David C; Rath, Martin F
2015-01-01
Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9(-/-) mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9(-/-) mutant mice appear normal, severe hydrocephalus develops in about 70% of the Lhx9(-/-) mice at 5-8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9(-/-)mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus.
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The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus
Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong; Clokie, Samuel J.; Zykovich, Artem; Coon, Steven L.; Klein, David C.; Rath, Martin F.
2014-01-01
Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9−/− mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9−/− mutant mice appear normal, severe hydrocephalus develops in about 70 % of the Lhx9−/− mice at 5–8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9−/−mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus. PMID:24647753
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Hua, Chiaho; Wu, Shengjie; Chemaitilly, Wassim; Lukose, Renin C; Merchant, Thomas E
2012-11-15
To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n=72), low-grade glioma (n=28) or craniopharyngioma (n=6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test≥7 ng/mL. Independent predictor variables identified by multivariate logistic regression with high statistical significance (p<0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency. Copyright © 2012 Elsevier Inc. All rights reserved.
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Sharma, Hari S.; Kiyatkin, Eugene A.
2009-01-01
This study describes morphological abnormalities of brain cells during acute methamphetamine (METH) intoxication in the rat and demonstrates the role of hyperthermia, disruption of the blood-brain barrier (BBB) and edema in their development. Rats with chronically implanted brain, muscle and skin temperature probes and an intravenous (iv) catheter were exposed to METH (9 mg/kg) at standard (23°C) and warm (29°C) ambient temperatures, allowing for the observation of hyperthermia ranging from mild to pathological levels (38–42°C). When brain temperature peaked or reached a level suggestive of possible lethality (>41.5°C), rats were injected with Evans blue (EB), rapidly anesthetized, perfused, and their brains were taken for further analyses. Four brain areas (cortex, hippocampus, thalamus and hypothalamus) were analyzed for EB extravasation, water and electrolyte (Na+, K+, Cl−) contents, immunostained for albumin and glial fibrillary acidic protein, and examined for neuronal, glial and axonal alterations using standard light and electron microscopy. These examinations revealed profound abnormalities in neuronal, glial, and endothelial cells, which were stronger with METH administered at 29°C than 23°C and tightly correlated with brain and body hyperthermia. These changes had some structural specificity, but in each structure they tightly correlated with increases in EB levels, the numbers of albumin-positive cells, and water and ion contents, suggesting leakage of the BBB, acutely developing brain edema, and serious shifts in brain ion homeostasis as leading factors underlying brain abnormalities. While most of these acute structural and functional abnormalities appear to be reversible, they could trigger subsequent cellular alterations in the brain and accelerate neurodegeneration—the most dangerous complication of chronic amphetamine-like drug abuse. PMID:18773954
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Xenon Protects against Blast-Induced Traumatic Brain Injury in an In Vitro Model.
Campos-Pires, Rita; Koziakova, Mariia; Yonis, Amina; Pau, Ashni; Macdonald, Warren; Harris, Katie; Edge, Christopher J; Franks, Nicholas P; Mahoney, Peter F; Dickinson, Robert
2018-04-15
The aim of this study was to evaluate the neuroprotective efficacy of the inert gas xenon as a treatment for patients with blast-induced traumatic brain injury in an in vitro laboratory model. We developed a novel blast traumatic brain injury model using C57BL/6N mouse organotypic hippocampal brain-slice cultures exposed to a single shockwave, with the resulting injury quantified using propidium iodide fluorescence. A shock tube blast generator was used to simulate open field explosive blast shockwaves, modeled by the Friedlander waveform. Exposure to blast shockwave resulted in significant (p < 0.01) injury that increased with peak-overpressure and impulse of the shockwave, and which exhibited a secondary injury development up to 72 h after trauma. Blast-induced propidium iodide fluorescence overlapped with cleaved caspase-3 immunofluorescence, indicating that shock-wave-induced cell death involves apoptosis. Xenon (50% atm) applied 1 h after blast exposure reduced injury 24 h (p < 0.01), 48 h (p < 0.05), and 72 h (p < 0.001) later, compared with untreated control injury. Xenon-treated injured slices were not significantly different from uninjured sham slices at 24 h and 72 h. We demonstrate for the first time that xenon treatment after blast traumatic brain injury reduces initial injury and prevents subsequent injury development in vitro. Our findings support the idea that xenon may be a potential first-line treatment for those with blast-induced traumatic brain injury.
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Six Degree-of-Freedom Measurements of Human Mild Traumatic Brain Injury.
Hernandez, Fidel; Wu, Lyndia C; Yip, Michael C; Laksari, Kaveh; Hoffman, Andrew R; Lopez, Jaime R; Grant, Gerald A; Kleiven, Svein; Camarillo, David B
2015-08-01
This preliminary study investigated whether direct measurement of head rotation improves prediction of mild traumatic brain injury (mTBI). Although many studies have implicated rotation as a primary cause of mTBI, regulatory safety standards use 3 degree-of-freedom (3DOF) translation-only kinematic criteria to predict injury. Direct 6DOF measurements of human head rotation (3DOF) and translation (3DOF) have not been previously available to examine whether additional DOFs improve injury prediction. We measured head impacts in American football, boxing, and mixed martial arts using 6DOF instrumented mouthguards, and predicted clinician-diagnosed injury using 12 existing kinematic criteria and 6 existing brain finite element (FE) criteria. Among 513 measured impacts were the first two 6DOF measurements of clinically diagnosed mTBI. For this dataset, 6DOF criteria were the most predictive of injury, more than 3DOF translation-only and 3DOF rotation-only criteria. Peak principal strain in the corpus callosum, a 6DOF FE criteria, was the strongest predictor, followed by two criteria that included rotation measurements, peak rotational acceleration magnitude and Head Impact Power (HIP). These results suggest head rotation measurements may improve injury prediction. However, more 6DOF data is needed to confirm this evaluation of existing injury criteria, and to develop new criteria that considers directional sensitivity to injury.
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Selective alignment of brain responses by task demands during semantic processing.
Baggio, Giosuè
2012-04-01
The way the brain binds together words to form sentences may depend on whether and how the arising cognitive representation is to be used in behavior. The amplitude of the N400 effect in event-related brain potentials is inversely correlated with the degree of fit of a word's meaning into a semantic representation of the preceding discourse. This study reports a double dissociation in the latency characteristics of the N400 effect depending on task demands. When participants silently read words in a sentence context, without issuing a relevant overt response, greater temporal alignment over recording sites occurs for N400 onsets than peaks. If however a behavior is produced - here pressing a button in a binary probe selection task - exactly the opposite pattern is observed, with stronger alignment of N400 peaks than onsets. The peak amplitude of the N400 effect correlates best with the latency characteristic showing less temporal dispersion. These findings suggest that meaning construction in the brain is subtly affected by task demands, and that there is complex functional integration between semantic combinatorics and control systems handling behavioral goals. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Noninvasive, localized, and transient brain drug delivery using focused ultrasound and microbubbles
NASA Astrophysics Data System (ADS)
Choi, James J.
In the United States, Alzheimer's disease (AD), Parkinson's disease (PD), and brain cancer caused 72,432, 19,566 and 12,886 deaths in 2006, respectively. Whereas the number of deaths due to major disorders such as heart disease, stroke, and prostate cancer have decreased since 2006, deaths attributed to AD, PD, and brain cancer have not. Treatment options for patients with CNS disorders remain limited despite significant advances in knowledge of CNS disease pathways and development of neurologically potent agents. One of the major obstacles is that the cerebral microvasculature is lined by a specialized and highly regulated blood-brain barrier (BBB) that prevents large agents from entering the brain extracellular space. The purpose of this dissertation is to design a noninvasive, localized, and transient BBB opening system using focused ultrasound (FUS) and determine ultrasound and microbubble conditions that can effectively and safely deliver large pharmacologically-relevant-sized agents to the brain. To meet this end, an in vivo mouse brain drug delivery system using a stereotactic-based targeting method was developed. FUS was applied noninvasively through the intact skin and skull, which allowed for long-term and high-throughput studies. With this system, more than 150 mice were exposed to one of 31 distinct acoustic and microbubble conditions. The feasibility of delivering a large MRI contrast agent was first demonstrated in vivo in both wild-type and transgenic Alzheimer's disease model (APP/PS1) mice. A wide range of acoustic and microbubble conditions were then evaluated for their ability to deliver agents to a target region. Interestingly, the possible design space of parameters was found to be vast and different conditions resulted in distinct spatial distributions and doses delivered. In particular, BBB opening was shown to be dependent on the microbubble diameter, acoustic pressure, pulse repetition frequency (PRF), and pulse length (PL). Each set of conditions determined both the size of agents that can traverse the BBB, and also the level of safety of the technique. In one set of conditions (peak-rarefactional pressure: 0.61 MPa, PRF: 10 Hz, PL: 20 ms), large 70-kDa dextran was delivered to a target region, but were associated with detectable damaged sites as indicated by dark neurons, microvacuolations, and erythrocyte extravasations. Another set of conditions (peak-rarefactional pressure: 0.46 MPa, PRF: 5 Hz, PL: 0.2 ms) delivered 3-kDa dextran homogeneously and diffusely to a target region in the brain without any detectable dark neurons, microvacuolations, or erythrocyte extravasations. Each distinct set of conditions may thus be used for different clinical application, i.e., treatment of brain cancer and AD. In conclusion, an effective method to noninvasively, locally, and transiently deliver large therapeutic agents through the BBB was developed.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Gompers, Andrea L.; Su-Feher, Linda; Ellegood, Jacob
The chromatin remodeling gene CHD8 represents a central node in neurodevelopmental gene networks implicated in autism. In this paper, we examined the impact of germline heterozygous frameshift Chd8 mutation on neurodevelopment in mice. Chd8 +/ del5 mice displayed normal social interactions with no repetitive behaviors but exhibited cognitive impairment correlated with increased regional brain volume, validating that phenotypes of Chd8 +/ del5 mice overlap pathology reported in humans with CHD8 mutations. We applied network analysis to characterize neurodevelopmental gene expression, revealing widespread transcriptional changes in Chd8 +/ del5 mice across pathways disrupted in neurodevelopmental disorders, including neurogenesis, synaptic processes andmore » neuroimmune signaling. We identified a co-expression module with peak expression in early brain development featuring dysregulation of RNA processing, chromatin remodeling and cell-cycle genes enriched for promoter binding by Chd8, and we validated increased neuronal proliferation and developmental splicing perturbation in Chd8 +/ del5 mice. Finally, this integrative analysis offers an initial picture of the consequences of Chd8 haploinsufficiency for brain development.« less
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Mammals have a marked period of rapid brain growth and development (BGS), which is postnatal in mice and rats, spanning the first 3-4 weeks of life and reaching its peak around postnatal day 10. CaMKII, GAP-43 and BDNF play important roles during the BGS in mammals. One class of ...
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ERIC Educational Resources Information Center
Drury, Stacy S.
2009-01-01
Dr. Jay Giedd says that the main alterations in the adolescent brain are the inverted U-shaped developmental trajectories with late childhood/early teen peaks for gray matter volume among others. Giedd adds that the adolescent brain is vulnerable to substances that artificially modulate dopamine levels since its reward system is in a state of flux.
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Shin, Yong Beom; Kim, Seong-Jang; Kim, In-Ju; Kim, Yong-Ki; Kim, Dong-Soo; Park, Jae Heung; Yeom, Seok-Ran
2006-06-01
Statistical parametric mapping (SPM) was applied to brain perfusion single photon emission computed tomography (SPECT) images in patients with traumatic brain injury (TBI) to investigate regional cerebral abnormalities compared to age-matched normal controls. Thirteen patients with TBI underwent brain perfusion SPECT were included in this study (10 males, three females, mean age 39.8 +/- 18.2, range 21 - 74). SPM2 software implemented in MATLAB 5.3 was used for spatial pre-processing and analysis and to determine the quantitative differences between TBI patients and age-matched normal controls. Three large voxel clusters of significantly decreased cerebral blood perfusion were found in patients with TBI. The largest clusters were area including medial frontal gyrus (voxel number 3642, peak Z-value = 4.31, 4.27, p = 0.000) in both hemispheres. The second largest clusters were areas including cingulated gyrus and anterior cingulate gyrus of left hemisphere (voxel number 381, peak Z-value = 3.67, 3.62, p = 0.000). Other clusters were parahippocampal gyrus (voxel number 173, peak Z-value = 3.40, p = 0.000) and hippocampus (voxel number 173, peak Z-value = 3.23, p = 0.001) in the left hemisphere. The false discovery rate (FDR) was less than 0.04. From this study, group and individual analyses of SPM2 could clearly identify the perfusion abnormalities of brain SPECT in patients with TBI. Group analysis of SPM2 showed hypoperfusion pattern in the areas including medial frontal gyrus of both hemispheres, cingulate gyrus, anterior cingulate gyrus, parahippocampal gyrus and hippocampus in the left hemisphere compared to age-matched normal controls. Also, left parahippocampal gyrus and left hippocampus were additional hypoperfusion areas. However, these findings deserve further investigation on a larger number of patients to be performed to allow a better validation of objective SPM analysis in patients with TBI.
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SU-F-T-673: Effects of Cardiac Induced Brain Pulsations On Proton Minibeams
DOE Office of Scientific and Technical Information (OSTI.GOV)
Eagle, J; Marsh, S; Lee, E
Purpose: To quantify the dosimetric impact of internal motion within the brain on spatially modulated proton minibeam radiation therapy (pMRT) for small animal research. Methods: The peak-to-valley dose ratio (PVDR) is an essential dosimetric factor for pMRT. Motion of an animal brain caused by cardiac-induced pulsations (CIP) can impact dose deposition. For synchrotron generated high dose rate X-ray microbeams this effect is evaded due to the quasi-instantaneous delivery. By comparison, pMRT potentially suffers increased spread due to lower dose rates. However, for a given dose rate it is less susceptible to beam spread than microbeams, due to the spatial modulationmore » being an order of magnitude larger. Monte Carlo simulations in TOPAS were used to model the beam spread for a 50.5MeV pMRT beam. Motion effects were simulated for a 50mm thick brass collimator with 0.3mm slit width and 1.0mm center-to-center spacing in a water phantom. The maximum motion in a rat brain due to CIP has been reported to be 0.06mm. Motion was simulated with a peak amplitude in the range 0–0.2mm. Results: The impact of 0.06mm peak motion was minimal and reduced the PVDR by about 1% at a depth of 10mm. For 0.2mm peak motion the PVDR was reduced by 16% at a depth of 10mm. Conclusion: For the pMRT beam the magnitude of cardiac-induced brain motion has minimal impact on the PVDR for the investigated collimator geometry. For more narrow beams the effect is likely to be larger. This indicates that delivery of pMRT to small animal brains should not be affected considerably by beamlines with linac compatible dose rates.« less
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Takmakov, Pavel; Zachek, Matthew K.; Keithley, Richard B.; Bucher, Elizabeth; McCarty, Gregory S.; Wightman, R. Mark
2010-01-01
Transient local pH changes in the brain are important markers of neural activity that can be used to follow metabolic processes that underlie the biological basis of behavior, learning and memory. There are few methods that can measure pH fluctuations with sufficient time resolution in freely moving animals. Previously, fast-scan cyclic voltammetry at carbon-fiber microelectrodes was used for the measurement of such pH transients. However, the origin of the potential dependent current in the cyclic voltammograms for pH changes recorded in vivo was unclear. The current work explored the nature of these peaks and established the origin for some of them. A peak relating to the capacitive nature of the pH CV was identified. Adsorption of electrochemically inert species, such as aromatic amines and calcium could suppress this peak, and is the origin for inconsistencies regarding in vivo and in vitro data. Also, we identified an extra peak in the in vivo pH CV relating to the presence of 3,4-dihydroxyacetic acid (DOPAC) in the brain extracellular fluid. To evaluate the in vivo performance of the carbon-fiber sensor, carbon dioxide inhalation by an anesthetized rat was used to induce brain acidosis induced by hypercapnia. Hypercapnia is demonstrated to be a useful tool to induce robust in vivo pH changes, allowing confirmation of the pH signal observed with FSCV. PMID:21047096
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Roland, Dominique; Jissendi-Tchofo, Patrice; Briand, Gilbert; Vamecq, Joseph; Fontaine, Monique; Ultré, Vincent; Acquaviva-Bourdain, Cécile; Mention, Karine; Dobbelaere, Dries
2017-06-01
3-Hydroxy-3-Methylglutaryl-Coenzyme A (HMG-CoA) lyase deficiency is a rare inborn error of leucine metabolism and ketogenesis. Despite recurrent hypoglycemia and metabolic decompensations, most patients have a good clinical and neurological outcome contrasting with abnormal brain magnetic resonance imaging (MRI) signals and consistent abnormal brain proton magnetic resonance spectroscopy ( 1 H-MRS) metabolite peaks. Identifying these metabolites could provide surrogate markers of the disease and improve understanding of MRI-clinical discrepancy and follow-up of affected patients. Urine samples, brain MRI and 1 H-MRS in 5 patients with HMG-CoA lyase deficiency (4 boys and 1 girl aged from 25days to 10years) were, for each patient, obtained on the same day. Brain and urine spectroscopy were performed at the same pH by studying urine at pH 7.4. Due to pH-induced modifications in chemical shifts and because reference 1 H NMR spectra are obtained at pH 2.5, spectroscopy of normal urine added with the suspected metabolite was further performed at this pH to validate the correct identification of compounds. Mild to extended abnormal white matter MRI signals were observed in all cases. Brain spectroscopy abnormal peaks at 0.8-1.1ppm, 1.2-1.4ppm and 2.4ppm were also detected by urine spectroscopy at pH 7.4. Taking into account pH-induced changes in chemical shifts, brain abnormal peaks in patients were formally identified to be those of 3-hydroxyisovaleric, 3-methylglutaconic, 3-methylglutaric and 3-hydroxy-3-methylglutaric acids. 3-Methylglutaric, 3-hydroxyisovaleric and 3-hydroxy-3-methylglutaric acids identified on urine 1 H-NMR spectra of 5 patients with HMG-CoA lyase deficiency are responsible for the cerebral spectroscopy signature seen in these patients, validating their local involvement in brain and putative contribution to brain neuropathology. Copyright © 2017 Elsevier Inc. All rights reserved.
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Zhong, Suyu; He, Yong; Shu, Hua; Gong, Gaolang
2017-04-01
Human brain asymmetries have been well described. Intriguingly, a number of asymmetries in brain phenotypes have been shown to change throughout the lifespan. Recent studies have revealed topological asymmetries between hemispheric white matter networks in the human brain. However, it remains unknown whether and how these topological asymmetries evolve from adolescence to young adulthood, a critical period that constitutes the second peak of human brain and cognitive development. To address this question, the present study included a large cohort of healthy adolescents and young adults. Diffusion and structural magnetic resonance imaging were acquired to construct hemispheric white matter networks, and graph-theory was applied to quantify topological parameters of the hemispheric networks. In both adolescents and young adults, rightward asymmetry in both global and local network efficiencies was consistently observed between the 2 hemispheres, but the degree of the asymmetry was significantly decreased in young adults. At the nodal level, the young adults exhibited less rightward asymmetry of nodal efficiency mainly around the parasylvian area, posterior tempo-parietal cortex, and fusiform gyrus. These developmental patterns of network asymmetry provide novel insight into the human brain structural development from adolescence to young adulthood and also likely relate to the maturation of language and social cognition that takes place during this period. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Liu, Yuhui; Liu, Xibin; Xu, Liang; Liu, Liheng; Sun, Yuhong; Li, Minghuan; Zeng, Haiyan; Yuan, Shuanghu; Yu, Jinming
2018-05-17
This study used magnetic resonance imaging (MRI) to monitor changes to brain metastases and investigate the imaging signs used to evaluate treatment efficacy and determine prognosis following radiotherapy for brain metastases from lung cancer. A total of 60 non-small cell lung cancer patients with brain oligometastases were selected. MRI scans were conducted before and 3, 6, 9, 12, 18, 24, and 30 months after radiotherapy. The tumor and peritumoral edema diameters, Cho/Cr values, elevation of the Lip peak value, and whether the island (yu-yuan) sign or high-signal ring were present on T2 fluid-attenuated inversion recovery (FLAIR) imaging were recorded for each metastasis. The mortality risk was higher the earlier the maximum value of peritumoral edema diameter was reached, when there were fewer island signs, and when brain metastases did not present as tumor progression on imaging. There were significant differences in the average peritumoral edema diameter, apparent diffusion coefficient value, the number of elevated Lip peak values, and the number of T2 FLAIR imaging high-signal rings in a year after radiotherapy in 14 patients with a survival period < 1 year compared to patients with a survival period > 2 years. After radiotherapy for brain metastases, patients with the island sign had longer survival periods, high-signal rings in T2 FLAIR, elevated Lip peaks, and reduced apparent diffusion coefficient values, indicating tumor necrosis. Increased diameter of metastases and Cho/Cr > 2 cannot serve as reliable indicators of brain metastasis progression. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
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Cardiorespiratory fitness, cognition and brain structure after TIA or minor ischemic stroke.
Boss, H Myrthe; Van Schaik, Sander M; Witkamp, Theo D; Geerlings, Mirjam I; Weinstein, Henry C; Van den Berg-Vos, Renske M
2017-10-01
Background It is not known whether cardiorespiratory fitness is associated with better cognitive performance and brain structure in patients with a TIA or minor ischemic stroke. Aims To examine the association between cardiorespiratory fitness, cognition and brain structure in patients with a TIA and minor stroke. Methods The study population consisted of patients with a TIA or minor stroke with a baseline measurement of the peak oxygen consumption, a MRI scan of brain and neuropsychological assessment. Composite z-scores were calculated for the cognitive domains attention, memory and executive functioning. White matter hyperintensities, microbleeds and lacunes were rated visually. The mean apparent diffusion coefficient was measured in regions of interest in frontal and occipital white matter and in the centrum semiovale as a marker of white matter structure. Normalized brain volumes were estimated by use of Statistical Parametric Mapping. Results In 84 included patients, linear regression analysis adjusted for age, sex and education showed that a higher peak oxygen consumption was associated with higher cognitive z-scores, a larger grey matter volume (B = 0.15 (95% CI 0.05; 0.26)) and a lower mean apparent diffusion coefficient (B = -.004 (95% CI -.007; -.001)). We found no association between the peak oxygen consumption and severe white matter hyperintensities, microbleeds, lacunes and total brain volume. Conclusions These data suggest that cardiorespiratory fitness is associated with better cognitive performance, greater grey matter volume and greater integrity of the white matter in patients with a TIA or minor ischemic stroke. Further prospective trials are necessary to define the effect of cardiorespiratory fitness on cognition and brain structure in patients with TIA or minor stroke.
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A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia.
Skene, Nathan G; Roy, Marcia; Grant, Seth Gn
2017-09-12
The genetic mechanisms regulating the brain and behaviour across the lifespan are poorly understood. We found that lifespan transcriptome trajectories describe a calendar of gene regulatory events in the brain of humans and mice. Transcriptome trajectories defined a sequence of gene expression changes in neuronal, glial and endothelial cell-types, which enabled prediction of age from tissue samples. A major lifespan landmark was the peak change in trajectories occurring in humans at 26 years and in mice at 5 months of age. This species-conserved peak was delayed in females and marked a reorganization of expression of synaptic and schizophrenia-susceptibility genes. The lifespan calendar predicted the characteristic age of onset in young adults and sex differences in schizophrenia. We propose a genomic program generates a lifespan calendar of gene regulation that times age-dependent molecular organization of the brain and mutations that interrupt the program in young adults cause schizophrenia.
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Beyond stereotypes of adolescent risk taking: Placing the adolescent brain in developmental context☆
Romer, Daniel; Reyna, Valerie F.; Satterthwaite, Theodore D.
2017-01-01
Recent neuroscience models of adolescent brain development attribute the morbidity and mortality of this period to structural and functional imbalances between more fully developed limbic regions that subserve reward and emotion as opposed to those that enable cognitive control. We challenge this interpretation of adolescent development by distinguishing risk-taking that peaks during adolescence (sensation seeking and impulsive action) from risk taking that declines monotonically from childhood to adulthood (impulsive choice and other decisions under known risk). Sensation seeking is primarily motivated by exploration of the environment under ambiguous risk contexts, while impulsive action, which is likely to be maladaptive, is more characteristic of a subset of youth with weak control over limbic motivation. Risk taking that declines monotonically from childhood to adulthood occurs primarily under conditions of known risks and reflects increases in executive function as well as aversion to risk based on increases in gist-based reasoning. We propose an alternative Lifespan Wisdom Model that highlights the importance of experience gained through exploration during adolescence. We propose, therefore, that brain models that recognize the adaptive roles that cognition and experience play during adolescence provide a more complete and helpful picture of this period of development. PMID:28777995
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Influence of angular acceleration-deceleration pulse shapes on regional brain strains.
Yoganandan, Narayan; Li, Jianrong; Zhang, Jiangyue; Pintar, Frank A; Gennarelli, Thomas A
2008-07-19
Recognizing the association of angular loading with brain injuries and inconsistency in previous studies in the application of the biphasic loads to animal, physical, and experimental models, the present study examined the role of the acceleration-deceleration pulse shapes on region-specific strains. An experimentally validated two-dimensional finite element model representing the adult male human head was used. The model simulated the skull and falx as a linear elastic material, cerebrospinal fluid as a hydrodynamic material, and cerebrum as a linear viscoelastic material. The angular loading matrix consisted coronal plane rotation about a center of rotation that was acceleration-only (4.5 ms duration, 7.8 krad/s/s peak), deceleration-only (20 ms, 1.4 krad/s/s peak), acceleration-deceleration, and deceleration-acceleration pulses. Both biphasic pulses had peaks separated by intervals ranging from 0 to 25 ms. Principal strains were determined at the corpus callosum, base of the postcentral sulcus, and cerebral cortex of the parietal lobe. The cerebrum was divided into 17 regions and peak values of average maximum principal strains were determined. In all simulations, the corpus callosum responded with the highest strains. Strains were the least under all simulations in the lower parietal lobes. In all regions peak strains were the same for both monophase pulses suggesting that the angular velocity may be a better metric than peak acceleration or deceleration. In contrast, for the biphasic pulse, peak strains were region- and pulse-shape specific. Peak values were lower in both biphasic pulses when there was no time separation between the pulses than the corresponding monophase pulse. Increasing separation time intervals increased strains, albeit non-uniformly. Acceleration followed by deceleration pulse produced greater strains in all regions than the other form of biphasic pulse. Thus, pulse shape appears to have an effect on regional strains in the brain.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org; Wu Shengjie; Chemaitilly, Wassim
Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6),more » who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.« less
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Solubilization and purification of melatonin receptors from lizard brain.
Rivkees, S A; Conron, R W; Reppert, S M
1990-09-01
Melatonin receptors in lizard brain were identified and characterized using 125I-labeled melatonin ([125I]MEL) after solubilization with the detergent digitonin. Saturation studies of solubilized material revealed a high affinity binding site, with an apparent equilibrium dissociation constant of 181 +/- 45 pM. Binding was reversible and inhibited by melatonin and closely related analogs, but not by serotonin or norepinephrine. Treatment of solubilized material with the non-hydrolyzable GTP analog, guanosine 5'-(3-O-thiotriphosphate) (GTP-gamma-S), significantly reduced receptor affinity. Gel filtration chromatography of solubilized melatonin receptors revealed a high affinity, large (Mr 400,000) peak of specific binding. Pretreatment with GTP-gamma-S before solubilization resulted in elution of a lower affinity, smaller (Mr 150,000) peak of specific binding. To purify solubilized receptors, a novel affinity chromatography resin was developed by coupling 6-hydroxymelatonin with Epoxy-activated Sepharose 6B. Using this resin, melatonin receptors were purified approximately 10,000-fold. Purified material retained the pharmacologic specificity of melatonin receptors. These results show that melatonin receptors that bind ligand after detergent treatment can be solubilized and substantially purified by affinity chromatography.
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Magnetic resonance imaging spectroscopy in pediatric atypical teratoid rhabdoid tumors of the brain.
Bruggers, Carol S; Moore, Kevin
2014-08-01
Pediatric central nervous system (CNS) atypical teratoid rhabdoid tumors (ATRT) are highly malignant tumors characterized by SMARCB1 gene abnormalities. Despite chemoradiation responsiveness, most children die of disease. No imaging findings distinguish ATRT from other malignant brain tumors. This study sought to describe magnetic resonance spectroscopy (MRS) of childhood CNS ATRT and identify metabolite patterns for diagnosis and disease status monitoring. Data from 7 children diagnosed with CNS ATRT from 2007 to 2010, whose imaging included MRS, were retrospectively reviewed. Age at diagnosis ranged from 2.5 to 54 months. Tumors were large with calcium and cysts and avid gadolinium enhancement. All were isointense on T1-weighted imaging and mildly hyperintense on T2-weighted imaging. Short-TE MRS showed prominent lactate+lipid and choline, minimal N-acetyl acetate (NAA), and rarely minimal myoinositol and low creatine peaks. Long TE showed prominent choline, minimal NAA, and rarely low lactate peaks. The combination of prominent choline and lactate+lipids peaks, and generally absent NAA and myoinositol peaks by MRS in this panel of ATRT expands existing information and provides a potentially distinct metabolite profile from other malignant pediatric brain tumors, including medulloblastoma. Prospective, comparative quantitative MRS of ATRT with other pediatric CNS tumors is warranted.
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Permanent hypopituitarism is rare after structural traumatic brain injury in early childhood.
Heather, Natasha L; Jefferies, Craig; Hofman, Paul L; Derraik, José G B; Brennan, Christine; Kelly, Patrick; Hamill, James K M; Jones, Rhys G; Rowe, Deborah L; Cutfield, Wayne S
2012-02-01
We sought to determine the incidence of permanent hypopituitarism in a potentially high-risk group: young children after structural traumatic brain injury (TBI). We conducted a cross-sectional study with longitudinal follow-up. Dynamic tests of pituitary function (GH and ACTH) were performed in all subjects and potential abnormalities critically evaluated. Puberty was clinically staged; baseline thyroid function, prolactin, IGF-I, serum sodium, and osmolality were compared with age-matched data. Diagnosis of GH deficiency was based on an integrated assessment of stimulated GH peak (<5 μg/liter suggestive of deficiency), IGF-I, and growth pattern. ACTH deficiency was diagnosed based on a subnormal response to two serial Synacthen tests (peak cortisol <500 nmol/liter) and a metyrapone test. We studied 198 survivors of structural TBI sustained in early childhood (112 male, age at injury 1.7 ± 1.5 yr) 6.5 ± 3.2 yr after injury. Sixty-four of the injuries (33%) were inflicted and 134 (68%) accidental. Two participants had developed precocious puberty, which is within the expected background population rate. Peak stimulated GH was subnormal in 16 participants (8%), in the context of normal IGF-I and normal growth. Stimulated peak cortisol was low in 17 (8%), but all had normal ACTH function on follow-up. One participant had a transient low serum T(4). Therefore, no cases of hypopituitarism were recorded. Permanent hypopituitarism is rare after both inflicted and accidental structural TBI in early childhood. Precocious puberty was the only pituitary hormone abnormality found, but the prevalence did not exceed that of the normal population.
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Xenon Protects against Blast-Induced Traumatic Brain Injury in an In Vitro Model
Campos-Pires, Rita; Koziakova, Mariia; Yonis, Amina; Pau, Ashni; Macdonald, Warren; Harris, Katie; Edge, Christopher J.; Franks, Nicholas P.; Mahoney, Peter F.
2018-01-01
Abstract The aim of this study was to evaluate the neuroprotective efficacy of the inert gas xenon as a treatment for patients with blast-induced traumatic brain injury in an in vitro laboratory model. We developed a novel blast traumatic brain injury model using C57BL/6N mouse organotypic hippocampal brain-slice cultures exposed to a single shockwave, with the resulting injury quantified using propidium iodide fluorescence. A shock tube blast generator was used to simulate open field explosive blast shockwaves, modeled by the Friedlander waveform. Exposure to blast shockwave resulted in significant (p < 0.01) injury that increased with peak-overpressure and impulse of the shockwave, and which exhibited a secondary injury development up to 72 h after trauma. Blast-induced propidium iodide fluorescence overlapped with cleaved caspase-3 immunofluorescence, indicating that shock-wave–induced cell death involves apoptosis. Xenon (50% atm) applied 1 h after blast exposure reduced injury 24 h (p < 0.01), 48 h (p < 0.05), and 72 h (p < 0.001) later, compared with untreated control injury. Xenon-treated injured slices were not significantly different from uninjured sham slices at 24 h and 72 h. We demonstrate for the first time that xenon treatment after blast traumatic brain injury reduces initial injury and prevents subsequent injury development in vitro. Our findings support the idea that xenon may be a potential first-line treatment for those with blast-induced traumatic brain injury. PMID:29285980
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Construction and comparative evaluation of different activity detection methods in brain FDG-PET.
Buchholz, Hans-Georg; Wenzel, Fabian; Gartenschläger, Martin; Thiele, Frank; Young, Stewart; Reuss, Stefan; Schreckenberger, Mathias
2015-08-18
We constructed and evaluated reference brain FDG-PET databases for usage by three software programs (Computer-aided diagnosis for dementia (CAD4D), Statistical Parametric Mapping (SPM) and NEUROSTAT), which allow a user-independent detection of dementia-related hypometabolism in patients' brain FDG-PET. Thirty-seven healthy volunteers were scanned in order to construct brain FDG reference databases, which reflect the normal, age-dependent glucose consumption in human brain, using either software. Databases were compared to each other to assess the impact of different stereotactic normalization algorithms used by either software package. In addition, performance of the new reference databases in the detection of altered glucose consumption in the brains of patients was evaluated by calculating statistical maps of regional hypometabolism in FDG-PET of 20 patients with confirmed Alzheimer's dementia (AD) and of 10 non-AD patients. Extent (hypometabolic volume referred to as cluster size) and magnitude (peak z-score) of detected hypometabolism was statistically analyzed. Differences between the reference databases built by CAD4D, SPM or NEUROSTAT were observed. Due to the different normalization methods, altered spatial FDG patterns were found. When analyzing patient data with the reference databases created using CAD4D, SPM or NEUROSTAT, similar characteristic clusters of hypometabolism in the same brain regions were found in the AD group with either software. However, larger z-scores were observed with CAD4D and NEUROSTAT than those reported by SPM. Better concordance with CAD4D and NEUROSTAT was achieved using the spatially normalized images of SPM and an independent z-score calculation. The three software packages identified the peak z-scores in the same brain region in 11 of 20 AD cases, and there was concordance between CAD4D and SPM in 16 AD subjects. The clinical evaluation of brain FDG-PET of 20 AD patients with either CAD4D-, SPM- or NEUROSTAT-generated databases from an identical reference dataset showed similar patterns of hypometabolism in the brain regions known to be involved in AD. The extent of hypometabolism and peak z-score appeared to be influenced by the calculation method used in each software package rather than by different spatial normalization parameters.
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Breuer, Heike; Leiter, Ina; Märkel, Martin; Bascuñana, Pablo; Michalski, Dominik; Bengel, Frank M.; Löscher, Wolfgang; Meier, Martin; Bankstahl, Jens P.; Härtig, Wolfgang
2018-01-01
Abstract Increased permeability of the blood–brain barrier (BBB) following cerebral injury results in regional extravasation of plasma proteins and can critically contribute to the pathogenesis of epilepsy. Here, we comprehensively explore the spatiotemporal evolution of a main extravasation component, albumin, and illuminate associated responses of the neurovascular unit (NVU) contributing to early epileptogenic neuropathology. We applied translational in vivo MR imaging and complementary immunohistochemical analyses in the widely used rat pilocarpine post–status epilepticus (SE) model. The observed rapid BBB leakage affected major epileptogenesis-associated brain regions, peaked between 1 and 2 d post-SE, and rapidly declined thereafter, accompanied by cerebral edema generally following the same time course. At peak of BBB leakage, serum albumin colocalized with NVU constituents, such as vascular components, neurons, and brain immune cells. Surprisingly, astroglial markers did not colocalize with albumin, and aquaporin-4 (AQP4) was clearly reduced in areas of leaky BBB, indicating a severe disturbance of astrocyte-mediated endothelial-neuronal coupling. In addition, a distinct adaptive reorganization process of the NVU vasculature apparently takes place at sites of albumin presence, substantiated by reduced immunoreactivity of endothelial and changes in vascular basement membrane markers. Taken together, degenerative events at the level of the NVU, affecting vessels, astrocytes, and neurons, seem to outweigh reconstructive processes. Considering the rapidly occurring BBB leakage and subsequent impairment of the NVU, our data support the necessity of a prompt BBB-restoring treatment as one component of rational therapeutic intervention to prevent epileptogenesis and the development of other detrimental sequelae of SE. PMID:29854942
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Newman, Andrew J; Hayes, Sarah H; Rao, Abhiram S; Allman, Brian L; Manohar, Senthilvelan; Ding, Dalian; Stolzberg, Daniel; Lobarinas, Edward; Mollendorf, Joseph C; Salvi, Richard
2015-03-15
Military personnel and civilians living in areas of armed conflict have increased risk of exposure to blast overpressures that can cause significant hearing loss and/or brain injury. The equipment used to simulate comparable blast overpressures in animal models within laboratory settings is typically very large and prohibitively expensive. To overcome the fiscal and space limitations introduced by previously reported blast wave generators, we developed a compact, low-cost blast wave generator to investigate the effects of blast exposures on the auditory system and brain. The blast wave generator was constructed largely from off the shelf components, and reliably produced blasts with peak sound pressures of up to 198dB SPL (159.3kPa) that were qualitatively similar to those produced from muzzle blasts or explosions. Exposure of adult rats to 3 blasts of 188dB peak SPL (50.4kPa) resulted in significant loss of cochlear hair cells, reduced outer hair cell function and a decrease in neurogenesis in the hippocampus. Existing blast wave generators are typically large, expensive, and are not commercially available. The blast wave generator reported here provides a low-cost method of generating blast waves in a typical laboratory setting. This compact blast wave generator provides scientists with a low cost device for investigating the biological mechanisms involved in blast wave injury to the rodent cochlea and brain that may model many of the damaging effects sustained by military personnel and civilians exposed to intense blasts. Copyright © 2015 Elsevier B.V. All rights reserved.
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Newman, Andrew J.; Hayes, Sarah H.; Rao, Abhiram S.; Allman, Brian L.; Manohar, Senthilvelan; Ding, Dalian; Stolzberg, Daniel; Lobarinas, Edward; Mollendorf, Joseph C.; Salvi, Richard
2015-01-01
Background Military personnel and civilians living in areas of armed conflict have increased risk of exposure to blast overpressures that can cause significant hearing loss and/or brain injury. The equipment used to simulate comparable blast overpressures in animal models within laboratory settings is typically very large and prohibitively expensive. New Method To overcome the fiscal and space limitations introduced by previously reported blast wave generators, we developed a compact, low-cost blast wave generator to investigate the effects of blast exposures on the auditory system and brain. Results The blast wave generator was constructed largely from off the shelf components, and reliably produced blasts with peak sound pressures of up to 198 dB SPL (159.3 kPa) that were qualitatively similar to those produced from muzzle blasts or explosions. Exposure of adult rats to 3 blasts of 188 dB peak SPL (50.4 kPa) resulted in significant loss of cochlear hair cells, reduced outer hair cell function and a decrease in neurogenesis in the hippocampus. Comparison to existing methods Existing blast wave generators are typically large, expensive, and are not commercially available. The blast wave generator reported here provides a low-cost method of generating blast waves in a typical laboratory setting. Conclusions This compact blast wave generator provides scientists with a low cost device for investigating the biological mechanisms involved in blast wave injury to the rodent cochlea and brain that may model many of the damaging effects sustained by military personnel and civilians exposed to intense blasts. PMID:25597910
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[Expression of c-jun protein after experimental rat brain concussion].
Wang, Feng; Li, Yong-hong
2010-02-01
To observe e-jun protein expression after rat brain concussion and explore the forensic pathologic markers following brain concussion. Fifty-five rats were randomly divided into brain concussion group and control group. The expression of c-jun protein was observed by immunohistochemistry. There were weak positive expression of c-jun protein in control group. In brain concussion group, however, some neutrons showed positive expression of c-jun protein at 15 min after brain concussion, and reach to the peak at 3 h after brain concussion. The research results suggest that detection of c-jun protein could be a marker to determine brain concussion and estimate injury time after brain concussion.
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Polyethylene glycol restores axonal conduction after corpus callosum transection.
Bamba, Ravinder; Riley, D Colton; Boyer, Richard B; Pollins, Alonda C; Shack, R Bruce; Thayer, Wesley P
2017-05-01
Polyethylene glycol (PEG) has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA) were used to measure mean firing rate (MFR) and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups ( P < 0.01, P < 0.05). These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion.
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Polyethylene glycol restores axonal conduction after corpus callosum transection
Bamba, Ravinder; Riley, D. Colton; Boyer, Richard B.; Pollins, Alonda C.; Shack, R. Bruce; Thayer, Wesley P.
2017-01-01
Polyethylene glycol (PEG) has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA) were used to measure mean firing rate (MFR) and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups (P < 0.01, P < 0.05). These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion. PMID:28616031
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Castel-Branco, M M; Figueiredo, I V; Falcão, A C; Macedo, T R A; Caramona, M M
2002-10-01
Given that administration vehicles and drug formulations can affect drug bioavailability, their influence on the pharmacokinetic profile of lamotrigine (LTG), a new-generation anti-epileptic drug, was studied in rats. Three different formulations administered intraperitoneally at a dose of 10 mg/kg were used: (1) LTG suspended in a 0.25% methylcelulose solution, (2) LTG dissolved in a 50% propylene glycol solution, and (3) LTG isethionate dissolved in distilled water. Plasma and brain homogenate levels were determined in order to evaluate vehicle-dependent drug absorption. The results demonstrated rapid absorption of LTG when it was administered as an aqueous solution, in contrast to a slower and more erratic absorption after the injection of either the lipophilic solution or the suspension. A plasma peak was achieved 15 min post-dose with the aqueous solution, with a brain peak being achieved 15 min later, while with the other formulations both plasma and brain homogenate peaks were reached 2 h after LTG administration. This study suggests that LTG isethionate dissolved in distilled water is the most suitable formulation for successful LTG pharmacokinetic studies in rats.
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Developmental imaging genetics: linking dopamine function to adolescent behavior.
Padmanabhan, Aarthi; Luna, Beatriz
2014-08-01
Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to non-invasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach. Copyright © 2014 Elsevier Inc. All rights reserved.
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Developmental and Regional Patterns of GAP-43 Immunoreactivity in a Metamorphosing Brain
Simmons, Andrea Megela; Tanyu, Leslie H.; Horowitz, Seth S.; Chapman, Judith A.; Brown, Rebecca A.
2012-01-01
Growth-associated protein-43 is typically expressed at high levels in the nervous system during development. In adult animals, its expression is lower, but still observable in brain areas showing structural or functional plasticity. We examined patterns of GAP-43 immunoreactivity in the brain of the bullfrog, an animal whose nervous system undergoes considerable reorganization across metamorphic development and retains a strong capacity for plasticity in adulthood. Immunolabeling was mostly diffuse in hatchling tadpoles, but became progressively more discrete as larval development proceeded. In many brain areas, intensity of immunolabel peaked at metamorphic climax, the time of final transition from aquatic to semi-terrestrial life. Changes in intensity of GAP-43 expression in the medial vestibular nucleus, superior olivary nucleus, and torus semicircularis appeared correlated with stage-dependent functional changes in processing auditory stimuli. Immunolabeling in the Purkinje cell layer of the cerebellum and in the cerebellar nucleus was detectable at most developmental time points. Heavy immunolabel was present from early larval stages through the end of climax in the thalamus (ventromedial, anterior, posterior, central nuclei). Immunolabel in the tadpole telencephalon was observed around the lateral ventricles, and in the medial septum and ventral striatum. In postmetamorphic animals, immunoreactivity was confined mainly to the ventricular zones and immediately adjacent cell layers. GAP-43 expression was present in olfactory, auditory and optic cranial nerves throughout larval and postmetamorphic life. The continued expression of GAP-43 in brain nuclei and in cranial nerves throughout development and into adulthood reflects the high regenerative potential of the bullfrog’s central nervous system. PMID:18431052
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Xu, Pan; Du, Shou-Ying; Lu, Yang; Bai, Jie; Liu, Hui-Min; Du, Qiu; Chen, Zhen-Zhen; Wang, Zhen
2014-06-01
To establish a UPLC-MS/MS method for the simultaneous determination of geniposide, genipin 1-O-beta-D-gentiobioside and geniposidic acid in rat brains and study the brain pharmacokinetics of the three iridoid glycosides in stroke rat after the oral administration of Xingnaojing. In this experiment, brain samples were precipitated with protein for twice. Acquity BEH C18 column was adopted, with acetonitrile-0.1% formic acid-water as the mobile phase for gradient elution. ESI source was adopted for mass spectra; multiple reaction monitoring (MRM) was conducted to detect negative ions. The time for sample analysis was 3.5 min. the results showed good linear relations among the three iridoid glycosides, with the extraction recovery between 99.6% and 114.3%, good intra- and inter-day precisions and accuracies and stability in line with the requirements. The t1/2 and MRT in the three components were similar in brains of stroke rats. Geniposide and genipin 1-O-beta-D-gentiobioside showed double peaks; where as geniposidic acid showed a single peak. In conclusion, the method is so specific, sensitive, accurate and reliable that it can be used to study the brain pharmacokinetics of Xingnaojing oral preparation.
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Gangliosides and Ceramides Change in a Mouse Model of Blast Induced Traumatic Brain Injury
2013-01-01
Explosive detonations generate atmospheric pressure changes that produce nonpenetrating blast induced “mild” traumatic brain injury (bTBI). The structural basis for mild bTBI has been extremely controversial. The present study applies matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging to track the distribution of gangliosides in mouse brain tissue that were exposed to very low level of explosive detonations (2.5–5.5 psi peak overpressure). We observed major increases of the ganglioside GM2 in the hippocampus, thalamus, and hypothalamus after a single blast exposure. Moreover, these changes were accompanied by depletion of ceramides. No neurological or brain structural signs of injury could be inferred using standard light microscopic techniques. The first source of variability is generated by the Latency between blast and tissue sampling (peak intensity of the blast wave). These findings suggest that subtle molecular changes in intracellular membranes and plasmalemma compartments may be biomarkers for biological responses to mild bTBI. This is also the first report of a GM2 increase in the brains of mature mice from a nongenetic etiology. PMID:23590251
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Hydrogen Ion Buffering During Complete Brain Ischemia
KRAIG, RICHARD P.; PULSINELLI, WILLIAM A.; PLUM, FRED
2011-01-01
As a first step to quantify [H+] changes in brain during ischemia we used H+-selective microelectrodes and enzyme fluorometric techniques to describe the relationship between interstitial [H+] ([H+]o) and peak tissue lactate after cardiac arrest. We found a step function relationship between [H+]o and tissue lactate rather than the linear titration expected in a homogeneous protein solution. Within a blood glucose range from 3–7 mM, brain lactate rose from 8–13 mmol/kg along with a rise in [H+]o of 99 ± 6 nM (0.44 ± 0.02 pH). At higher blood glucose levels (17–80 mM), brain lactate accumulated to levels of 16–31 mmol/kg; concurrently [H+]o rose by 608 ± 16 nM (1.07 ± 0.02 pH). The unchanging level of [H+]o between 8–13 and 16–31 mmol/kg lactate implies that [H+]o is at a steady-state, but not equilibrium with respect to [H+] in other brain compartments. We propose that ion-transport characteristics of astroglia account for the observed relationship of [H+]o to tissue lactate during complete ischemia and suggest that brain infarction develops after plasma membranes in brain cells can no longer transport ions to regulate [H+]. PMID:4041829
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Brenhouse, Heather C.; Andersen, Susan L.
2011-01-01
Adolescence is a transitional period between childhood and adulthood that encompasses vast changes within brain systems that parallel some, but not all, behavioral changes. Elevations in emotional reactivity and reward processing follow an inverted U shape in terms of onset and remission, with the peak occurring during adolescence. However, cognitive processing follows a more linear course of development. This review will focus on changes within key structures and will highlight the relationships between brain changes and behavior, with evidence spanning from functional magnetic resonance imaging (fMRI) in humans to molecular studies of receptor and signaling factors in animals. Adolescent changes in neuronal substrates will be used to understand how typical and atypical behaviors arise during adolescence. We draw upon clinical and preclinical studies to provide a neural framework for defining adolescence and its role in the transition to adulthood. PMID:21600919
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Tagge, Chad A; Fisher, Andrew M; Minaeva, Olga V; Gaudreau-Balderrama, Amanda; Moncaster, Juliet A; Zhang, Xiao-Lei; Wojnarowicz, Mark W; Casey, Noel; Lu, Haiyan; Kokiko-Cochran, Olga N; Saman, Sudad; Ericsson, Maria; Onos, Kristen D; Veksler, Ronel; Senatorov, Vladimir V; Kondo, Asami; Zhou, Xiao Z; Miry, Omid; Vose, Linnea R; Gopaul, Katisha R; Upreti, Chirag; Nowinski, Christopher J; Cantu, Robert C; Alvarez, Victor E; Hildebrandt, Audrey M; Franz, Erich S; Konrad, Janusz; Hamilton, James A; Hua, Ning; Tripodis, Yorghos; Anderson, Andrew T; Howell, Gareth R; Kaufer, Daniela; Hall, Garth F; Lu, Kun P; Ransohoff, Richard M; Cleveland, Robin O; Kowall, Neil W; Stein, Thor D; Lamb, Bruce T; Huber, Bertrand R; Moss, William C; Friedman, Alon; Stanton, Patric K; McKee, Ann C; Goldstein, Lee E
2018-01-01
Abstract The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood–brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood–brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath. PMID:29360998
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Zhao, Wei; Ji, Songbai
2017-04-01
Head angular velocity, instead of acceleration, is more predictive of brain strains. Surprisingly, no study exists that investigates how shape variation in angular velocity profiles affects brain strains, beyond characteristics such as peak magnitude and impulse duration. In this study, we evaluated brain strain uncertainty due to variation in angular velocity profiles and further compared with that resulting from simplifying the profiles into idealized shapes. To do so, we used reconstructed head impacts from American National Football League for shape extraction and simulated head uniaxial coronal rotations from onset to full stop. The velocity profiles were scaled to maintain an identical peak velocity magnitude and duration in order to isolate the shape for investigation. Element-wise peak maximum principal strains from 44 selected impacts were obtained. We found that the shape of angular velocity profile could significantly affect brain strain magnitude (e.g., percentage difference of 4.29-17.89 % in the whole brain relative to the group average, with cumulative strain damage measure (CSDM) uncertainty range of 23.9 %) but not pattern (correlation coefficient of 0.94-0.99). Strain differences resulting from simplifying angular velocity profiles into idealized shapes were largely within the range due to shape variation, in both percentage difference and CSDM (signed difference of 3.91 % on average, with a typical range of 0-6 %). These findings provide important insight into the uncertainty or confidence in the performance of kinematics-based injury metrics. More importantly, they suggest the feasibility to simplify head angular velocity profiles into idealized shapes, at least within the confinements of the profiles evaluated, to enable real-time strain estimation via pre-computation in the future.
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Zhao, Wei; Ji, Songbai
2016-01-01
Head angular velocity, instead of acceleration, is more predictive of brain strains. Surprisingly, no study exists that investigates how shape variation in angular velocity profiles affects brain strains, beyond characteristics such as peak magnitude and impulse duration. In this study, we evaluated brain strain uncertainty due to variation in angular velocity profiles, and further compared with that resulting from simplifying the profiles into idealized shapes. To do so, we used reconstructed head impacts from American National Football League for shape extraction, and simulated head uniaxial coronal rotations from onset to full stop. The velocity profiles were scaled to maintain an identical peak velocity magnitude and duration in order to isolate the shape for investigation. Element-wise peak maximum principal strains from 44 selected impacts were obtained. We found that the shape of angular velocity profile could significantly affect brain strain magnitude (e.g., percentage difference of 4.29–17.89% in the whole-brain relative to the group average, with cumulative strain damage measure (CSDM) uncertainty range of 23.9%) but not pattern (correlation coefficient of 0.94–0.99). Strain differences resulting from simplifying angular velocity profiles into idealized shapes were largely within the range due to shape variation, in both percentage difference and CSDM (signed difference of 3.91% on average, with a typical range of 0–6%). These findings provide important insight into the uncertainty or confidence in the performance of kinematics-based injury metrics. More importantly, they suggest the feasibility to simplify head angular velocity profiles into idealized shapes, at least within the confinements of the profiles evaluated, to enable real-time strain estimation via pre-computation in the future. PMID:27644441
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NASA Astrophysics Data System (ADS)
Whelan, Harry T.; Houle, John M.; Bajic, Dawn M.; Schmidt, Meic H.; Reichert, Kenneth W.; Meyer, Glenn A.
1998-01-01
Photodynamic therapy (PDT) is a cancer treatment modality that recently has been applied as adjuvant therapy for brain tumors. PDT consists of intravenously injecting a photosensitizer, which preferentially accumulates in tumor cells, into a patient and then activating the photosensitizer with a light source. This results in free radical generation followed by cell death. The development of more effective light sources for PDT of brain tumors has been facilitated by applications of space light-emitting diode array technology; thus permitting deeper tumor penetration of light and use of better photosensitizers. Currently, the most commonly used photosensitizer for brain tumor PDT is Photofrin®. Photofrin® is a heterogeneous mixture of compounds derived from hematoporphyrin. Photofrin® is activated with a 630 nm laser light and does destroy tumor cells in animal models and humans. However, treatment failure does occur using this method. Most investigators attribute this failure to the limited penetration of brain tissue by a 630 nm laser light and to the fact that Photofrin® has only a minor absorption peak at 630 nm, meaning that only a small fraction of the chemical is activated. Benzoporphyrin Derivative Monoacid Ring A (BPD) is a new, second generation photosensitizer that can potentially improve PDT for brain tumors. BPD has a major absorption peak at 690 nm, which gives it two distinct advantages over Photofrin®. First, longer wavelengths of light penetrate brain tissue more easily so that larger tumors could be treated, and second, the major absorption peak means that a larger fraction of the drug is activated upon exposure to light. In the first part of this project we have studied the tumoricidal effects of BPD in vitro using 2A9 canine glioma and U373 human glioblastoma cell cultures. Using light emitting diodes (LED) with a peak emission of 688 nm as a light source, cell kill of up to 86 percent was measured in these cell lines by tumor DNA synthesis reduction. The effectiveness of BPD against tumor cells in vitro thus established, we have taken the first step toward determining its effectiveness in vivo. The second part of this project consisted of experiments performed to determine the maximum tolerated dose (MTD) of both BPD and LED light. At a light dose of 100 J/cm2, skin damage and neurotoxicity were seen at a BPD dose of 1.0 mg/kg, but not at a dose of 0.75 mg/kg. When BPD remained constant at 0.75 mg/kg, skin damage was seen at light dosages of 125 J/cm2, 150 J/cm2 and 175 J/cm2. One dog also died at a light dose of 175 J/cm2. Further studies will be needed to determine the effectiveness of BPD against tumor cells in vivo.
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Flodin, Pär; Jonasson, Lars S.; Riklund, Katrin; Nyberg, Lars; Boraxbekk, C. J.
2017-01-01
Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64–78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO2-peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO2-peak was negativly related to BOLD-signal fluctuations (BOLDSTD) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO2-related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross-sectional or longitudinal relationships between VO2-peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas. PMID:28848424
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Flodin, Pär; Jonasson, Lars S; Riklund, Katrin; Nyberg, Lars; Boraxbekk, C J
2017-01-01
Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64-78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO 2 -peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO 2 -peak was negativly related to BOLD-signal fluctuations (BOLD STD ) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO 2 -related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross-sectional or longitudinal relationships between VO 2 -peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas.
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EEG during pedaling: Evidence for cortical control of locomotor tasks
Jain, Sanket; Gourab, Krishnaj; Schindler-Ivens, Sheila; Schmit, Brian D.
2014-01-01
Objective This study characterized the brain electrical activity during pedaling, a locomotor-like task, in humans. We postulated that phasic brain activity would be associated with active pedaling, consistent with a cortical role in locomotor tasks. Methods Sixty four channels of electroencephalogram (EEG) and 10 channels of electromyogram (EMG) data were recorded from 10 neurologically-intact volunteers while they performed active and passive (no effort) pedaling on a custom-designed stationary bicycle. Ensemble averaged waveforms, 2 dimensional topographic maps and amplitude of the β (13–35 Hz) frequency band were analyzed and compared between active and passive trials. Results The peak-to-peak amplitude (peak positive–peak negative) of the EEG waveform recorded at the Cz electrode was higher in the passive than the active trials (p < 0.01). β-band oscillations in electrodes overlying the leg representation area of the cortex were significantly desynchronized during active compared to the passive pedaling (p < 0.01). A significant negative correlation was observed between the average EEG waveform for active trials and the composite EMG (summated EMG from both limbs for each muscle) of the rectus femoris (r = −0.77, p < 0.01) the medial hamstrings (r = −0.85, p < 0.01) and the tibialis anterior (r = −0.70, p < 0.01) muscles. Conclusions These results demonstrated that substantial sensorimotor processing occurs in the brain during pedaling in humans. Further, cortical activity seemed to be greatest during recruitment of the muscles critical for transitioning the legs from flexion to extension and vice versa. Significance This is the first study demonstrating the feasibility of EEG recording during pedaling, and owing to similarities between pedaling and bipedal walking, may provide valuable insight into brain activity during locomotion in humans. PMID:23036179
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Watanabe, H; Takaya, N; Mitsumori, F
2008-06-01
Localized two-dimensional constant-time correlation spectroscopy (CT-COSY) was used to resolve glutamate (Glu), gamma-aminobutyric acid (GABA), and glutamine (Gln) in the human brain at 4.7 T. In this method, three-dimensional localization was achieved using three radio frequency pulses of the CT-COSY module for slice selection. As this sequence could decouple JHH along the F1 direction, peak resolution of metabolites was improved even on a magnitude-mode display. In experiments on a phantom containing N-acetylaspartate, creatine, Glu, Gln, and GABA with a constant time delay (Tct) of 110 ms, cross peaks of Glu, Gln, and GABA were obtained on a spectrum processed with standard sine-bell windows, which emphasize sine-dependent signals along the t2 direction. In contrast, diagonal peaks of Glu C4H at 2.35 ppm, GABA C2H at 2.28 ppm, and Gln C4H at 2.44 ppm were resolved on a spectrum processed with Gaussian windows, which emphasize cosine-dependent signals along t2. Human brain spectra were obtained from a 27 mL voxel within the parieto-occipital region using a volume transverse electromagnetic (TEM) coil for both transmission and reception. Tct was 110 ms; the total scan time was 30 min. Diagonal peaks of Glu C4H, GABA C2H, and Gln C4H were also resolved on the spectrum processed with Gaussian windows. These results show that the localized two-dimensional CT-COSY method featuring 1H decoupling along the F1 direction could resolve Glu, GABA, and Gln signals in the human brain. Copyright (c) 2008 John Wiley & Sons, Ltd.
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Hayes, Scott M.; Hayes, Jasmeet P.; Williams, Victoria J.; Liu, Huiting; Verfaellie, Mieke
2017-01-01
Older adults (OA), relative to young adults (YA), exhibit age-related alterations in functional Magnetic Resonance Imaging (fMRI) activity during associative encoding, which contributes to deficits in source memory. Yet, there are remarkable individual differences in brain health and memory performance among OA. Cardiorespiratory fitness (CRF) is one individual difference factor that may attenuate brain aging, and thereby contribute to enhanced source memory in OA. To examine this possibility, 26 OA and 31 YA completed a treadmill-based exercise test to evaluate CRF (peak VO2) and fMRI to examine brain activation during a face-name associative encoding task. Our results indicated that in OA, peak VO2 was positively associated with fMRI activity during associative encoding in multiple regions including bilateral prefrontal cortex, medial frontal cortex, bilateral thalamus and left hippocampus. Next, a conjunction analysis was conducted to assess whether CRF influenced age-related differences in fMRI activation. We classified OA as high or low CRF and compared their activation to YA. High fit OA (HFOA) showed fMRI activation more similar to YA than low fit OA (LFOA) (i.e., reduced age-related differences) in multiple regions including thalamus, posterior and prefrontal cortex. Conversely, in other regions, primarily in prefrontal cortex, HFOA, but not LFOA, demonstrated greater activation than YA (i.e., increased age-related differences). Further, fMRI activity in these brain regions was positively associated with source memory among OA, with a mediation model demonstrating that associative encoding activation in medial frontal cortex indirectly influenced the relationship between peak VO2 and subsequent source memory performance. These results indicate that CRF may contribute to neuroplasticity among OA, reducing age-related differences in some brain regions, consistent with the brain maintenance hypothesis, but accentuating age-differences in other regions, consistent with the brain compensation hypothesis. PMID:28161031
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Hayes, Scott M; Hayes, Jasmeet P; Williams, Victoria J; Liu, Huiting; Verfaellie, Mieke
2017-06-01
Older adults (OA), relative to young adults (YA), exhibit age-related alterations in functional Magnetic Resonance Imaging (fMRI) activity during associative encoding, which contributes to deficits in source memory. Yet, there are remarkable individual differences in brain health and memory performance among OA. Cardiorespiratory fitness (CRF) is one individual difference factor that may attenuate brain aging, and thereby contribute to enhanced source memory in OA. To examine this possibility, 26 OA and 31 YA completed a treadmill-based exercise test to evaluate CRF (peak VO 2 ) and fMRI to examine brain activation during a face-name associative encoding task. Our results indicated that in OA, peak VO 2 was positively associated with fMRI activity during associative encoding in multiple regions including bilateral prefrontal cortex, medial frontal cortex, bilateral thalamus and left hippocampus. Next, a conjunction analysis was conducted to assess whether CRF influenced age-related differences in fMRI activation. We classified OA as high or low CRF and compared their activation to YA. High fit OA (HFOA) showed fMRI activation more similar to YA than low fit OA (LFOA) (i.e., reduced age-related differences) in multiple regions including thalamus, posterior and prefrontal cortex. Conversely, in other regions, primarily in prefrontal cortex, HFOA, but not LFOA, demonstrated greater activation than YA (i.e., increased age-related differences). Further, fMRI activity in these brain regions was positively associated with source memory among OA, with a mediation model demonstrating that associative encoding activation in medial frontal cortex indirectly influenced the relationship between peak VO 2 and subsequent source memory performance. These results indicate that CRF may contribute to neuroplasticity among OA, reducing age-related differences in some brain regions, consistent with the brain maintenance hypothesis, but accentuating age-differences in other regions, consistent with the brain compensation hypothesis. Published by Elsevier Ltd.
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Beyond stereotypes of adolescent risk taking: Placing the adolescent brain in developmental context.
Romer, Daniel; Reyna, Valerie F; Satterthwaite, Theodore D
2017-10-01
Recent neuroscience models of adolescent brain development attribute the morbidity and mortality of this period to structural and functional imbalances between more fully developed limbic regions that subserve reward and emotion as opposed to those that enable cognitive control. We challenge this interpretation of adolescent development by distinguishing risk-taking that peaks during adolescence (sensation seeking and impulsive action) from risk taking that declines monotonically from childhood to adulthood (impulsive choice and other decisions under known risk). Sensation seeking is primarily motivated by exploration of the environment under ambiguous risk contexts, while impulsive action, which is likely to be maladaptive, is more characteristic of a subset of youth with weak control over limbic motivation. Risk taking that declines monotonically from childhood to adulthood occurs primarily under conditions of known risks and reflects increases in executive function as well as aversion to risk based on increases in gist-based reasoning. We propose an alternative Life-span Wisdom Model that highlights the importance of experience gained through exploration during adolescence. We propose, therefore, that brain models that recognize the adaptive roles that cognition and experience play during adolescence provide a more complete and helpful picture of this period of development. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Inhomogeneity in optical properties of rat brain: a study for LLLT dosimetry
NASA Astrophysics Data System (ADS)
Sousa, Marcelo V. P.; Prates, Renato; Kato, Ilka T.; Sabino, Caetano P.; Yoshimura, Tania M.; Suzuki, Luis C.; Magalhães, Ana C.; Yoshimura, Elisabeth M.; Ribeiro, Martha S.
2013-03-01
Over the last few years, low-level light therapy (LLLT) has shown an incredible suitability for a wide range of applications for central nervous system (CNS) related diseases. In this therapeutic modality light dosimetry is extremely critical so the study of light propagation through the CNS organs is of great importance. To better understand how light intensity is delivered to the most relevant neural sites we evaluated optical transmission through slices of rat brain point by point. We experimented red (λ = 660 nm) and near infrared (λ = 808 nm) diode laser light analyzing the light penetration and distribution in the whole brain. A fresh Wistar rat (Rattus novergicus) brain was cut in sagittal slices and illuminated with a broad light beam. A high-resolution digital camera was employed to acquire data of transmitted light. Spatial profiles of the light transmitted through the sample were obtained from the images. Peaks and valleys in the profiles show sites where light was less or more attenuated. The peak intensities provide information about total attenuation and the peak widths are correlated to the scattering coefficient at that individual portion of the sample. The outcomes of this study provide remarkable information for LLLT dose-dependent studies involving CNS and highlight the importance of LLLT dosimetry in CNS organs for large range of applications in animal and human diseases.
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Mansor, Syahir; Pfaehler, Elisabeth; Heijtel, Dennis; Lodge, Martin A; Boellaard, Ronald; Yaqub, Maqsood
2017-12-01
In longitudinal oncological and brain PET/CT studies, it is important to understand the repeatability of quantitative PET metrics in order to assess change in tracer uptake. The present studies were performed in order to assess precision as function of PET/CT system, reconstruction protocol, analysis method, scan duration (or image noise), and repositioning in the field of view. Multiple (repeated) scans have been performed using a NEMA image quality (IQ) phantom and a 3D Hoffman brain phantom filled with 18 F solutions on two systems. Studies were performed with and without randomly (< 2 cm) repositioning the phantom and all scans (12 replicates for IQ phantom and 10 replicates for Hoffman brain phantom) were performed at equal count statistics. For the NEMA IQ phantom, we studied the recovery coefficients (RC) of the maximum (SUV max ), peak (SUV peak ), and mean (SUV mean ) uptake in each sphere as a function of experimental conditions (noise level, reconstruction settings, and phantom repositioning). For the 3D Hoffman phantom, the mean activity concentration was determined within several volumes of interest and activity recovery and its precision was studied as function of experimental conditions. The impact of phantom repositioning on RC precision was mainly seen on the Philips Ingenuity PET/CT, especially in the case of smaller spheres (< 17 mm diameter, P < 0.05). This effect was much smaller for the Siemens Biograph system. When exploring SUV max , SUV peak , or SUV mean of the spheres in the NEMA IQ phantom, it was observed that precision depended on phantom repositioning, reconstruction algorithm, and scan duration, with SUV max being most and SUV peak least sensitive to phantom repositioning. For the brain phantom, regional averaged SUVs were only minimally affected by phantom repositioning (< 2 cm). The precision of quantitative PET metrics depends on the combination of reconstruction protocol, data analysis methods and scan duration (scan statistics). Moreover, precision was also affected by phantom repositioning but its impact depended on the data analysis method in combination with the reconstructed voxel size (tissue fraction effect). This study suggests that for oncological PET studies the use of SUV peak may be preferred over SUV max because SUV peak is less sensitive to patient repositioning/tumor sampling. © 2017 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.
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Brain MRI and MR Spectroscopy Findings in Children with Nutritional Vitamin B12 Deficiency.
Ekici, F; Tekbas, G; Hattapoğlu, S; Yaramış, A; Önder, H; Bilici, A
2016-06-01
Our aim in this study was to analyze the findings of brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of children with vitamin B12 deficiency. This study included 14 cases. The findings of brain MRI and MRS in all cases were investigated. Four patients had been followed up and mean follow-up time 71.8 (59-85) day. Eight patients of the cases (57 %) had at least one abnormal MRI finding. The most commonly found MRI findings were thinning of the corpus callosum and brain atrophy, respectively. The mean ratio of NAA/Cr and Cho/Cr were measured in MRS, with values of 1.31 ± 0.17 and 1.04 ± 0.27, respectively. In two of three patients with abnormal MRI studies at presentation, subsequent MRI showed improvement while one patient remained unchanged. An increase in the ratios of metabolites were found in one case with control MRS. There was no lactate peak. Brain MRI was abnormal in more than half of the cases of children with vitamin B12 deficiency. Our radiologic findings similar with literature. There was no identifiable lactate peak. B12 deficiency could be the cause of the thinning of the corpus callosum and brain atrophy in the children that were given a brain MRI.
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Portnow, Jana; Badie, Behnam; Chen, Mike; Liu, An; Blanchard, Suzette; Synold, Timothy W
2009-11-15
Intracerebral microdialysis (ICMD) is an accepted method for monitoring changes in neurochemistry from acute brain injury. The goal of this pilot study was to determine the feasibility of using ICMD to examine the neuropharmacokinetics of temozolomide in brain interstitium following oral administration. Patients with primary or metastatic brain tumors had a microdialysis catheter placed in peritumoral brain tissue at the time of surgical debulking. Computerized tomography scan confirmed the catheter location. Patients received a single oral dose of temozolomide (150 mg/m2) on the first postoperative day, serial plasma and ICMD samples were collected over 24 hours, and temozolomide concentrations were determined by tandem mass spectrometry. Nine patients were enrolled. Dialysate and plasma samples were successfully collected from seven of the nine patients. The mean temozolomide areas under the concentration-time curve (AUC) in plasma and brain interstitium were 17.1 and 2.7 microg/mL x hour, with an average brain interstitium/plasma AUC ratio of 17.8%. The mean peak temozolomide concentration in the brain was 0.6 +/- 0.3 microg/mL, and the mean time to reach peak level in brain was 2.0 +/- 0.8 hours. The use of ICMD to measure the neuropharmacokinetics of systemically administered chemotherapy is safe and feasible. Concentrations of temozolomide in brain interstitium obtained by ICMD are consistent with published data obtained in a preclinical ICMD model, as well as from clinical studies of cerebrospinal fluid. However, the delayed time required to achieve maximum temozolomide concentrations in brain suggests that current chemoradiation regimens may be improved by administering temozolomide 2 to 3 hours before radiation.
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Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease
Sakic, Boris; Kirkham, David L.; Ballok, David A.; Mwanjewe, James; Fearon, Ian M.; Macri, Joseph; Yu, Guanhua; Sidor, Michelle M.; Denburg, Judah A.; Szechtman, Henry; Lau, Jonathan; Ball, Alexander K.; Doering, Laurie C.
2006-01-01
Brain atrophy, neurologic and psychiatric (NP) manifestations are common complications in the systemic autoimmune disease, lupus erythematosus (SLE). Here we show that the cerebrospinal fluid (CSF) from autoimmune MRL-lpr mice and a deceased NP-SLE patient reduce the viability of brain cells which proliferate in vitro. This detrimental effect was accompanied by periventricular neurodegeneration in the brains of autoimmune mice and profound in vivo neurotoxicity when their CSF was administered to the CNS of a rat. Multiple ionic responses with microfluorometry and protein peaks on electropherograms suggest more than one mechanism of cellular demise. Similar to the CSF from diseased MRL-lpr mice, the CSF from a deceased SLE patient with a history of psychosis, memory impairment, and seizures, reduced viability of the C17.2 neural stem cell line. Proposed mechanisms of cytotoxicity involve binding of intrathecally synthesized IgG autoantibodies to target(s) common to different mammalian species and neuronal populations. More importantly, these results indicate that the viability of proliferative neural cells can be compromised in systemic autoimmune disease. Antibody-mediated lesions of germinal layers may impair the regenerative capacity of the brain in NP-SLE and possibly, brain development and function in some forms of CNS disorders in which autoimmune phenomena have been documented. PMID:16198428
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Morrow, Bret A.; Roth, Robert H.; Redmond, D. Eugene; Sladek, John R.; Elsworth, John D.
2012-01-01
Natural cell death (NCD) by apoptosis is a normal developmental event in most neuronal populations, and is a determinant of the eventual size of a population. We decided to examine the timing and extent of NCD of the midbrain dopamine system in a primate species, as dopamine deficiency or excess has been implicated in several disorders. Genetic or environmental differences may alter the extent of NCD and predispose individuals to neurological or psychiatric diseases. In developing rats, NCD in the midbrain dopamine system has been observed to start at the end of gestation and peak in the postnatal period. In fetal monkey brains, apoptosis in midbrain DA neurons was identified histologically by chromatin clumping in tyrosine hydroxylase-positive cells, and confirmed by TUNEL and active caspase-3 staining. A distinct peak of NCD occurred at about E80, midway through gestation in this species. We estimate that at least 50% of the population may be lost in this process. In other brains we determined biochemically that the onset of apoptosis coincides with the time of greatest rate of increase of striatal DA concentration. Thus, marked apoptotic NCD occurs in the primate midbrain dopamine system half-way through gestation, and appears to be associated with the rapid developmental increase in striatal dopamine innervation. PMID:17313945
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Pasquesi, Stephanie A; Margulies, Susan S
2018-01-01
Computational models are valuable tools for studying tissue-level mechanisms of traumatic brain injury, but to produce more accurate estimates of tissue deformation, these models must be validated against experimental data. In this study, we present in situ measurements of brain-skull displacement in the neonatal piglet head ( n = 3) at the sagittal midline during six rapid non-impact rotations (two rotations per specimen) with peak angular velocities averaging 51.7 ± 1.4 rad/s. Marks on the sagittally cut brain and skull/rigid potting surfaces were tracked, and peak values of relative brain-skull displacement were extracted and found to be significantly less than values extracted from a previous axial plane model. In a finite element model of the sagittally transected neonatal porcine head, the brain-skull boundary condition was matched to the measured physical experiment data. Despite smaller sagittal plane displacements at the brain-skull boundary, the corresponding finite element boundary condition optimized for sagittal plane rotations is far less stiff than its axial counterpart, likely due to the prominent role of the boundary geometry in restricting interface movement. Finally, bridging veins were included in the finite element model. Varying the bridging vein mechanical behavior over a previously reported range had no influence on the brain-skull boundary displacements. This direction-specific sagittal plane boundary condition can be employed in finite element models of rapid sagittal head rotations.
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NASA Astrophysics Data System (ADS)
Sarvghad-Moghaddam, H.; Rezaei, A.; Ziejewski, M.; Karami, G.
2017-11-01
Upon impingement of blast waves on the head, stress waves generated at the interface of the skull are transferred into the cranium and the brain tissue and may cause mild to severe blast traumatic brain injury. The intensity of the shock front, defined by the blast overpressure (BoP), that is, the blast-induced peak static overpressure, significantly affects head kinematics as well as the tissue responses of the brain. While evaluation of global linear and rotational accelerations may be feasible, an experimental determination of dynamic responses of the brain in terms of intracranial pressure (ICP), maximum shear stress (MSS), and maximum principal strain (MPS) is almost impossible. The main objective of this study is to investigate possible correlations between head accelerations and the brain's ICP, MSS, and MPS. To this end, three different blasts were simulated by modeling the detonation of 70, 200, and 500 g of TNT at a fixed distance from the head, corresponding to peak BoPs of 0.52, 1.2, and 2 MPa, respectively. A nonlinear multi-material finite element algorithm was implemented in the LS-DYNA explicit solver. Fluid-solid interaction between the blast waves and head was modeled using a penalty-based method. Strong correlations were found between the brain's dynamic responses and both global linear and rotational accelerations at different blast intensities (R^{2 }≥98%), implying that global kinematic parameters of the head might be strong predictors of brain tissue biomechanical parameters.
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Fetal methylmercury poisoning: new data on clinical and toxicological aspects
DOE Office of Scientific and Technical Information (OSTI.GOV)
Marsh, D.O.; Myers, G.J.; Clarkson, T.W.
1977-01-01
Fetal methylmercury (MeHg) poisoning causing severe brain damage has been reported previously but dose-response data for critical levels of MeHg have been inadequate. Following the consumption of MeHg contaminated bread in Iraq, hair samples were obtained from women who had been pregnant during MeHg exposure and consecutive segments of hair were analyzed to provide peak hair mercury concentrations. When last examined the children were aged 4/sup 1///sub 2/ to 5 years. Only 4 of the 29 children had severe neurological signs but mild spastic diplegia was observed. Ten mothers had peak hair mercury concentrations between 112 and 384 parts permore » million (ppM). Their children had the following abnormalities (percentages in parentheses refer to findings in the children of 15 mothers with peak hair mercury levels less than 25 ppM); early motor retardation 50%; delayed speech 70% (7%); mental retardation 40%; convulsive disorder 30%; extensor plantar 55%; neurological signs other than plantars 40%; small head 40%; short stature 70%. MeHg induced fetal brain damage with maternal hair mercury concentrations as low as 112 to 384 ppM has not been reported previously and indicates the particular susceptibility of the fetal brain.« less
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Tagge, Chad A; Fisher, Andrew M; Minaeva, Olga V; Gaudreau-Balderrama, Amanda; Moncaster, Juliet A; Zhang, Xiao-Lei; Wojnarowicz, Mark W; Casey, Noel; Lu, Haiyan; Kokiko-Cochran, Olga N; Saman, Sudad; Ericsson, Maria; Onos, Kristen D; Veksler, Ronel; Senatorov, Vladimir V; Kondo, Asami; Zhou, Xiao Z; Miry, Omid; Vose, Linnea R; Gopaul, Katisha R; Upreti, Chirag; Nowinski, Christopher J; Cantu, Robert C; Alvarez, Victor E; Hildebrandt, Audrey M; Franz, Erich S; Konrad, Janusz; Hamilton, James A; Hua, Ning; Tripodis, Yorghos; Anderson, Andrew T; Howell, Gareth R; Kaufer, Daniela; Hall, Garth F; Lu, Kun P; Ransohoff, Richard M; Cleveland, Robin O; Kowall, Neil W; Stein, Thor D; Lamb, Bruce T; Huber, Bertrand R; Moss, William C; Friedman, Alon; Stanton, Patric K; McKee, Ann C; Goldstein, Lee E
2018-02-01
The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood-brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood-brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath.awx350media15713427811001. © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain.
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Solubilization and purification of melatonin receptors from lizard brain
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rivkees, S.A.; Conron, R.W. Jr.; Reppert, S.M.
Melatonin receptors in lizard brain were identified and characterized using {sup 125}I-labeled melatonin (({sup 125}I)MEL) after solubilization with the detergent digitonin. Saturation studies of solubilized material revealed a high affinity binding site, with an apparent equilibrium dissociation constant of 181 +/- 45 pM. Binding was reversible and inhibited by melatonin and closely related analogs, but not by serotonin or norepinephrine. Treatment of solubilized material with the non-hydrolyzable GTP analog, guanosine 5'-(3-O-thiotriphosphate) (GTP-gamma-S), significantly reduced receptor affinity. Gel filtration chromatography of solubilized melatonin receptors revealed a high affinity, large (Mr 400,000) peak of specific binding. Pretreatment with GTP-gamma-S before solubilization resultedmore » in elution of a lower affinity, smaller (Mr 150,000) peak of specific binding. To purify solubilized receptors, a novel affinity chromatography resin was developed by coupling 6-hydroxymelatonin with Epoxy-activated Sepharose 6B. Using this resin, melatonin receptors were purified approximately 10,000-fold. Purified material retained the pharmacologic specificity of melatonin receptors. These results show that melatonin receptors that bind ligand after detergent treatment can be solubilized and substantially purified by affinity chromatography.« less
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Temperature monitoring during cardiopulmonary bypass--do we undercool or overheat the brain?
Kaukuntla, Hemanth; Harrington, Deborah; Bilkoo, Inderaj; Clutton-Brock, Tom; Jones, Timothy; Bonser, Robert S
2004-09-01
Brain cooling is an essential component of aortic surgery requiring circulatory arrest and inadequate cooling may lead to brain injury. Similarly, brain hyperthermia during the rewarming phase of cardiopulmonary bypass may also lead to neurological injury. Conventional temperature monitoring sites may not reflect the core brain temperature (Tdegrees). We compared jugular bulb venous temperatures (JB) during deep hypothermic circulatory arrest and normothermic bypass with Nasopharyngeal (NP), Arterial inflow (AI), Oesophageal (O), Venous return (VR), Bladder (B) and Orbital skin (OS) temperatures. 18 patients undergoing deep hypothermia (DH) and 8 patients undergoing normothermic bypass (mean bladder Tdegrees-36.29 degreesC) were studied. For DH, cooling was continued to 15 degreesC NP (mean cooling time-66 min). At pre-determined arterial inflow Tdegrees, NP, JB and O Tdegree's were measured. A 6-channel recorder continuously recorded all Tdegree's using calibrated thermocouples. During the cooling phase of DH, NP lagged behind AI and JB Tdegree's. All these equilibrated at 15 degreesC. During rewarming, JB and NP lagged behind AI and JB was higher than NP at any time point. During normothermic bypass, although NP was reflective of the AI and JB Tdegrees trends, it underestimated peak JB Tdegrees (P=0.001). Towards the end of bypass, peak JB was greater than the arterial inflow Tdegrees (P=0.023). If brain venous outflow Tdegrees (JB) accurately reflects brain Tdegrees, NP Tdegrees is a safe surrogate indicator of cooling. During rewarming, all peripheral sites underestimate brain temperature and caution is required to avoid hyperthermic arterial inflow, which may inadvertently, result in brain hyperthermia.
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Shen, Erica Y; Ahern, Todd H; Cheung, Iris; Straubhaar, Juerg; Dincer, Aslihan; Houston, Isaac; de Vries, Geert J; Akbarian, Schahram; Forger, Nancy G
2015-06-01
Many neurological and psychiatric disorders exhibit gender disparities, and sex differences in the brain likely explain some of these effects. Recent work in rodents points to a role for epigenetics in the development or maintenance of neural sex differences, although genome-wide studies have so far been lacking. Here we review the existing literature on epigenetics and brain sexual differentiation and present preliminary analyses on the genome-wide distribution of histone-3 lysine-4 trimethylation in a sexually dimorphic brain region in male and female mice. H3K4me3 is a histone mark primarily organized as 'peaks' surrounding the transcription start site of active genes. We microdissected the bed nucleus of the stria terminalis and preoptic area (BNST/POA) in adult male and female mice and used ChIP-Seq to compare the distribution of H3K4me3 throughout the genome. We found 248 genes and loci with a significant sex difference in H3K4me3. Of these, the majority (71%) had larger H3K4me3 peaks in females. Comparisons with existing databases indicate that genes and loci with increased H3K4me3 in females are associated with synaptic function and with expression atlases from related brain areas. Based on RT-PCR, only a minority of genes with a sex difference in H3K4me3 has detectable sex differences in expression at baseline conditions. Together with previous findings, our data suggest that there may be sex biases in the use of epigenetic marks. Such biases could underlie sex differences in vulnerabilities to drugs or diseases that disrupt specific epigenetic processes. Copyright © 2014 Elsevier Inc. All rights reserved.
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Clinical MRS studies of the brain
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hubesch, B.; Marinier, D.S.; Hetherington, H.P.
1989-12-01
Image-guided {sup 31}P and 1H magnetic resonance localized spectroscopy was performed on patients with brain tumors, temporal lobe epilepsy, chronic brain stroke, and deep white matter lesions. Absolute molar concentrations of metabolites, peak area ratios, and pH were obtained. The important findings were that {sup 31}P metabolite concentrations were significantly reduced in tumors, infarcts, and deep white matter lesions. Similarly, {sup 1}H metabolite intensities were reduced in chronic stroke. In the seizure foci of epilepsy patients, in tumors, and in chronic stroke, the pH was more alkaline than the normal pH. Peak area ratios were altered in tumors (reduction ofmore » phosphocreatine/inorganic phosphate) and in chronic stroke (large increases in Cr/NAA and Cho/NAA). Finally, the spectroscopic imaging technique offers a versatile alternative to the single point techniques, producing spectra or images of the spatial distribution of individual {sup 31}P metabolites.« less
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Concussion classification via deep learning using whole-brain white matter fiber strains
Cai, Yunliang; Wu, Shaoju; Zhao, Wei; Li, Zhigang; Wu, Zheyang
2018-01-01
Developing an accurate and reliable injury predictor is central to the biomechanical studies of traumatic brain injury. State-of-the-art efforts continue to rely on empirical, scalar metrics based on kinematics or model-estimated tissue responses explicitly pre-defined in a specific brain region of interest. They could suffer from loss of information. A single training dataset has also been used to evaluate performance but without cross-validation. In this study, we developed a deep learning approach for concussion classification using implicit features of the entire voxel-wise white matter fiber strains. Using reconstructed American National Football League (NFL) injury cases, leave-one-out cross-validation was employed to objectively compare injury prediction performances against two baseline machine learning classifiers (support vector machine (SVM) and random forest (RF)) and four scalar metrics via univariate logistic regression (Brain Injury Criterion (BrIC), cumulative strain damage measure of the whole brain (CSDM-WB) and the corpus callosum (CSDM-CC), and peak fiber strain in the CC). Feature-based machine learning classifiers including deep learning, SVM, and RF consistently outperformed all scalar injury metrics across all performance categories (e.g., leave-one-out accuracy of 0.828–0.862 vs. 0.690–0.776, and .632+ error of 0.148–0.176 vs. 0.207–0.292). Further, deep learning achieved the best cross-validation accuracy, sensitivity, AUC, and .632+ error. These findings demonstrate the superior performances of deep learning in concussion prediction and suggest its promise for future applications in biomechanical investigations of traumatic brain injury. PMID:29795640
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Concussion classification via deep learning using whole-brain white matter fiber strains.
Cai, Yunliang; Wu, Shaoju; Zhao, Wei; Li, Zhigang; Wu, Zheyang; Ji, Songbai
2018-01-01
Developing an accurate and reliable injury predictor is central to the biomechanical studies of traumatic brain injury. State-of-the-art efforts continue to rely on empirical, scalar metrics based on kinematics or model-estimated tissue responses explicitly pre-defined in a specific brain region of interest. They could suffer from loss of information. A single training dataset has also been used to evaluate performance but without cross-validation. In this study, we developed a deep learning approach for concussion classification using implicit features of the entire voxel-wise white matter fiber strains. Using reconstructed American National Football League (NFL) injury cases, leave-one-out cross-validation was employed to objectively compare injury prediction performances against two baseline machine learning classifiers (support vector machine (SVM) and random forest (RF)) and four scalar metrics via univariate logistic regression (Brain Injury Criterion (BrIC), cumulative strain damage measure of the whole brain (CSDM-WB) and the corpus callosum (CSDM-CC), and peak fiber strain in the CC). Feature-based machine learning classifiers including deep learning, SVM, and RF consistently outperformed all scalar injury metrics across all performance categories (e.g., leave-one-out accuracy of 0.828-0.862 vs. 0.690-0.776, and .632+ error of 0.148-0.176 vs. 0.207-0.292). Further, deep learning achieved the best cross-validation accuracy, sensitivity, AUC, and .632+ error. These findings demonstrate the superior performances of deep learning in concussion prediction and suggest its promise for future applications in biomechanical investigations of traumatic brain injury.
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An Animal-to-Human Scaling Law for Blast-Induced Traumatic Brain Injury Risk Assessment
2014-10-28
TERMS b. ABSTRACT 2. REPORT TYPE 17. LIMITATION OF ABSTRACT 15. NUMBER OF PAGES 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 5c...brain, as well as their acoustic impedance. Peak stresses transmitted to the brain tissue by the blast are then shown to be a power function of the...be a power function of the scaling parameter for a range of blast conditions relevant to TBI. In particu- lar, it is found that human brain
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Intraoperative delineation of primary brain tumors using time-resolved fluorescence spectroscopy
Butte, Pramod V.; Fang, Qiyin; Jo, Javier A.; Yong, William H.; Pikul, Brian K.; Black, Keith L.; Marcu, Laura
2010-01-01
The goal of this study is to determine the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as an adjunctive tool for delineation of brain tumor from surrounding normal tissue in order to assist the neurosurgeon in near-complete tumor excision. A time-domain TR-LIFS prototype apparatus (gated photomultiplier detection, fast digitizer) was used for recording tissue autofluorescence in normal cortex (NC), normal white matter (NWM), and various grades of gliomas intraoperatively. Tissue fluorescence was induced with a pulsed nitrogen laser (337nm, 700ps), and the intensity decay profiles were recorded in the 360-to550-nm spectral range (10-nm interval). Histopathological analysis (hematoxylin & eosin) of the biopsy samples taken from the site of TR-LIFS measurements was used for validation of spectroscopic results. Preliminary results on 17 patients demonstrate that normal cortex (N=16) and normal white matter (N=3) show two peaks of fluorescence emission at 390nm(lifetime=1.8±0.3ns) and 460nm(lifetime=0.8±0.1ns). The 390-nm emission peak is absent in low-grade glioma (N=5; lifetime=1.1ns) and reduced in high-grade glioma (N=9; lifetime=1.7±0.4ns). The emission characteristics at 460nm in all tissues correlated with the nicotinamide adenine dinucleotide fluorescence (peak: 440to460nm; lifetime: 0.8to1.0ns). These findings demonstrate the potential of using TR-LIFS as a tool for enhanced delineation of brain tumors during surgery. In addition, this study evaluates similarities and differences between TR-LIFS signatures of brain tumors obtained in vivo and those previously reported in ex vivo brain tumor specimens. PMID:20459282
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Intraoperative delineation of primary brain tumors using time-resolved fluorescence spectroscopy.
Butte, Pramod V; Fang, Qiyin; Jo, Javier A; Yong, William H; Pikul, Brian K; Black, Keith L; Marcu, Laura
2010-01-01
The goal of this study is to determine the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as an adjunctive tool for delineation of brain tumor from surrounding normal tissue in order to assist the neurosurgeon in near-complete tumor excision. A time-domain TR-LIFS prototype apparatus (gated photomultiplier detection, fast digitizer) was used for recording tissue autofluorescence in normal cortex (NC), normal white matter (NWM), and various grades of gliomas intraoperatively. Tissue fluorescence was induced with a pulsed nitrogen laser (337 nm, 700 ps), and the intensity decay profiles were recorded in the 360- to 550-nm spectral range (10-nm interval). Histopathological analysis (hematoxylin & eosin) of the biopsy samples taken from the site of TR-LIFS measurements was used for validation of spectroscopic results. Preliminary results on 17 patients demonstrate that normal cortex (N=16) and normal white matter (N=3) show two peaks of fluorescence emission at 390 nm (lifetime=1.8+/-0.3 ns) and 460 nm (lifetime=0.8+/-0.1 ns). The 390-nm emission peak is absent in low-grade glioma (N=5; lifetime=1.1 ns) and reduced in high-grade glioma (N=9; lifetime=1.7+/-0.4 ns). The emission characteristics at 460 nm in all tissues correlated with the nicotinamide adenine dinucleotide fluorescence (peak: 440 to 460 nm; lifetime: 0.8 to 1.0 ns). These findings demonstrate the potential of using TR-LIFS as a tool for enhanced delineation of brain tumors during surgery. In addition, this study evaluates similarities and differences between TR-LIFS signatures of brain tumors obtained in vivo and those previously reported in ex vivo brain tumor specimens.
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Intraoperative delineation of primary brain tumors using time-resolved fluorescence spectroscopy
NASA Astrophysics Data System (ADS)
Butte, Pramod V.; Fang, Qiyin; Jo, Javier A.; Yong, William H.; Pikul, Brian K.; Black, Keith L.; Marcu, Laura
2010-03-01
The goal of this study is to determine the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as an adjunctive tool for delineation of brain tumor from surrounding normal tissue in order to assist the neurosurgeon in near-complete tumor excision. A time-domain TR-LIFS prototype apparatus (gated photomultiplier detection, fast digitizer) was used for recording tissue autofluorescence in normal cortex (NC), normal white matter (NWM), and various grades of gliomas intraoperatively. Tissue fluorescence was induced with a pulsed nitrogen laser (337 nm, 700 ps), and the intensity decay profiles were recorded in the 360- to 550-nm spectral range (10-nm interval). Histopathological analysis (hematoxylin & eosin) of the biopsy samples taken from the site of TR-LIFS measurements was used for validation of spectroscopic results. Preliminary results on 17 patients demonstrate that normal cortex (N=16) and normal white matter (N=3) show two peaks of fluorescence emission at 390 nm (lifetime=1.8+/-0.3 ns) and 460 nm (lifetime=0.8+/-0.1 ns). The 390-nm emission peak is absent in low-grade glioma (N=5; lifetime=1.1 ns) and reduced in high-grade glioma (N=9; lifetime=1.7+/-0.4 ns). The emission characteristics at 460 nm in all tissues correlated with the nicotinamide adenine dinucleotide fluorescence (peak: 440 to 460 nm lifetime: 0.8 to 1.0 ns). These findings demonstrate the potential of using TR-LIFS as a tool for enhanced delineation of brain tumors during surgery. In addition, this study evaluates similarities and differences between TR-LIFS signatures of brain tumors obtained in vivo and those previously reported in ex vivo brain tumor specimens.
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Fu, Yunfa; Xiong, Xin; Jiang, Changhao; Xu, Baolei; Li, Yongcheng; Li, Hongyi
2017-09-01
Simultaneous acquisition of brain activity signals from the sensorimotor area using NIRS combined with EEG, imagined hand clenching force and speed modulation of brain activity, as well as 6-class classification of these imagined motor parameters by NIRS-EEG were explored. Near infrared probes were aligned with C3 and C4, and EEG electrodes were placed midway between the NIRS probes. NIRS and EEG signals were acquired from six healthy subjects during six imagined hand clenching force and speed tasks involving the right hand. The results showed that NIRS combined with EEG is effective for simultaneously measuring brain activity of the sensorimotor area. The study also showed that in the duration of (0, 10) s for imagined force and speed of hand clenching, HbO first exhibited a negative variation trend, which was followed by a negative peak. After the negative peak, it exhibited a positive variation trend with a positive peak about 6-8 s after termination of imagined movement. During (-2, 1) s, the EEG may have indicated neural processing during the preparation, execution, and monitoring of a given imagined force and speed of hand clenching. The instantaneous phase, frequency, and amplitude feature of the EEG were calculated by Hilbert transform; HbO and the difference between HbO and Hb concentrations were extracted. The features of NIRS and EEG were combined to classify three levels of imagined force [at 20/50/80% MVGF (maximum voluntary grip force)] and speed (at 0.5/1/2 Hz) of hand clenching by SVM. The average classification accuracy of the NIRS-EEG fusion feature was 0.74 ± 0.02. These results may provide increased control commands of force and speed for a brain-controlled robot based on NIRS-EEG.
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[The human electroencephalogram during the mental recall of emotionally colored events].
Kostiunina, M B
1998-01-01
The role of the left and right brain hemispheres in mental reproduction of emotional states by human subjects was analyzed using a new technique of EEG power spectral analysis in narrow frequency bands. At the maximal emotional tension joy was shown to be characterized by an increase in the alpha peak frequency. On the contrary, sorrow accompanied by a decrease in this value. We think that the left hemisphere (as well as the right one) participate in the development of emotional reactions.
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Prediction of individual season of birth using MRI.
Pantazatos, Spiro P
2014-03-01
Previous research suggests statistical associations between season of birth (SOB) with prevalence of neurobehavioral disorders such as schizophrenia and bipolar disorder, personality traits such as novelty and sensation seeking, and suicidal behavior. These effects are thought to be mediated by seasonal differences in perinatal photoperiod, which was recently shown to imprint circadian clock neurons and behavior in rodents. However, it is unknown whether SOB is associated with any measurable differences in the normal human adult brain, and whether individual SOB can be deduced based on phenotype. Here I show that SOB predicts morphological differences in brain structure, and that MRI scans carry spatially distributed information allowing significantly above chance prediction of an individual's SOB. Using an open source database of over 550 structural brain scans, Voxel-Based Morphometry (VBM) analysis showed a significant SOB effect in the left superior temporal gyrus (STG) in males (p=0.009, FWE whole-brain corrected), with greater gray matter volumes in fall and winter births. A cosinor analysis revealed a significant annual periodicity in the left STG gray matter volume (Zero Amplitude Test: p<5×10(-7)), with a peak towards the end of December and a nadir towards the end of June, suggesting that perinatal photoperiod accounts for this SOB effect. Whole-brain VBM maps were used as input features to multivariate machine-learning based analyses to classify SOB. Significantly greater than chance prediction was achieved in females (overall accuracy 35%, p<0.001), but not in males (overall accuracy 26%, p=0.45). Pairwise binary classification in females revealed that the highest discrimination was obtained for winter vs. summer classification (peak area under the ROC curve=0.71, p<0.0005). Discriminating regions included fusiform and middle temporal gyrus, inferior and superior parietal lobe, cerebellum, and dorsolateral and dorsomedial prefrontal cortex. Results indicate that SOB is detectable with MRI, imply that SOB exerts effects on the developing human brain that persist through adulthood, and suggest that neuroimaging may be a valuable intermediate phenotype in bridging the gap between SOB and personality and neurobehavioral disorders. Copyright © 2013 Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Wang, Po-Hsun; Liu, Hao-Li; Hsu, Po-Hung; Lin, Chia-Yu; Chris Wang, Churng-Ren; Chen, Pin-Yuan; Wei, Kuo-Chen; Yen, Tzu-Chen; Li, Meng-Lin
2012-06-01
In this study, we develop a novel photoacoustic imaging technique based on gold nanorods (AuNRs) for quantitatively monitoring focused-ultrasound (FUS) induced blood-brain barrier (BBB) opening in a rat model in vivo. This study takes advantage of the strong near-infrared absorption (peak at ~800 nm) of AuNRs and the extravasation tendency from BBB opening foci due to their nano-scale size to passively label the BBB disruption area. Experimental results show that AuNR contrast-enhanced photoacoustic microscopy (PAM) successfully reveals the spatial distribution and temporal response of BBB disruption area in the rat brains. The quantitative measurement of contrast enhancement has potential to estimate the local concentration of AuNRs and even the dosage of therapeutic molecules when AuNRs are further used as nano-carrier for drug delivery or photothermal therapy. The photoacoustic results also provide complementary information to MRI, being helpful to discover more details about FUS induced BBB opening in small animal models.
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Alcohol ADME in primates studied with positron emission tomography.
Li, Zizhong; Xu, Youwen; Warner, Don; Volkow, Nora D
2012-01-01
The sensitivity to the intoxicating effects of alcohol as well as its adverse medical consequences differ markedly among individuals, which reflects in part differences in alcohol's absorption, distribution, metabolism, and elimination (ADME) properties. The ADME of alcohol in the body and its relationship with alcohol's brain bioavailability, however, is not well understood. The ADME of C-11 labeled alcohol, CH(3) (11)CH(2)OH, 1 and C-11 and deuterium dual labeled alcohol, CH(3) (11)CD(2)OH, 2 in baboons was compared based on the principle that C-D bond is stronger than C-H bond, thus the reaction is slower if C-D bond breaking occurs in a rate-determining metabolic step. The following ADME parameters in peripheral organs and brain were derived from time activity curve (TAC) of positron emission tomography (PET) scans: peak uptake (C(max)); peak uptake time (T(max)), half-life of peak uptake (T(1/2)), the area under the curve (AUC(60 min)), and the residue uptake (C(60 min)). For 1 the highest uptake occurred in the kidney whereas for 2 it occurred in the liver. A deuterium isotope effect was observed in the kidneys in both animals studied and in the liver of one animal but not the other. The highest uptake for 1 and 2 in the brain was in striatum and cerebellum but 2 had higher uptake than 1 in all brain regions most evidently in thalamus and cingulate. Alcohol's brain uptake was significantly higher when given intravenously than when given orally and also when the animal was pretreated with a pharmacological dose of alcohol. The study shows that alcohol metabolism in peripheral organs had a large effect on alcohol's brain bioavailability. This study sets the stage for clinical investigation on how genetics, gender and alcohol abuse affect alcohol's ADME and its relationship to intoxication and medical consequences.
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Emerging Viral Infections in Sub-Saharan Africa and the Developing Nervous System: A Mini Review.
Kakooza-Mwesige, Angelina; Mohammed, Abdul H; Kristensson, Krister; Juliano, Sharon L; Lutwama, Julius J
2018-01-01
The global public health concern is heightened over the increasing number of emerging viruses, i.e., newly discovered or previously known that have expanded into new geographical zones. These viruses challenge the health-care systems in sub-Saharan Africa (SSA) countries from which several of them have originated and been transmitted by insects worldwide. Some of these viruses are neuroinvasive, but have been relatively neglected by neuroscientists. They may provide experiments by nature to give a time window for exposure to a new virus within sizeable, previously non-infected human populations, which, for instance, enables studies on potential long-term or late-onset effects on the developing nervous system. Here, we briefly summarize studies on the developing brain by West Nile, Zika, and Chikungunya viruses, which are mosquito-borne and have spread worldwide out of SSA. They can all be neuroinvasive, but their effects vary from malformations caused by prenatal infections to cognitive disturbances following perinatal or later infections. We also highlight Ebola virus, which can leave surviving children with psychiatric disturbances and cause persistent infections in the non-human primate brain. Greater awareness within the neuroscience community is needed to emphasize the menace evoked by these emerging viruses to the developing brain. In particular, frontline neuroscience research should include neuropediatric follow-up studies in the field on long-term or late-onset cognitive and behavior disturbances or neuropsychiatric disorders. Studies on pathogenetic mechanisms for viral-induced perturbations of brain maturation should be extended to the vulnerable periods when neurocircuit formations are at peaks during infancy and early childhood.
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Emerging Viral Infections in Sub-Saharan Africa and the Developing Nervous System: A Mini Review
Kakooza-Mwesige, Angelina; Mohammed, Abdul H.; Kristensson, Krister; Juliano, Sharon L.; Lutwama, Julius J.
2018-01-01
The global public health concern is heightened over the increasing number of emerging viruses, i.e., newly discovered or previously known that have expanded into new geographical zones. These viruses challenge the health-care systems in sub-Saharan Africa (SSA) countries from which several of them have originated and been transmitted by insects worldwide. Some of these viruses are neuroinvasive, but have been relatively neglected by neuroscientists. They may provide experiments by nature to give a time window for exposure to a new virus within sizeable, previously non-infected human populations, which, for instance, enables studies on potential long-term or late-onset effects on the developing nervous system. Here, we briefly summarize studies on the developing brain by West Nile, Zika, and Chikungunya viruses, which are mosquito-borne and have spread worldwide out of SSA. They can all be neuroinvasive, but their effects vary from malformations caused by prenatal infections to cognitive disturbances following perinatal or later infections. We also highlight Ebola virus, which can leave surviving children with psychiatric disturbances and cause persistent infections in the non-human primate brain. Greater awareness within the neuroscience community is needed to emphasize the menace evoked by these emerging viruses to the developing brain. In particular, frontline neuroscience research should include neuropediatric follow-up studies in the field on long-term or late-onset cognitive and behavior disturbances or neuropsychiatric disorders. Studies on pathogenetic mechanisms for viral-induced perturbations of brain maturation should be extended to the vulnerable periods when neurocircuit formations are at peaks during infancy and early childhood. PMID:29527187
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Skiöld, Béatrice; Wu, Qizhu; Hooper, Stuart B.; Davis, Peter G.; McIntyre, Richard; Tolcos, Mary; Pearson, James; Vreys, Ruth; Egan, Gary F.; Barton, Samantha K.; Cheong, Jeanie L. Y.; Polglase, Graeme R.
2014-01-01
Background and Aim High tidal volume (VT) ventilation during resuscitation of preterm lambs results in brain injury evident histologically within hours after birth. We aimed to investigate whether magnetic resonance spectroscopy (MRS) and/or diffusion tensor imaging (DTI) can be used for early in vivo detection of ventilation-induced brain injury in preterm lambs. Methods Newborn lambs (0.85 gestation) were stabilized with a “protective ventilation” strategy (PROT, n = 7: prophylactic Curosurf, sustained inflation, VT 7 mL/kg, positive end expiratory pressure (PEEP) 5 cmH2O) or an initial 15 minutes of “injurious ventilation” (INJ, n = 10: VT 12 mL/kg, no PEEP, late Curosurf) followed by PROT ventilation for the remainder of the experiment. At 1 hour, lambs underwent structural magnetic resonance imaging (Siemens, 3 Tesla). For measures of mean/axial/radial diffusivity (MD, AD, RD) and fractional anisotropy (FA), 30 direction DTI was performed. Regions of interests encompassed the thalamus, internal capsule, periventricular white matter and the cerebellar vermis. MRS was performed using a localized single-voxel (15×15×20 mm3, echo time 270 ms) encompassing suptratentorial deep nuclear grey matter and central white matter. Peak-area ratios for lactate (Lac) relative to N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were calculated. Groups were compared using 2-way RM-ANOVA, Mann-Whitney U-test and Spearman's correlations. Results No cerebral injury was seen on structural MR images. Lambs in the INJ group had higher mean FA and lower mean RD in the thalamus compared to PROT lambs, but not in the other regions of interest. Peak-area lactate ratios >1.0 was only seen in INJ lambs. A trend of higher mean peak-area ratios for Lac/Cr and Lac/Cho was seen, which correlated with lower pH in both groups. Conclusion Acute changes in brain diffusion measures and metabolite peak-area ratios were observed after injurious ventilation. Early MRS/DTI is able to detect the initiation of ventilation-induced brain injury. PMID:24759765
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Solomon, Irene C; Chon, Ki H; Rodriguez, Melissa N
2003-01-01
Recent investigations have examined the influence of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in vitro using transverse medullary slice and en bloc brain stem-spinal cord preparations obtained from neonatal (1-5 days postnatal) mice. Gap junction proteins, however, have been identified in both neurons and glia in brain stem regions implicated in respiratory control in both neonatal and adult rodents. Here, we used an in vitro arterially perfused rat preparation to examine the role of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents. We recorded rhythmic inspiratory motor activity from one or both phrenic nerves before and during pharmacological blockade (i.e., uncoupling) of brain stem gap junctions using carbenoxolone (100 microM), 18alpha-glycyrrhetinic acid (25-100 microM), 18beta-glycyrrhetinic acid (25-100 microM), octanol (200-300 microM), or heptanol (200 microM). During perfusion with a gap junction uncoupling agent, we observed an increase in the frequency of phrenic bursts (~95% above baseline frequency; P < 0.001) and a decrease in peak amplitude of integrated phrenic nerve discharge (P < 0.001). The increase in frequency of phrenic bursts resulted from a decrease in both T(I) (P < 0.01) and T(E) (P < 0.01). In addition, the pattern of phrenic nerve discharge shifted from an augmenting discharge pattern to a "bell-shaped" or square-wave discharge pattern in most experiments. Spectral analyses using a fast Fourier transform (FFT) algorithm revealed a reduction in the peak power of both the 40- to 50-Hz peak (corresponding to the MFO) and 90- to 110-Hz peak (corresponding to the HFO) although spurious higher frequency activity (> or =130 Hz) was observed, suggesting an overall loss or reduction in inspiratory-phase synchronization. Although additional experiments are required to identify the specific brain stem regions and cell types (i.e., neurons, glia) mediating the observed modulations in phrenic motor output, these findings suggest that gap junction communication modulates generation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents in vitro.
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Elkin, Benjamin S; Gabler, Lee F; Panzer, Matthew B; Siegmund, Gunter P
2018-03-29
On-field football helmet impacts over a large range of severities have caused concussions in some players but not in other players. One possible explanation for this variability is the struck player's helmet impact location. We examined the effect of impact location on regional brain tissue strain when input energy was held constant. Laboratory impacts were performed at 12 locations distributed over the helmet and the resulting head kinematics were simulated in two finite element models of the brain: the Simulated Injury Monitor and the Global Human Body Model Consortium brain model. Peak kinematics, injury metrics and brain strain varied significantly with impact location. Differences in impact location explained 33 to 37% of the total variance in brain strain for the whole brain and cerebrum, considerably more than the variance explained by impact location for the peak resultant head kinematics (8 to 23%) and slightly more than half of the variance explained by the difference in closing speed (57 to 61%). Both finite element models generated similar strain results, with minor variations for impacts that generated multi-axial rotations, larger variations in brainstem strains for some impact locations and a small bias for the cerebellum. Based on this experimental and computational simulation study, impact location on the football helmet has a large effect on regional brain tissue strain. We also found that the lowest strains consistently occurred in impacts to the crown and forehead, helmet locations commonly associated with the striking player. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Evans, R Douglas; Hickie, Brendan; Rouvinen-Watt, Kirsti; Wang, Wei
2016-03-01
Despite the importance of methylmercury (MeHg) as a neurotoxin, we have relatively few good data on partitioning and kinetics of MeHg among organs, particularly across the blood-brain barrier, for mammals that consume large quantities of fish. The objective of this study was to determine the partition coefficients between blood and brain, liver and kidney and fur for MeHg under steady-state conditions and to measure the half-lives for MeHg in these organs. Captive mink (Neovison vison) were fed a diet enriched with two stable isotopes of Hg, Me(199)Hg and Me(201)Hg for a period of 60 days. After a period of 10 days the diet was changed to contain only Me(201)Hg so that, between days 10 and 60, we were able to measure both uptake and elimination rates from blood, brain, liver kidney and fur. Liver and kidney response was very rapid, closely following changes in blood concentrations but there was a small lag time between peak blood concentrations and peak brain concentrations. Half-lives for MeHg were 15.4, 10.2 and 13.4 days for brain, liver and kidney, respectively. There was no measurable conversion of the MeHg to inorganic Hg (IHg) in the brain over the 60 day period, unlike in liver and kidney. Copyright © 2016 Elsevier B.V. All rights reserved.
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Sun, Xiao-Cai; Xian, Xiao-Hui; Li, Wen-Bin; Li, Li; Yan, Cai-Zhen; Li, Qing-Jun; Zhang, Min
2010-08-01
This study investigates whether activation of p38 MAPK by the up-regulation of HSP 70 participates in the induction of brain ischemic tolerance by limb ischemic preconditioning (LIP). Western blot and immunohistochemical assays indicated that p38 MAPK activation occurred earlier than HSP 70 induction in the CA1 region of the hippocampus after LIP. P-p38 MAPK expression was up-regulated at 6h and reached its peak 12h after LIP, while HSP 70 expression was not significantly increased until 1 day and peaked 2 days after LIP. Neuropathological evaluation by thionin staining showed that quercetin (4 ml/kg, 50mg/kg, intraperitoneal injection), an inhibitor of HSP 70, blocked the protective effect of LIP against delayed neuronal death that is normally induced by lethal brain ischemic insult, indicating that HSP 70 participates in the induction of brain ischemic tolerance by LIP. Furthermore, SB 203580, an inhibitor of HSP 70, inhibited HSP 70 activation in the CA1 region of the hippocampus induced by LIP either with or without the presence of subsequent brain ischemic insult. Based on the above results, it can be concluded that activation of p38 MAPK participates in the brain ischemic tolerance induced by LIP at least partly by the up-regulation of HSP 70 expression. (c) 2010 Elsevier Inc. All rights reserved.
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Zhang, Jiaxing; Zhang, Haiyan; Chen, Ji; Fan, Ming; Gong, Qiyong
2013-01-01
The present study aimed to investigate structural modulation of brain by high level of oxygen during its peak period of development. Voxel-based morphometry analysis of gray matter (GM) and white matter (WM) volumes and Tract-Based Spatial Statistics analysis of WM fractional anisotropy (FA) and mean diffusion (MD) based on MRI images were carried out on 21 Tibetan adolencents (15-18 years), who were born and raised in Qinghai-Tibetan Plateau (2900-4700 m) and have lived at sea level (SL) in the last 4 years. The control group consisted of matched Tibetan adolescents born and raised at high altitude all the time. SL immigrants had increased GM volume in the left insula, left inferior parietal gyrus, and right superior parietal gyrus and decreased GM in the left precentral cortex and multiple sites in cerebellar cortex (left lobule 8, bilateral lobule 6 and crus 1/2). Decreased WM volume was found in the right superior frontal gyrus in SL immigrants. SL immigrants had higher FA and lower MD at multiple sites of WM tracts. Moreover, we detected changes in ventilation and circulation. GM volume in cerebellum lobule 8 positively correlated with diastolic pressure, while GM volume in insula positively correlated vital capacity and hypoxic ventilatory response. Our finding indicate that the structural modulations of GM by high level of oxygen during its peak period of development are related to respiratory and circulatory regulations, while the modulation in WM mainly exhibits an enhancement in myelin maturation.
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A longitudinal study of auditory evoked field and language development in young children.
Yoshimura, Yuko; Kikuchi, Mitsuru; Ueno, Sanae; Shitamichi, Kiyomi; Remijn, Gerard B; Hiraishi, Hirotoshi; Hasegawa, Chiaki; Furutani, Naoki; Oi, Manabu; Munesue, Toshio; Tsubokawa, Tsunehisa; Higashida, Haruhiro; Minabe, Yoshio
2014-11-01
The relationship between language development in early childhood and the maturation of brain functions related to the human voice remains unclear. Because the development of the auditory system likely correlates with language development in young children, we investigated the relationship between the auditory evoked field (AEF) and language development using non-invasive child-customized magnetoencephalography (MEG) in a longitudinal design. Twenty typically developing children were recruited (aged 36-75 months old at the first measurement). These children were re-investigated 11-25 months after the first measurement. The AEF component P1m was examined to investigate the developmental changes in each participant's neural brain response to vocal stimuli. In addition, we examined the relationships between brain responses and language performance. P1m peak amplitude in response to vocal stimuli significantly increased in both hemispheres in the second measurement compared to the first measurement. However, no differences were observed in P1m latency. Notably, our results reveal that children with greater increases in P1m amplitude in the left hemisphere performed better on linguistic tests. Thus, our results indicate that P1m evoked by vocal stimuli is a neurophysiological marker for language development in young children. Additionally, MEG is a technique that can be used to investigate the maturation of the auditory cortex based on auditory evoked fields in young children. This study is the first to demonstrate a significant relationship between the development of the auditory processing system and the development of language abilities in young children. Copyright © 2014 Elsevier Inc. All rights reserved.
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Preprotachykinin A mRNA expression in the rat brain during development.
Brené, S; Lindefors, N; Friedman, W J; Persson, H
1990-12-15
Expression of preprotachykinin A (PPT-A) mRNA was analyzed by northern blots using mRNA prepared from rat brain at 12 different developmental stages ranging from embryonic day 15 (E15) to adult. A single PPT-A mRNA of 1.3 kb was detected throughout development. PPT-A mRNA was detected as early as E15 and an approximately 3-fold increase occurred at birth. This amount remained until 3 weeks of age when the level increased, reaching a peak at 5 weeks of age. Adult amounts were approximately 3-fold higher than the levels at birth. The distribution of PPT-A mRNA-expressing cells in rat brain was studied by in situ hybridization on sections from embryonic day 20, postnatal days 4 and 7 as well as adult. Cells expressing PPT-A mRNA were detected in the forebrain at all 4 ages analyzed. However, the hybridization pattern and the labeling intensity varied in different brain regions during development. In cingulate cortex, intense labeling was seen in numerous cells at embryonic day 20 and postnatal days 4 and 7, whereas in the adult cingulate cortex only a few scattered labeled cells were observed. In frontoparietal cortex labeled cells were found from postnatal day 4 to adult, with the highest density of labeled cells at P7. Developmental differences in both the distribution of PPT-A mRNA-expressing cells and the level of PPT-A mRNA expression were also found in caudate-putamen, lateral hypothalamus and amygdala. Thus, our results show several changes in PPT-A mRNA expression during ontogeny, indicating a region and time-specific regulation of PPT-A mRNA expression during brain maturation.
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Thomas, Jennifer D; Abou, Elizabeth J; Dominguez, Hector D
2009-01-01
Prenatal alcohol exposure can lead to a range of physical, neurological, and behavioral alterations referred to as fetal alcohol spectrum disorders (FASD). Variability in outcome observed among children with FASD is likely related to various pre- and postnatal factors, including nutritional variables. Choline is an essential nutrient that influences brain and behavioral development. Recent animal research indicates that prenatal choline supplementation leads to long-lasting cognitive enhancement, as well as changes in brain morphology, electrophysiology and neurochemistry. The present study examined whether choline supplementation during ethanol exposure effectively reduces fetal alcohol effects. Pregnant dams were exposed to 6.0g/kg/day ethanol via intubation from gestational days (GD) 5-20; pair-fed and lab chow controls were included. During treatment, subjects from each group received choline chloride (250mg/kg/day) or vehicle. Physical development and behavioral development (righting reflex, geotactic reflex, cliff avoidance, reflex suspension and hindlimb coordination) were examined. Subjects prenatally exposed to alcohol exhibited reduced birth weight and brain weight, delays in eye opening and incisor emergence, and alterations in the development of all behaviors. Choline supplementation significantly attenuated ethanol's effects on birth and brain weight, incisor emergence, and most behavioral measures. In fact, behavioral performance of ethanol-exposed subjects treated with choline did not differ from that of controls. Importantly, choline supplementation did not influence peak blood alcohol level or metabolism, indicating that choline's effects were not due to differential alcohol exposure. These data indicate early dietary supplements may reduce the severity of some fetal alcohol effects, findings with important implications for children of women who drink alcohol during pregnancy.
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Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice.
Neumann, Inga D; Maloumby, Rodrigue; Beiderbeck, Daniela I; Lukas, Michael; Landgraf, Rainer
2013-10-01
The possibility to improve socio-emotional behaviors in humans by intranasal administration of synthetic oxytocin (OXT) attracts increasing attention, but its uptake into the brain has never been demonstrated so far. Here we used simultaneous microdialysis in both the dorsal hippocampus and amygdala of rats and mice in combination with concomitant blood sampling from the jugular vein to study the dynamics of the neuropeptide in brain extracellular fluid and plasma after its nasal administration. OXT was found to be increased in microdialysates from both the hippocampus and amygdala with peak levels occurring 30-60min after nasal administration. Despite a similar temporal profile of OXT concentrations in plasma, peripheral OXT is unlikely to contribute to dialysate OXT as calculated from in vitro recovery data, indicating a central route of transport. Moreover, intraperitoneal administration of synthetic OXT in identical amounts caused rapid peak levels in brain dialysates and plasma during the first 30min after treatment and a subsequent return toward baseline. While the precise route(s) of central transport remain to be elucidated, our data provide the first evidence that nasally applied OXT indeed reaches behaviorally relevant brain areas, and this uptake is paralleled by changes in plasma OXT. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Caspase 7: increased expression and activation after traumatic brain injury in rats.
Larner, Stephen F; McKinsey, Deborah M; Hayes, Ronald L; W Wang, Kevin K
2005-07-01
Caspases, a cysteine proteinase family, are required for the initiation and execution phases of apoptosis. It has been suggested that caspase 7, an apoptosis executioner implicated in cell death proteolysis, is redundant to the main executioner caspase 3 and it is generally believed that it is not present in the brain or present in only minute amounts with highly restricted activity. Here we report evidence that caspase 7 is up-regulated and activated after traumatic brain injury (TBI) in rats. TBI disrupts homeostasis resulting in pathological apoptotic activation. After controlled cortical impact TBI of adult male rats we observed, by semiquantitative real-time PCR, increased mRNA levels within the traumatized cortex and hippocampus peaking in the former about 5 days post-injury and in the latter within 6-24 h of trauma. The activation of caspase 7 protein after TBI, demonstrated by immunoblot by the increase of the active form of caspase 7 peaking 5 days post-injury in the cortex and hippocampus, was found to be up-regulated in both neurons and astrocytes by immunohistochemistry. These findings, the first to document the up-regulation of caspase 7 in the brain after acute brain injury in rats, suggest that caspase 7 activation could contribute to neuronal cell death on a scale not previously recognized.
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Li, Zhiqiang; Shu, Qingming; Li, Lingzhi; Ge, Maolin; Zhang, Yongliang
2014-01-01
Traumatic brain injury causes gene expression changes in different brain regions. Occurrence and development of traumatic brain injury are closely related, involving expression of three factors, namely cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. However, little is known about the correlation of these three factors and brain neuronal injury. In this study, primary cultured rat hippocampal neurons were subjected to fluid percussion injury according to Scott's method, with some modifications. RT-PCR and semi-quantitative immunocytochemical staining was used to measure the expression levels of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. Our results found that cyclooxygenase-2 expression were firstly increased post-injury, and then decreased. Both mRNA and protein expression levels reached peaks at 8 and 12 hours post-injury, respectively. Similar sequential changes in glutamate receptor 2 were observed, with highest levels mRNA and protein expression at 8 and 12 hours post-injury respectively. On the contrary, the expressions of platelet activating factor receptor were firstly decreased post-injury, and then increased. Both mRNA and protein expression levels reached the lowest levels at 8 and 12 hours post-injury, respectively. Totally, our findings suggest that these three factors are involved in occurrence and development of hippocampal neuronal injury. PMID:25206921
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Demanuele, Charmaine; James, Christopher J; Sonuga-Barke, Edmund Js
2007-12-10
It has been acknowledged that the frequency spectrum of measured electromagnetic (EM) brain signals shows a decrease in power with increasing frequency. This spectral behaviour may lead to difficulty in distinguishing event-related peaks from ongoing brain activity in the electro- and magnetoencephalographic (EEG and MEG) signal spectra. This can become an issue especially in the analysis of low frequency oscillations (LFOs) - below 0.5 Hz - which are currently being observed in signal recordings linked with specific pathologies such as epileptic seizures or attention deficit hyperactivity disorder (ADHD), in sleep studies, etc. In this work we propose a simple method that can be used to compensate for this 1/f trend hence achieving spectral normalisation. This method involves filtering the raw measured EM signal through a differentiator prior to further data analysis. Applying the proposed method to various exemplary datasets including very low frequency EEG recordings, epileptic seizure recordings, MEG data and Evoked Response data showed that this compensating procedure provides a flat spectral base onto which event related peaks can be clearly observed. Findings suggest that the proposed filter is a useful tool for the analysis of physiological data especially in revealing very low frequency peaks which may otherwise be obscured by the 1/f spectral activity inherent in EEG/MEG recordings.
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Smith, James Evan; Peterchev, Angel V
2018-06-22
Sham TMS coils isolate the ancillary effects of their active counterparts, but typically induce low-strength electric fields (E-fields) in the brain, which could be biologically active. We measured the E-fields induced by two pairs of commonly-used commercial active/sham coils. Approach: E-field distributions of the active and sham configurations of the Magstim 70 mm AFC and MagVenture Cool-B65 A/P coils were measured over a 7-cm-radius, hemispherical grid approximating the cortical surface. Peak E-field strength was recorded over a range of pulse amplitudes. Main results: The Magstim and MagVenture shams induce peak E-fields corresponding to 25.3% and 7.72% of their respective active values. The MagVenture sham has an E-field distribution shaped like its active counterpart. The Magstim sham induces nearly zero E-field under the coil's center, and its peak E-field forms a diffuse oval 3-7 cm from the center. Electrical scalp stimulation paired with the MagVenture sham is estimated to increase the sham E-field in the brain up to 10%. Significance: Different commercial shams induce different E-field strengths and distributions in the brain, which should be considered in interpreting outcomes of sham stimulation. © 2018 IOP Publishing Ltd.
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Eide, Per Kristian; Vatnehol, Svein Are Sirirud; Emblem, Kyrre Eeg; Ringstad, Geir
2018-05-08
Pre-clinical research in rodents provides evidence that the central nervous system (CNS) has functional lymphatic vessels. In-vivo observations in humans, however, are not demonstrated. We here show data on CNS lymphatic drainage to cervical lymph nodes in-vivo by magnetic resonance imaging (MRI) enhanced with an intrathecal contrast agent as a cerebrospinal fluid (CSF) tracer. Standardized MRI of the intracranial compartment and the neck were acquired before and up to 24-48 hours following intrathecal contrast agent administration in 19 individuals. Contrast enhancement was radiologically confirmed by signal changes in CSF nearby inferior frontal gyrus, brain parenchyma of inferior frontal gyrus, parahippocampal gyrus, thalamus and pons, and parenchyma of cervical lymph node, and with sagittal sinus and neck muscle serving as reference tissue for cranial and neck MRI acquisitions, respectively. Time series of changes in signal intensity shows that contrast enhancement within CSF precedes glymphatic enhancement and peaks at 4-6 hours following intrathecal injection. Cervical lymph node enhancement coincides in time with peak glymphatic enhancement, with peak after 24 hours. Our findings provide in-vivo evidence of CSF tracer drainage to cervical lymph nodes in humans. The time course of lymph node enhancement coincided with brain glymphatic enhancement rather than with CSF enhancement.
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Developmental changes in the structure of the social brain in late childhood and adolescence.
Mills, Kathryn L; Lalonde, François; Clasen, Liv S; Giedd, Jay N; Blakemore, Sarah-Jayne
2014-01-01
Social cognition provides humans with the necessary skills to understand and interact with one another. One aspect of social cognition, mentalizing, is associated with a network of brain regions often referred to as the 'social brain.' These consist of medial prefrontal cortex [medial Brodmann Area 10 (mBA10)], temporoparietal junction (TPJ), posterior superior temporal sulcus (pSTS) and anterior temporal cortex (ATC). How these specific regions develop structurally across late childhood and adolescence is not well established. This study examined the structural developmental trajectories of social brain regions in the longest ongoing longitudinal neuroimaging study of human brain maturation. Structural trajectories of grey matter volume, cortical thickness and surface area were analyzed using surface-based cortical reconstruction software and mixed modeling in a longitudinal sample of 288 participants (ages 7-30 years, 857 total scans). Grey matter volume and cortical thickness in mBA10, TPJ and pSTS decreased from childhood into the early twenties. The ATC increased in grey matter volume until adolescence and in cortical thickness until early adulthood. Surface area for each region followed a cubic trajectory, peaking in early or pre-adolescence before decreasing into the early twenties. These results are discussed in the context of developmental changes in social cognition across adolescence.
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Blüml, Stefan; Wisnowski, Jessica L.; Nelson, Marvin D.; Paquette, Lisa; Gilles, Floyd H.; Kinney, Hannah C.; Panigrahy, Ashok
2013-01-01
Between birth and late adolescence, the human brain undergoes exponential maturational changes. Using in vivo magnetic resonance spectroscopy, we determined the developmental profile for 6 metabolites in 5 distinct brain regions based on spectra from 309 children from 0 to 18 years of age. The concentrations of N-acetyl-aspartate (an indicator for adult-type neurons and axons), creatine (energy metabolite), and glutamate (excitatory neurotransmitter) increased rapidly between birth and 3 months, a period of rapid axonal growth and synapse formation. Myo-inositol, implicated in cell signaling and a precursor of membrane phospholipid, as well as an osmolyte and astrocyte marker, declined rapidly during this period. Choline, a membrane metabolite and indicator for de novo myelin and cell membrane synthesis, peaked from birth until approximately 3 months, and then declined gradually, reaching a plateau at early childhood. Similarly, taurine, involved in neuronal excitability, synaptic potentiation, and osmoregulation, was high until approximately 3 months and thereafter declined. These data indicate that the first 3 months of postnatal life are a critical period of rapid metabolic changes in the development of the human brain. This study of the developmental profiles of the major brain metabolites provides essential baseline information for future analyses of the pediatric health and disease. PMID:22952278
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Kreisl, William C; Bhatia, Ritwik; Morse, Cheryl L; Woock, Alicia E; Zoghbi, Sami S; Shetty, H Umesha; Pike, Victor W; Innis, Robert B
2015-01-01
The permeability-glycoprotein (P-gp) efflux transporter is densely expressed at the blood-brain barrier, and its resultant spare capacity requires substantial blockade to increase the uptake of avid substrates, blunting the ability of investigators to measure clinically meaningful alterations in P-gp function. This study, conducted in humans, examined 2 P-gp inhibitors (tariquidar, a known inhibitor, and disulfiram, a putative inhibitor) and 2 routes of administration (intravenous and oral) to maximally increase brain uptake of the avid and selective P-gp substrate (11)C-N-desmethyl-loperamide (dLop) while avoiding side effects associated with high doses of tariquidar. Forty-two (11)C-dLop PET scans were obtained from 37 healthy volunteers. PET was performed with (11)C-dLop under the following 5 conditions: injected under baseline conditions without P-gp inhibition, injected 1 h after intravenous tariquidar infusion, injected during intravenous tariquidar infusion, injected after oral tariquidar, and injected after disulfiram. (11)C-dLop uptake was quantified with kinetic modeling using metabolite-corrected arterial input function or by measuring the area under the time-activity curve in the brain from 10 to 30 min. Neither oral tariquidar nor oral disulfiram increased brain uptake of (11)C-dLop. Injecting (11)C-dLop during tariquidar infusion, when plasma tariquidar concentrations reach their peak, resulted in a brain uptake of the radioligand approximately 5-fold greater than baseline. Brain uptake was similar with 2 and 4 mg of intravenous tariquidar per kilogram; however, the lower dose was better tolerated. Injecting (11)C-dLop after tariquidar infusion also increased brain uptake, though higher doses (up to 6 mg/kg) were required. Brain uptake of (11)C-dLop increased fairly linearly with increasing plasma tariquidar concentrations, but we are uncertain whether maximal uptake was achieved. We sought to increase the dynamic range of P-gp function measured after blockade. Performing (11)C-dLop PET during peak plasma concentrations of tariquidar, achieved with concurrent administration of intravenous tariquidar, resulted in greater P-gp inhibition at the human blood-brain barrier than delayed administration and allowed the use of a lower, more tolerable dose of tariquidar. On the basis of prior monkey studies, we suspect that plasma concentrations of tariquidar did not fully block P-gp; however, higher doses of tariquidar would likely be associated with unacceptable side effects. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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Brain representations for acquiring and recalling visual-motor adaptations
Bédard, Patrick; Sanes, Jerome N.
2014-01-01
Humans readily learn and remember new motor skills, a process that likely underlies adaptation to changing environments. During adaptation, the brain develops new sensory-motor relationships, and if consolidation occurs, a memory of the adaptation can be retained for extended periods. Considerable evidence exists that multiple brain circuits participate in acquiring new sensory-motor memories, though the networks engaged in recalling these and whether the same brain circuits participate in their formation and recall has less clarity. To address these issues, we assessed brain activation with functional MRI while young healthy adults learned and recalled new sensory-motor skills by adapting to world-view rotations of visual feedback that guided hand movements. We found cerebellar activation related to adaptation rate, likely reflecting changes related to overall adjustments to the visual rotation. A set of parietal and frontal regions, including inferior and superior parietal lobules, premotor area, supplementary motor area and primary somatosensory cortex, exhibited non-linear learning-related activation that peaked in the middle of the adaptation phase. Activation in some of these areas, including the inferior parietal lobule, intra-parietal sulcus and somatosensory cortex, likely reflected actual learning, since the activation correlated with learning after-effects. Lastly, we identified several structures having recall-related activation, including the anterior cingulate and the posterior putamen, since the activation correlated with recall efficacy. These findings demonstrate dynamic aspects of brain activation patterns related to formation and recall of a sensory-motor skill, such that non-overlapping brain regions participate in distinctive behavioral events. PMID:25019676
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The influence of acceleration loading curve characteristics on traumatic brain injury.
Post, Andrew; Blaine Hoshizaki, T; Gilchrist, Michael D; Brien, Susan; Cusimano, Michael D; Marshall, Shawn
2014-03-21
To prevent brain trauma, understanding the mechanism of injury is essential. Once the mechanism of brain injury has been identified, prevention technologies could then be developed to aid in their prevention. The incidence of brain injury is linked to how the kinematics of a brain injury event affects the internal structures of the brain. As a result it is essential that an attempt be made to describe how the characteristics of the linear and rotational acceleration influence specific traumatic brain injury lesions. As a result, the purpose of this study was to examine the influence of the characteristics of linear and rotational acceleration pulses and how they account for the variance in predicting the outcome of TBI lesions, namely contusion, subdural hematoma (SDH), subarachnoid hemorrhage (SAH), and epidural hematoma (EDH) using a principal components analysis (PCA). Monorail impacts were conducted which simulated falls which caused the TBI lesions. From these reconstructions, the characteristics of the linear and rotational acceleration were determined and used for a PCA analysis. The results indicated that peak resultant acceleration variables did not account for any of the variance in predicting TBI lesions. The majority of the variance was accounted for by duration of the resultant and component linear and rotational acceleration. In addition, the components of linear and rotational acceleration characteristics on the x, y, and z axes accounted for the majority of the remainder of the variance after duration. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Effect of respiratory and cardiac gating on the major diffusion-imaging metrics.
Hamaguchi, Hiroyuki; Tha, Khin Khin; Sugimori, Hiroyuki; Nakanishi, Mitsuhiro; Nakagawa, Shin; Fujiwara, Taro; Yoshida, Hirokazu; Takamori, Sayaka; Shirato, Hiroki
2016-08-01
The effect of respiratory gating on the major diffusion-imaging metrics and that of cardiac gating on mean kurtosis (MK) are not known. For evaluation of whether the major diffusion-imaging metrics-MK, fractional anisotropy (FA), and mean diffusivity (MD) of the brain-varied between gated and non-gated acquisitions, respiratory-gated, cardiac-gated, and non-gated diffusion-imaging of the brain were performed in 10 healthy volunteers. MK, FA, and MD maps were constructed for all acquisitions, and the histograms were constructed. The normalized peak height and location of the histograms were compared among the acquisitions by use of Friedman and post hoc Wilcoxon tests. The effect of the repetition time (TR) on the diffusion-imaging metrics was also tested, and we corrected for its variation among acquisitions, if necessary. The results showed a shift in the peak location of the MK and MD histograms to the right with an increase in TR (p ≤ 0.01). The corrected peak location of the MK histograms, the normalized peak height of the FA histograms, the normalized peak height and the corrected peak location of the MD histograms varied significantly between the gated and non-gated acquisitions (p < 0.05). These results imply an influence of respiration and cardiac pulsation on the major diffusion-imaging metrics. The gating conditions must be kept identical if reproducible results are to be achieved. © The Author(s) 2016.
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Brusov, O S; Matveev, I A; Kirillov, P S; Faktor, M I; Karpova, N S; Vasilyeva, E F; Katasonov, A B; Zozulya, S A; Klushnik, T P
To assess the risk of thrombotic events in patients with schizophrenia and schizoaffective disorder based on 'fibrinodynamics' technology. A group of 76 women, including 38 with paranoid schizophrenia (F20.0), 18 with schizoaffective disorder (F25.1) in the acute stage, and 20 healthy controls, participated in the study. The technology includes the study of coagulation and fibrinolysis, Karmin author software, and calculation of peak time and hemostasis potential of spontaneous clots. Growth and lysis of fibrin clots were studied in plasma purified from platelets. All preanalytic procedures were conducted within 30 minutes after blood sampling. Blood serum was studied separately using the neuroimmunological test. Dynamic of brightness profiles of the clots was determined and a number of parameters (peak time and hemostasis potential of spontaneous clots) were calculated using the Karmin software. In patients with schizophrenia, the dynamic brightness profile of the clots has two peaks: the first peak is formed as a result of the growth and lysis of the clot initiated by the activator, the second peak is due to the growth and lysis of spontaneous clots in the volume of the measuring cuvette far from the activator. In healthy donors, the second peak under experimental conditions is absent. In the group of schizophrenic patients, a strong negative correlation is observed between the peak time of the second peak and the activity of leukocyte elastase (Spearman R = -0.75, p<0.0001), i.e. the greater the activity of elastase, the earlier the maximum of the second peak is formed and vice versa. In the control group, there is no such correlation. Evaluation of the potential of hemostasis of spontaneous clots showed that in 42% of schizophrenic patients this parameter is shifted above the norm, which indicates an increased risk of thrombosis of small brain arteries in these patients. The developed technology of 'fibrinodynamics' has a good potential for introduction into personalized medicine to identify increased risks of thrombosis of small cerebral vessels in patients with acute schizophrenia leading to the development of cognitive disorders and to control the normalization of hemostasis with antiplatelet or anticoagulant drugs.
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Development of modularity in the neural activity of childrenʼs brains
NASA Astrophysics Data System (ADS)
Chen, Man; Deem, Michael W.
2015-02-01
We study how modularity of the human brain changes as children develop into adults. Theory suggests that modularity can enhance the response function of a networked system subject to changing external stimuli. Thus, greater cognitive performance might be achieved for more modular neural activity, and modularity might likely increase as children develop. The value of modularity calculated from functional magnetic resonance imaging (fMRI) data is observed to increase during childhood development and peak in young adulthood. Head motion is deconvolved from the fMRI data, and it is shown that the dependence of modularity on age is independent of the magnitude of head motion. A model is presented to illustrate how modularity can provide greater cognitive performance at short times, i.e. task switching. A fitness function is extracted from the model. Quasispecies theory is used to predict how the average modularity evolves with age, illustrating the increase of modularity during development from children to adults that arises from selection for rapid cognitive function in young adults. Experiments exploring the effect of modularity on cognitive performance are suggested. Modularity may be a potential biomarker for injury, rehabilitation, or disease.
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Lee, M. C.; O'Neill, J.; Dickenson, A. H.; Iannetti, G. D.
2016-01-01
Central sensitization (CS), the increased sensitivity of the central nervous system to somatosensory inputs, accounts for secondary hyperalgesia, a typical sign of several painful clinical conditions. Brain potentials elicited by mechanical punctate stimulation using flat-tip probes can provide neural correlates of CS, but their signal-to-noise ratio is limited by poor synchronization of the afferent nociceptive input. Additionally, mechanical punctate stimulation does not activate nociceptors exclusively. In contrast, low-intensity intraepidermal electrical stimulation (IES) allows selective activation of type II Aδ-mechano-heat nociceptors (II-AMHs) and elicits reproducible brain potentials. However, it is unclear whether hyperalgesia from IES occurs and coexists with secondary mechanical punctate hyperalgesia, and whether the magnitude of the electroencephalographic (EEG) responses evoked by IES within the hyperalgesic area is increased. To address these questions, we explored the modulation of the psychophysical and EEG responses to IES by intraepidermal injection of capsaicin in healthy human subjects. We obtained three main results. First, the intensity of the sensation elicited by IES was significantly increased in participants who developed robust mechanical punctate hyperalgesia after capsaicin injection (i.e., responders), indicating that hyperalgesia from IES coexists with punctate mechanical hyperalgesia. Second, the N2 peak magnitude of the EEG responses elicited by IES was significantly increased after the intraepidermal injection of capsaicin in responders only. Third, a receiver-operator characteristics analysis showed that the N2 peak amplitude is clearly predictive of the presence of CS. These findings suggest that the EEG responses elicited by IES reflect secondary hyperalgesia and therefore represent an objective correlate of CS. PMID:27098022
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Laterality of Brain Activation for Risk Factors of Addiction
Gordon, Harold W.
2016-01-01
Background: Laterality of brain activation is reported for tests of risk factors of addiction - impulsivity and craving - but authors rarely address the potential significance of those asymmetries. Objective: The purpose of this study is to demonstrate this laterality and discuss its relevance to cognitive and neurophysiological asymmetries associated with drug abuse vulnerability in order to provide new insights for future research in drug abuse. Method: From published reports, brain areas of activation for two tests of response inhibition or craving for drugs of abuse were compiled from fMRI activation peaks and were tabulated for eight sections (octants) in each hemisphere. Percent asymmetries were calculated (R-L/R+L) across studies for each area. Results: For impulsivity, most activation peaks favored the right hemisphere. Overall, the percent difference was 32% (Χ2 = 16.026; p < 0.0001) with the greater asymmetry for anterior peaks (46.8%; Χ2 = 17.329; p < 0.0001). The asymmetries for cue-induced craving were opposite, favoring the left hemisphere by 6.7% (Χ2 = 4.028; p < 0.05). The consistency of left asymmetry was found for almost all drugs. For nicotine, studies where subjects were not allowed to smoke (deprived) prior to measurement had the same left hemisphere activation but those who smoked (satiated) before the fMRI measure showed right asymmetry. Conclusion: Brain activation studies demonstrate different left/right hemispheric contributions for impulsivity versus craving - factors related to addiction. Failure to take laterality into consideration is a missed opportunity in designing studies and gaining insight into the etiology of drug abuse and pathways for treatment. PMID:26674074
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Laterality of Brain Activation for Risk Factors of Addiction.
Gordon, Harold W
2016-01-01
Laterality of brain activation is reported for tests of risk factors of addiction- impulsivity and craving-but authors rarely address the potential significance of those asymmetries. The purpose of this study is to demonstrate this laterality and discuss its relevance to cognitive and neurophysiological asymmetries associated with drug abuse vulnerability in order to provide new insights for future research in drug abuse. From published reports, brain areas of activation for two tests of response inhibition or craving for drugs of abuse were compiled from fMRI activation peaks and were tabulated for eight sections (octants) in each hemisphere. Percent asymmetries were calculated (R-L/R+L) across studies for each area. For impulsivity, most activation peaks favored the right hemisphere. Overall, the percent difference was 32% (Χ2 = 16.026; p < 0.0001) with the greater asymmetry for anterior peaks (46.8%; Χ(2) = 17.329; p < 0.0001). The asymmetries for cue-induced craving were opposite, favoring the left hemisphere by 6.7% (Χ(2) = 4.028; p < 0.05). The consistency of left asymmetry was found for almost all drugs. For nicotine, studies where subjects were not allowed to smoke (deprived) prior to measurement had the same left hemisphere activation but those who smoked (satiated) before the fMRI measure showed right asymmetry. Brain activation studies demonstrate different left/right hemispheric contributions for impulsivity versus craving-factors related to addiction. Failure to take laterality into consideration is a missed opportunity in designing studies and gaining insight into the etiology of drug abuse and pathways for treatment.
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White matter connectivity and aerobic fitness in male adolescents.
Herting, Megan M; Colby, John B; Sowell, Elizabeth R; Nagel, Bonnie J
2014-01-01
Exercise has been shown to have positive effects on the brain and behavior throughout various stages of the lifespan. However, little is known about the impact of exercise on neurodevelopment during the adolescent years, particularly with regard to white matter microstructure, as assessed by diffusion tensor imaging (DTI). Both tract-based spatial statistics (TBSS) and tractography-based along-tract statistics were utilized to examine the relationship between white matter microstructure and aerobic exercise in adolescent males, ages 15-18. Furthermore, we examined the data by both (1) grouping individuals based on aerobic fitness self-reports (high fit (HF) vs. low fit (LF)), and (2) using VO2 peak as a continuous variable across the entire sample. Results showed that HF youth had an overall higher number of streamline counts compared to LF peers, which was driven by group differences in corticospinal tract (CST) and anterior corpus callosum (Fminor). In addition, VO2 peak was negatively related to FA in the left CST. Together, these results suggest that aerobic fitness relates to white matter connectivity and microstructure in tracts carrying frontal and motor fibers during adolescence. Furthermore, the current study highlights the importance of considering the environmental factor of aerobic exercise when examining adolescent brain development. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Portnow, Jana; Badie, Behnam; Chen, Mike; Liu, An; Blanchard, Suzette; Synold, Timothy W.
2010-01-01
Purpose Intracerebral microdialysis (ICMD) is an accepted methodology for monitoring changes in neurochemistry from acute brain injury. The goal of this pilot study was to determine the feasibility of using ICMD to examine the neuropharmacokinetics (nPK) of temozolomide (TMZ) in brain interstitium (BI) following oral administration. Experimental Design Patients with primary or metastatic brain tumors had a microdialysis catheter placed in peritumoral brain tissue at the time of surgical debulking. CT scan confirmed the catheter location. Patients received a single oral dose of TMZ (150 mg/m2) on the first post-operative day, serial plasma and ICMD samples were collected over 24 hrs, and TMZ concentrations were determined by tandem mass spectrometry. Results Nine patients were enrolled. Dialysate and plasma samples were successfully collected from 7 of the 9 patients. The mean TMZ area-under-the-concentration-time-curve (AUC) in plasma and BI were 17.1 and 2.7 μg/ml × hr, with an average BI/plasma AUC ratio of 17.8%. The mean peak TMZ concentration in brain was 0.6 ± 0.3 μg/ml, and the mean time to reach peak level in brain was 2.0 ± 0.8 hrs. Conclusions The use of ICMD to measure the nPK of systemically administered chemotherapy is safe and feasible. Concentrations of TMZ in BI obtained by ICMD are consistent with published data obtained in a pre-clinical ICMD model, as well as from clinical studies of cerebrospinal fluid. However, the delayed time required to achieve maximum TMZ concentrations in brain suggests that current chemoradiation regimens may be improved by administering TMZ 2-3 hours before radiation. PMID:19861433
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NASA Astrophysics Data System (ADS)
Liu, Tuo; Chen, Changshui; Shi, Xingzhe; Liu, Chengyong
2016-05-01
The Raman spectra of tissue of 20 brain tumor patients was recorded using a confocal microlaser Raman spectroscope with 785 nm excitation in vitro. A total of 133 spectra were investigated. Spectra peaks from normal white matter tissue and tumor tissue were analyzed. Algorithms, such as principal component analysis, linear discriminant analysis, and the support vector machine, are commonly used to analyze spectral data. However, in this study, we employed the learning vector quantization (LVQ) neural network, which is typically used for pattern recognition. By applying the proposed method, a normal diagnosis accuracy of 85.7% and a glioma diagnosis accuracy of 89.5% were achieved. The LVQ neural network is a recent approach to excavating Raman spectra information. Moreover, it is fast and convenient, does not require the spectra peak counterpart, and achieves a relatively high accuracy. It can be used in brain tumor prognostics and in helping to optimize the cutting margins of gliomas.
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The First in Vivo Observation of 13C- 15N Coupling in Mammalian Brain
NASA Astrophysics Data System (ADS)
Kanamori, Keiko; Ross, Brian D.
2001-12-01
[5-13C,15N]Glutamine, with 1J(13C-15N) of 16 Hz, was observed in vivo in the brain of spontaneously breathing rats by 13C MRS at 4.7 T. The brain [5-13C]glutamine peak consisted of the doublet from [5-13C,15N]glutamine and the center [5-13C,14N]glutamine peak, resulting in an apparent triplet with a separation of 8 Hz. The time course of formation of brain [5-13C,15N]glutamine was monitored in vivo with a time resolution of 20-35 min. This [5-13C,15N]glutamine was formed by glial uptake of released neurotransmitter [5-13C]glutamate and its reaction with 15NH3 catalyzed by the glia-specific glutamine synthetase. The neurotransmitter glutamate C5 was selectively13C-enriched by intravenous [2,5-13C]glucose infusion to 13C-label whole-brain glutamate C5, followed by [12C]glucose infusion to chase 13C from the small and rapidly turning-over glial glutamate pool, leaving 13C mainly in the neurotransmitter [5-13C]glutamate pool, which is sequestered in vesicles until release. Hence, the observed [5-13C,15N]glutamine arises from a coupling between 13C of neuronal origin and 15N of glial origin. Measurement of the rate of brain [5-13C,15N]glutamine formation provides a novel noninvasive method of studying the kinetics of neurotransmitter uptake into glia in vivo, a process that is crucial for protecting the brain from glutamate excitotoxicity.
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Familiarity Affects Entrainment of EEG in Music Listening.
Kumagai, Yuiko; Arvaneh, Mahnaz; Tanaka, Toshihisa
2017-01-01
Music perception involves complex brain functions. The relationship between music and brain such as cortical entrainment to periodic tune, periodic beat, and music have been well investigated. It has also been reported that the cerebral cortex responded more strongly to the periodic rhythm of unfamiliar music than to that of familiar music. However, previous works mainly used simple and artificial auditory stimuli like pure tone or beep. It is still unclear how the brain response is influenced by the familiarity of music. To address this issue, we analyzed electroencelphalogram (EEG) to investigate the relationship between cortical response and familiarity of music using melodies produced by piano sounds as simple natural stimuli. The cross-correlation function averaged across trials, channels, and participants showed two pronounced peaks at time lags around 70 and 140 ms. At the two peaks the magnitude of the cross-correlation values were significantly larger when listening to unfamiliar and scrambled music compared to those when listening to familiar music. Our findings suggest that the response to unfamiliar music is stronger than that to familiar music. One potential application of our findings would be the discrimination of listeners' familiarity with music, which provides an important tool for assessment of brain activity.
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Cold-induced ependymin expression in zebrafish and carp brain: implications for cold acclimation.
Tang, S J; Sun, K H; Sun, G H; Lin, G; Lin, W W; Chuang, M J
1999-10-01
Cold acclimation has been suggested to be mediated by alternations in the gene expression pattern in the cold-adapted fish. To investigate the mechanism of cold acclimation in fish brain at the molecular level, relevant subsets of differentially expressed genes of interest were identified and cloned by the PCR-based subtraction suppression hybridization. Characterization of the selected cold-induced cDNA clones revealed one encoding ependymin. This gene was shown to be brain-specific. The expression of ependymin was induced by a temperature shift from 25 degrees C to 6 degrees C in Cyprinus carpio or 12 degrees C in Danio rerio. Activation of ependymin was detected 2 h after cold exposure and peaked at more than 10-fold at 12 h. This peak level remains unchanged until the temperature returns to 25 degrees C. Although the amount of soluble ependymin protein in brain was not changed by cold treatment, its level in the fibrous insoluble polymers increased 2-fold after exposure to low temperature. These findings indicate that the increase in ependymin expression is an early event that may play an important role in the cold acclimation of fish.
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Laser scattering by transcranial rat brain illumination
NASA Astrophysics Data System (ADS)
Sousa, Marcelo V. P.; Prates, Renato; Kato, Ilka T.; Sabino, Caetano P.; Suzuki, Luis C.; Ribeiro, Martha S.; Yoshimura, Elisabeth M.
2012-06-01
Due to the great number of applications of Low-Level-Laser-Therapy (LLLT) in Central Nervous System (CNS), the study of light penetration through skull and distribution in the brain becomes extremely important. The aim is to analyze the possibility of precise illumination of deep regions of the rat brain, measure the penetration and distribution of red (λ = 660 nm) and Near Infra-Red (NIR) (λ = 808 nm) diode laser light and compare optical properties of brain structures. The head of the animal (Rattus Novergicus) was epilated and divided by a sagittal cut, 2.3 mm away from mid plane. This section of rat's head was illuminated with red and NIR lasers in points above three anatomical structures: hippocampus, cerebellum and frontal cortex. A high resolution camera, perpendicularly positioned, was used to obtain images of the brain structures. Profiles of scattered intensities in the laser direction were obtained from the images. There is a peak in the scattered light profile corresponding to the skin layer. The bone layer gives rise to a valley in the profile indicating low scattering coefficient, or frontal scattering. Another peak in the region related to the brain is an indication of high scattering coefficient (μs) for this tissue. This work corroborates the use of transcranial LLLT in studies with rats which are subjected to models of CNS diseases. The outcomes of this study point to the possibility of transcranial LLLT in humans for a large number of diseases.
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Optimization of SSVEP brain responses with application to eight-command Brain-Computer Interface.
Bakardjian, Hovagim; Tanaka, Toshihisa; Cichocki, Andrzej
2010-01-18
This study pursues the optimization of the brain responses to small reversing patterns in a Steady-State Visual Evoked Potentials (SSVEP) paradigm, which could be used to maximize the efficiency of applications such as Brain-Computer Interfaces (BCI). We investigated the SSVEP frequency response for 32 frequencies (5-84 Hz), and the time dynamics of the brain response at 8, 14 and 28 Hz, to aid the definition of the optimal neurophysiological parameters and to outline the onset-delay and other limitations of SSVEP stimuli in applications such as our previously described four-command BCI system. Our results showed that the 5.6-15.3 Hz pattern reversal stimulation evoked the strongest responses, peaking at 12 Hz, and exhibiting weaker local maxima at 28 and 42 Hz. After stimulation onset, the long-term SSVEP response was highly non-stationary and the dynamics, including the first peak, was frequency-dependent. The evaluation of the performance of a frequency-optimized eight-command BCI system with dynamic neurofeedback showed a mean success rate of 98%, and a time delay of 3.4s. Robust BCI performance was achieved by all subjects even when using numerous small patterns clustered very close to each other and moving rapidly in 2D space. These results emphasize the need for SSVEP applications to optimize not only the analysis algorithms but also the stimuli in order to maximize the brain responses they rely on. (c) 2009 Elsevier Ireland Ltd. All rights reserved.
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Relationships between Electroencephalographic Spectral Peaks Across Frequency Bands
van Albada, S. J.; Robinson, P. A.
2013-01-01
The degree to which electroencephalographic spectral peaks are independent, and the relationships between their frequencies have been debated. A novel fitting method was used to determine peak parameters in the range 2–35 Hz from a large sample of eyes-closed spectra, and their interrelationships were investigated. Findings were compared with a mean-field model of thalamocortical activity, which predicts near-harmonic relationships between peaks. The subject set consisted of 1424 healthy subjects from the Brain Resource International Database. Peaks in the theta range occurred on average near half the alpha peak frequency, while peaks in the beta range tended to occur near twice and three times the alpha peak frequency on an individual-subject basis. Moreover, for the majority of subjects, alpha peak frequencies were significantly positively correlated with frequencies of peaks in the theta and low and high beta ranges. Such a harmonic progression agrees semiquantitatively with theoretical predictions from the mean-field model. These findings indicate a common or analogous source for different rhythms, and help to define appropriate individual frequency bands for peak identification. PMID:23483663
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Brain shape convergence in the adaptive radiation of New World monkeys
Aristide, Leandro; dos Reis, Sergio Furtado; Machado, Alessandra C.; Lima, Inaya; Lopes, Ricardo T.; Perez, S. Ivan
2016-01-01
Primates constitute one of the most diverse mammalian clades, and a notable feature of their diversification is the evolution of brain morphology. However, the evolutionary processes and ecological factors behind these changes are largely unknown. In this work, we investigate brain shape diversification of New World monkeys during their adaptive radiation in relation to different ecological dimensions. Our results reveal that brain diversification in this clade can be explained by invoking a model of adaptive peak shifts to unique and shared optima, defined by a multidimensional ecological niche hypothesis. Particularly, we show that the evolution of convergent brain phenotypes may be related to ecological factors associated with group size (e.g., social complexity). Together, our results highlight the complexity of brain evolution and the ecological significance of brain shape changes during the evolutionary diversification of a primate clade. PMID:26858427
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Apoptosis and gene expression in the developing mouse brain of fusarenon-X-treated pregnant mice.
Sutjarit, Samak; Nakayama, Shota M M; Ikenaka, Yoshinori; Ishizuka, Mayumi; Banlunara, Wijit; Rerkamnuaychoke, Worawut; Kumagai, Susumu; Poapolathep, Amnart
2014-08-17
Fusarenon-X (FX), a type B trichothecene mycotoxin, is mainly produced by Fusarium crookwellense, which occurs naturally in agricultural commodities, such as wheat and barley. FX has been shown to exert a variety of toxic effects on multiple targets in vitro. However, the embryonic toxicity of FX in vivo remains unclear. In the present study, we investigated FX-induced apoptosis and the relationship between the genetic regulatory mechanisms and FX-induced apoptosis in the developing mouse brain of FX-treated pregnant mice. Pregnant mice were orally administered FX (3.5 mg/kg b.w.) and were assessed at 0, 12, 24 and 48 h after treatment (HAT). Apoptosis in the fetal brain was determined using hematoxylin and eosin staining, the TUNEL method, immunohistochemistry for PCNA and electron microscopy. Gene expressions were evaluated using microarray and real time-reverse transcription polymerase chain reaction (qRT-PCR). Histopathological changes showed that the number of apoptotic cells in the telencephalon of the mouse fetus peaked at 12 HAT and decreased at 24 and 48 HAT. FX induced the up-regulation of Bax, Trp53 and Casp9 and down-regulated Bcl2 but the expression levels of Fas and Casp8 mRNA remained unchanged. These data suggested that FX induces apoptosis in the developing mouse brain in FX-treated dams. Moreover, the genetic regulatory mechanisms of FX-induced apoptosis are regulated by Bax, Bcl2, Trp53 and Casp9 or can be defined via an intrinsic apoptotic pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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Development of a rat model for studying blast-induced traumatic brain injury.
Cheng, Jingmin; Gu, Jianwen; Ma, Yuan; Yang, Tao; Kuang, Yongqin; Li, Bingcang; Kang, Jianyi
2010-07-15
Blast-induced traumatic brain injury (TBI) has been the predominant cause of neurotrauma in current military conflicts, and it is also emerging as a potential threat in civilian terrorism. The etiology of TBI, however, is poorly understood. Further study on the mechanisms and treatment of blast injury is urgently needed. We developed a unique rat model to simulate blast effects that commonly occur on the battlefield. An electric detonator with the equivalent of 400 mg TNT was developed as the explosive source. The detonator's peak overpressure and impulse of explosion shock determined the explosion intensity in a distance-dependent manner. Ninety-six male adult Sprague-Dawley rats were randomly divided into four groups: 5-cm, 7.5-cm, 10-cm, and control groups. The rat was fixed in a specially designed cabin with an adjustable aperture showing the frontal, parietal, and occipital parts of the head exposed to explosion; the eyes, ears, mouth, and nose were protected by the cabin. After each explosion, we assessed the physiologic, neuropathologic, and neurobehavioral consequences of blast injury. Changes of brain tissue water content and neuron-specific enolase (NSE) expression were detected. The results in the 7.5-cm group show that 87% rats developed apnea, limb seizure, poor appetite, and limpness. Diffuse subarachnoid hemorrhage and edema could be seen within the brain parenchyma, which showed a loss of integrity. Capillary damage and enlarged intercellular and vascular space in the cortex, along with a tattered nerve fiber were observed. These findings demonstrate that we have provided a reliable and reproducible blast-induced TBI model in rats. Copyright 2010 Elsevier B.V. All rights reserved.
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Soderstrom, Ken; Wilson, Ashley R
2013-11-01
Zebra finch song is a learned behavior dependent upon successful progress through a sensitive period of late-postnatal development. This learning is associated with maturation of distinct brain nuclei and the fiber tract interconnections between them. We have previously found remarkably distinct and dense CB1 cannabinoid receptor expression within many of these song control brain regions, implying a normal role for endocannabinoid signaling in vocal learning. Activation of CB1 receptors via daily treatments with exogenous agonist during sensorimotor stages of song learning (but not in adulthood) results in persistent alteration of song patterns. Now we are working to understand physiological changes responsible for this cannabinoid-altered vocal learning. We have found that song-altering developmental treatments are associated with changes in expression of endocannabinoid signaling elements, including CB1 receptors and the principal CNS endogenous agonist, 2-AG. Within CNS, 2-AG is produced largely through activity of the α isoform of the enzyme diacylglycerol lipase (DAGLα). To better appreciate the role of 2-AG production in normal vocal development we have determined the spatial distribution of DAGLα expression within zebra finch CNS during vocal development. Early during vocal development at 25 days, DAGLα staining is typically light and of fibroid processes. Staining peaks late in the sensorimotor stage of song learning at 75 days and is characterized by fiber, neuropil and some staining of both small and large cell somata. Results provide insight to the normal role for endocannabinoid signaling in the maturation of brain regions responsible for song learning and vocal-motor output, and suggest mechanisms by which exogenous cannabinoid exposure alters acquisition of this form of vocal communication. Copyright © 2013 Elsevier B.V. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Tan, P.; Dewey, S.L.; Gatley, S.J.
1994-05-01
The brain serotonin system is an important molecular target in drug development. SR 46349B is a propenone oxime ether derivative with a high affinity and selectivity for the serotonin 5HT2 receptor (Kd=1.2 nM). We have labeled SR 46349B with carbon-11 via N-methylation of a nor-precursor (supplied by Sanofi Recherche) with C-11 methyl iodide. Purification by HPLC gave [11C]SR 46349B in 98% radiochemical purity with a specific activity of 1.5 Ci/{mu}mol. Serial PET studies were carried out in a baboon for a 60 minute study period with a two hour time interval between studies. The first study was at baseline andmore » the second after pretreatment with altanserin (0.5 mg/kg iv, 30 min prior to [11C]SR 46349B). Carbon-11 peaked at ca. 20 minutes in the frontal, parietal, temporal and occipital cortices where it plateaued for the rest of the study. Cerebellum, thalamus and striatum peaked at ca. 10 minutes and cleared to 62%, 72% and 80% of peak by 60 min. At 60 minutes, the frontal cortex to cerebellum ratio was 1.5. Treatment with altanserin reduced the frontal cortex to cerebellum ratio to 1.0. HPLC of mouse brain homogenate after [11C]SR 46349B showed >94% of the C-11 was parent compound. Microdialysis in freely moving rats after injection of SR 46349B (n=6; 10 mg/kg, ip) showed an average peak increase in extracellular dopamine of 375% which is higher than the 150% effect of altanserin. Spontaneous movements were markedly reduced. The pharmacokinetics of [11C] SR 46349B in cortical areas is consistent with the long term effects of SR 46349B on 5HT2 receptors and the elevations in extracellular dopamine without increased locomotor activity are consistent with serotonin mediated disinhibition of striatal dopamine release via blockade of serotonin receptors.« less
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Is the C-terminal flanking peptide of rat cholecystokinin double sulphated?
Adrian, T E; Domin, J; Bacarese-Hamilton, A J; Bloom, S R
1986-02-03
A specific radioimmunoassay was developed to the predicted nine amino acid C-terminal flanking peptide of cholecystokinin (peptide serine serine, PSS). In aqueous extracts of rat brain, PSS was undetectable unless the extracts were first treated with arylsulphatase, which also resulted in desulphation of cholecystokinin. The reverse-phase HPLC analysis of partially desulphated extracts showed the presence of two peaks intermediate to the naturally occurring and the completely desulphated forms. It is therefore proposed that the CCK-flanking peptide PSS has both tyrosine residues sulphated.
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van Rooij, Daan; Anagnostou, Evdokia; Arango, Celso; Auzias, Guillaume; Behrmann, Marlene; Busatto, Geraldo F; Calderoni, Sara; Daly, Eileen; Deruelle, Christine; Di Martino, Adriana; Dinstein, Ilan; Duran, Fabio Luis Souza; Durston, Sarah; Ecker, Christine; Fair, Damien; Fedor, Jennifer; Fitzgerald, Jackie; Freitag, Christine M; Gallagher, Louise; Gori, Ilaria; Haar, Shlomi; Hoekstra, Liesbeth; Jahanshad, Neda; Jalbrzikowski, Maria; Janssen, Joost; Lerch, Jason; Luna, Beatriz; Martinho, Mauricio Moller; McGrath, Jane; Muratori, Filippo; Murphy, Clodagh M; Murphy, Declan G M; O'Hearn, Kirsten; Oranje, Bob; Parellada, Mara; Retico, Alessandra; Rosa, Pedro; Rubia, Katya; Shook, Devon; Taylor, Margot; Thompson, Paul M; Tosetti, Michela; Wallace, Gregory L; Zhou, Fengfeng; Buitelaar, Jan K
2018-04-01
Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.
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Rose, Jessica; Vassar, Rachel; Cahill-Rowley, Katelyn; Stecher Guzman, Ximena; Hintz, Susan R; Stevenson, David K; Barnea-Goraly, Naama
2014-01-01
Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age. Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ≤ 1500 g, gestational age (GA) ≤ 32 weeks), who were admitted to the Lucile Packard Children's Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010 to 2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin. Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67 mg/dL, p= .006) compared to those without. The number of signal abnormalities observed on structural MRI correlated to mean and peak CRP (rho = .316, p = .002; rho = .318, p= .002). The number of signal abnormalities observed on MRI correlated with thalamus MD (left: r= .382, p= .002; right: r= .400, p= .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the strongest associations with neonatal risk factors. Higher thalamus MD on the left and right, respectively, was associated with lower GA (r = -.322, p = .009; r= -.381, p= .002), lower mean albumin (r = -.276, p= .029; r= -.385, p= .002), and lower mean bilirubin (r = -.293, p= .020; r= -.337 p= .007). Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopmental impairment and inform neuroprotective treatment for VLBW preterm infants.
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Iznak, E V; Iznak, A F; Pankratova, E A; Zavadenko, N N; Guzilova, L S; Guzilova, Iu I
2010-01-01
To assess objectively a dynamics of brain functional state, EEG spectral power and peak latency of the P300 component of cognitive auditory evoked potentials have been analyzed in adolescents during the course of nootropic therapy of residual asthenic consequences of traumatic brain injury (ICD-10 F07.2). The study included 76 adolescents, aged 12-18 years, who have undergone severe closed head trauma with brain commotion 1/2--5 years ago. Patients have been divided into 3 groups treated during one month with cerebrolysin, piracetam or magne-B6, respectively. After the end of the nootropic therapy, 77% of patients treated with cerebrolysin as well as 50% of patients treated with piracetam and magne-B6 have demonstrated the positive dynamics of their brain functional state that manifested itself in the appearance of occipital EEG alpha rhythm or in the increase of its spectral power; in the normalization of alpha rhythm frequency; in the decrease in the spectral power of slow wave (theta and delta) EEG activity, in the amount (up to the disappearance) of paroxysmal EEG activity, in the EEG response to hyperventilation and in the shortening of the P300 peak latency. Such positive changes of neurophysiological parameters have been associated with the improvement of clinical conditions of patients and correlated significantly with the dynamics of psychometric scores of attention and memory.
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NASA Astrophysics Data System (ADS)
Fujiwara, Osamu; Miyamoto, Kayoko; Wang, Jianqing
Biological hazards due to radio-frequency (RF) waves result mainly from the temperature rise in tissue. It should be, therefore, clarified to what extent the RF waves of portable telephones increase the temperature-rise in human brain that includes the central part governing the body-temperature regulation function. In this paper, we calculated both the specific absorption rate (SAR) and the resultant temperature-rise for 900 MHz and 2 GHz portable telephones using the finite-difference time-domain (FDTD) method for three typical use positions, i.e., the vertical position, cheek position and tilt position. As a result, we found that there was an increase for median and 1% value of the cumulative distribution of temperature-rise in children’s brains for any use positions of the portable telephones compared to that in the adult’s brain, and also that the increasing trend in children’s brains for temperature-rise is identical to the temperature-rise trend in children’s hypothalamus. In addition, we found that the ten-gram averaged peak SAR among the adult and children heads had the same trend as that of the 0.1% value of the relatively cumulative distribution of temperature-rise, which shows that the ten-gram averaged peak SAR reflects only the localized temperature-rise in the brain surface.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Dimberg, Y.
1995-09-01
C57/B1 mice were exposed during pregnancy (gestation days 0--19) to a 20 kHz magnetic field (MF). The asymmetric sawtooth-waveform magnetic field in the exposed racks had a flux density of 15 {micro}T (peak to peak). After 19 days, the exposure was terminated, and the mice were housed individually under normal laboratory conditions. On postnatal day (PD) 1, PD21, and PD308, various neurochemical markers in the brains of the offspring were investigated and the brains weighed. No significant difference was found in the whole brain weight at PD1 or PD21 between exposed offspring and control animals. However, on PD308, a significantmore » decrease in weight of the whole brain was detected in exposed animals. No significant differences were found in the weight of cortex, hippocampus, septum, or cerebellum on nay of the sampling occasions, nor were any significant differences detected in protein-, DNA-level, nerve growth factor (NGF), acetylcholine esterase- (AChE), or 2{prime},3{prime}-cyclic nucleotide 3{prime}-phosphodiesterase- (CNP; marker for oligodendrocytes) activities on PD21 in cerebellum. Cortex showed a more complex pattern of response to MF: MF treatment resulted in a decrease in DNA level and increases in the activities of CNP, AChE, and NGF protein. On PD308, the amount of DNA was significantly reduced in MF-treated cerebellum and CNP activity was still enhanced in MF-treated cortex compared to controls. Most of the effect of MF treatment during the embryonic period were similar to those induced by ionizing radiation but much weaker. However, the duration of the exposure required to elucidate the response of different markers to MF seems to be greater and effects appear later during development compared to responses to ionizing radiation.« less
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Long-Term Monitoring of Brain Dopamine Metabolism In Vivo with Carbon Paste Electrodes
O'Neill, Robert D.
2005-01-01
This review focuses on the stability of voltammetric signals recorded over periods of months with carbon paste electrodes (CPEs) implanted in the brain. The key interaction underlying this stability is between the pasting oil and brain lipids that are capable of inhibiting the fouling caused by proteins. In brain regions receiving a significant dopaminergic input, a peak due to the methylated metabolites of dopamine, principally homovanillic acid (HVA), is clearly resolved using slow sweep voltammetry. Although a number of factors limit the time resolution for monitoring brain HVA concentration dynamics, the stability of CPEs allows investigations of long-term effects of drugs, as well as behavioral studies, not possible using other in-vivo monitoring techniques.
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NASA Astrophysics Data System (ADS)
Anderson, Vitas
2003-10-01
The aim of this study is to examine the scale and significance of differences in peak specific energy absorption rate (SAR) in the brains of children and adults exposed to radiofrequency emissions from mobile phones. Estimates were obtained by method of multipole analysis of a three layered (scalp/cranium/brain) spherical head exposed to a nearby 0.4lgr dipole at 900 MHz. A literature review of head parameters that influence SAR induction revealed strong indirect evidence based on total body water content that there are no substantive age-related changes in tissue conductivity after the first year of life. However, it was also found that the thickness of the ear, scalp and cranium do decrease on average with decreasing age, though individual variability within any age group is very high. The model analyses revealed that compared to an average adult, the peak brain 10 g averaged SAR in mean 4, 8, 12 and 16 year olds (yo) is increased by a factor of 1.31, 1.23, 1.15 and 1.07, respectively. However, contrary to the expectations of a recent prominent expert review, the UK Stewart Report, the relatively small scale of these increases does not warrant any special precautionary measures for child mobile phone users since: (a) SAR testing protocols as contained in the CENELEC (2001) standard provide an additional safety margin which ensures that allowable localized SAR limits are not exceeded in the brain; (b) the maximum worst case brain temperature rise (~0.13 to 0.14 °C for an average 4 yo) in child users of mobile phones is well within safe levels and normal physiological parameters; and (c) the range of age average increases in children is less than the expected range of variation seen within the adult population.
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Macrophagic and microglial responses after focal traumatic brain injury in the female rat
2014-01-01
Background After central nervous system injury, inflammatory macrophages (M1) predominate over anti-inflammatory macrophages (M2). The temporal profile of M1/M2 phenotypes in macrophages and microglia after traumatic brain injury (TBI) in rats is unknown. We subjected female rats to severe controlled cortical impact (CCI) and examined the postinjury M1/M2 time course in their brains. Methods The motor cortex (2.5 mm left laterally and 1.0 mm anteriorly from the bregma) of anesthetized female Wistar rats (ages 8 to 10 weeks; N = 72) underwent histologically moderate to severe CCI with a 5-mm impactor tip. Separate cohorts of rats had their brains dissociated into cells for flow cytometry, perfusion-fixed for immunohistochemistry (IHC) and ex vivo magnetic resonance imaging or flash-frozen for RNA and protein analysis. For each analytical method used, separate postinjury times were included for 24 hours; 3 or 5 days; or 1, 2, 4 or 8 weeks. Results By IHC, we found that the macrophagic and microglial responses peaked at 5 to 7 days post-TBI with characteristics of mixed populations of M1 and M2 phenotypes. Upon flow cytometry examination of immunological cells isolated from brain tissue, we observed that peak M2-associated staining occurred at 5 days post-TBI. Chemokine analysis by multiplex assay showed statistically significant increases in macrophage inflammatory protein 1α and keratinocyte chemoattractant/growth-related oncogene on the ipsilateral side within the first 24 hours after injury relative to controls and to the contralateral side. Quantitative RT-PCR analysis demonstrated expression of both M1- and M2-associated markers, which peaked at 5 days post-TBI. Conclusions The responses of macrophagic and microglial cells to histologically severe CCI in the female rat are maximal between days 3 and 7 postinjury. The response to injury is a mixture of M1 and M2 phenotypes. PMID:24761998
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Effect of growth hormone deficiency on brain structure, motor function and cognition.
Webb, Emma A; O'Reilly, Michelle A; Clayden, Jonathan D; Seunarine, Kiran K; Chong, Wui K; Dale, Naomi; Salt, Alison; Clark, Chris A; Dattani, Mehul T
2012-01-01
The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone <6.7 µg/l) and idiopathic short stature (peak growth hormone >10 µg/l) underwent cognitive assessment, diffusion tensor imaging and volumetric magnetic resonance imaging prior to commencing growth hormone treatment. Total brain, corpus callosal, hippocampal, thalamic and basal ganglia volumes were determined using Freesurfer. Fractional anisotropy (a marker of white matter structural integrity) images were aligned and tract-based spatial statistics performed. Fifteen children (mean 8.8 years of age) with isolated growth hormone deficiency [peak growth hormone <6.7 µg/l (mean 3.5 µg/l)] and 14 controls (mean 8.4 years of age) with idiopathic short stature [peak growth hormone >10 µg/l (mean 15 µg/l) and normal growth rate] were recruited. Compared with controls, children with isolated growth hormone deficiency had lower Full-Scale IQ (P < 0.01), Verbal Comprehension Index (P < 0.01), Processing Speed Index (P < 0.05) and Movement-Assessment Battery for Children (P < 0.008) scores. Verbal Comprehension Index scores correlated significantly with insulin-like growth factor-1 (P < 0.03) and insulin-like growth factor binding protein-3 (P < 0.02) standard deviation scores in isolated growth hormone deficiency. The splenium of the corpus callosum, left globus pallidum, thalamus and hippocampus (P < 0.01) were significantly smaller; and corticospinal tract (bilaterally; P < 0.045, P < 0.05) and corpus callosum (P < 0.05) fractional anisotropy were significantly lower in the isolated growth hormone deficiency group. Basal ganglia volumes and bilateral corticospinal tract fractional anisotropy correlated significantly with Movement-Assessment Battery for Children scores, and corpus callosum fractional anisotropy with Full-Scale IQ and Processing Speed Index. In patients with isolated growth hormone deficiency, white matter abnormalities in the corpus callosum and corticospinal tract, and reduced thalamic and globus pallidum volumes relate to deficits in cognitive function and motor performance. Follow-up studies that investigate the course of the structural and cognitive deficits on growth hormone treatment are now required to confirm that growth hormone deficiency impacts significantly on brain structure, cognitive function and motor performance.
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Spatiotemporal Neural Dynamics of Word Understanding in 12- to 18-Month-Old-Infants
Leonard, Matthew K.; Brown, Timothy T.; Hagler, Donald J.; Curran, Megan; Dale, Anders M.; Elman, Jeffrey L.; Halgren, Eric
2011-01-01
Learning words is central in human development. However, lacking clear evidence for how or where language is processed in the developing brain, it is unknown whether these processes are similar in infants and adults. Here, we use magnetoencephalography in combination with high-resolution structural magnetic resonance imaging to noninvasively estimate the spatiotemporal distribution of word-selective brain activity in 12- to 18-month-old infants. Infants watched pictures of common objects and listened to words that they understood. A subset of these infants also listened to familiar words compared with sensory control sounds. In both experiments, words evoked a characteristic event-related brain response peaking ∼400 ms after word onset, which localized to left frontotemporal cortices. In adults, this activity, termed the N400m, is associated with lexico-semantic encoding. Like adults, we find that the amplitude of the infant N400m is also modulated by semantic priming, being reduced to words preceded by a semantically related picture. These findings suggest that similar left frontotemporal areas are used for encoding lexico-semantic information throughout the life span, from the earliest stages of word learning. Furthermore, this ontogenetic consistency implies that the neurophysiological processes underlying the N400m may be important both for understanding already known words and for learning new words. PMID:21209121
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NASA Astrophysics Data System (ADS)
Pichiorri, F.; De Vico Fallani, F.; Cincotti, F.; Babiloni, F.; Molinari, M.; Kleih, S. C.; Neuper, C.; Kübler, A.; Mattia, D.
2011-04-01
The main purpose of electroencephalography (EEG)-based brain-computer interface (BCI) technology is to provide an alternative channel to support communication and control when motor pathways are interrupted. Despite the considerable amount of research focused on the improvement of EEG signal detection and translation into output commands, little is known about how learning to operate a BCI device may affect brain plasticity. This study investigated if and how sensorimotor rhythm-based BCI training would induce persistent functional changes in motor cortex, as assessed with transcranial magnetic stimulation (TMS) and high-density EEG. Motor imagery (MI)-based BCI training in naïve participants led to a significant increase in motor cortical excitability, as revealed by post-training TMS mapping of the hand muscle's cortical representation; peak amplitude and volume of the motor evoked potentials recorded from the opponens pollicis muscle were significantly higher only in those subjects who develop a MI strategy based on imagination of hand grasping to successfully control a computer cursor. Furthermore, analysis of the functional brain networks constructed using a connectivity matrix between scalp electrodes revealed a significant decrease in the global efficiency index for the higher-beta frequency range (22-29 Hz), indicating that the brain network changes its topology with practice of hand grasping MI. Our findings build the neurophysiological basis for the use of non-invasive BCI technology for monitoring and guidance of motor imagery-dependent brain plasticity and thus may render BCI a viable tool for post-stroke rehabilitation.
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Carbon dioxide field flooding reduces neurologic impairment after open heart surgery.
Martens, Sven; Neumann, Katrin; Sodemann, Christian; Deschka, Heinz; Wimmer-Greinecker, Gerhard; Moritz, Anton
2008-02-01
Air emboli released from incompletely deaired cardiac chambers may cause neurocognitive decline after open heart surgery. Carbon dioxide (CO2) field flooding is reported to reduce residual intracavital air during cardiac surgery. A protective effect of carbon dioxide insufflation on postoperative brain function remains unproven in clinical trials. Eighty patients undergoing heart valve operations by median sternotomy were randomly assigned to either CO2 insufflation (group I, n = 39) or unprotected controls (group II, n = 41). Preoperative evaluation included neurocognitive test batteries consisting of six different tests, and objective measurements of brain function by means of P300 wave auditory-evoked potentials (peak latencies, ms). Neurocognitive testing and P300 measurements were repeated on postoperative day 5. Neurocognitive deficit (ND) was defined as a 20% decrement in two or more tests. Preoperatively, P300 peak latencies did not differ between groups (374 +/- 75 vs 366 +/- 72 ms, not significant [n.s.]). Five days after surgery, P300 peak latencies were significantly shorter with CO2 protection as compared with the unprotected control group (group I: 390 +/- 68 ms, group II: 429 +/- 75 ms, p = 0.02). Clinical outcome was comparable as for mortality (group I: 1 patient; group II: 2 patients) and cerebrovascular events or confusional syndromes (group I: 5 patients; group II: 4 patients) or other clinical variables as intubation time or hospital stay. Neurocognitive test batteries did not reveal differences between groups. Shorter P300 peak latencies after surgery indicate less brain damage in patients who underwent heart valve operations with CO2 flooding of the thoracic cavity. Even if these findings were not supported by clinical results or neurocognitive test batteries in our cohort, carbon dioxide field flooding has proven efficiency and should be advocated for all patients undergoing open heart surgery.
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Mitsui, Tetsuo; Taniguchi, Naofumi; Kawasaki, Nobuchika; Kagami, Yoshihiro; Arita, Jun
2011-04-01
Fetal exposure to dioxins affects brain development and influences behaviors in human and laboratory animals. However, the cellular target and mechanisms of the neurotoxic action of dioxins are largely unknown. To investigate the molecular basis for the neurotoxicity of dioxins, pregnant C57BL/6 mice were exposed to 5 µg kg(-1) body weight of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by a single gavage on gestational day 12.5 (GD 12.5), and gene expression of the whole fetal brain at GD 18.5 was profiled by DNA microarray analysis. The analysis revealed that the expression of two chemokine genes, Cxcl4 and Cxcl7, was up-regulated by TCDD exposure. Real-time PCR analysis verified that they were up-regulated by TCDD in both male and female brains, while the mRNA levels of a majority of other chemokines and their receptor genes were not affected. The up-regulation was TCDD dose-dependent and peaked at GD 15.5-18.5. In situ hybridization analysis showed that the Cxcl4 mRNA expression was localized in part of the surface of cerebral cortex and that the level was increased by TCDD treatment. These results suggest that Cxcl4 and Cxcl7 play a role in the development of neurobehavioral alterations that are triggered by in utero TCDD exposure and later surface in adults. Copyright © 2011 John Wiley & Sons, Ltd.
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Functional connectivity analysis of brain hemodynamics during rubber hand illusion.
Arizono, Naoki; Kondo, Toshiyuki
2015-08-01
Embodied cognition has been eagerly studied in the recent neuroscience research field. In particular, hand ownership has been investigated through the rubber hand illusion (RHI). Most of the research measured the brain activities during the RHI by using EEG, fMRI, etc., however, near-infrared spectroscopy (NIRS) has not yet been utilized. Here we attempt to measure the brain activities during the RHI task with NIRS, and analyze the functional connectivity so as to understand the relationship between NIRS features and the state of embodied cognition. For the purpose, we developed a visuo-tactile stimulator in the study. As a result, we found that the subjects felt illusory experience showed significant peaks of oxy-Hb in both prefrontal and premotor cortices during RHI. Furthermore, we confirmed a reliable causality connection from right prefrontal to right premotor cortex. This result suggests that the RHI is associated with the neural circuits underlying motor control. Therefore, we considered that the RHI with the functional connectivity analysis will become an appropriate model investigating a biomarker for neurorehabilitation, and the diagnosis of the mental disorders.
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Murbach, Manuel; Christopoulou, Maria; Crespo-Valero, Pedro; Achermann, Peter; Kuster, Niels
2012-09-01
A novel exposure system for double-blind human electromagnetic provocation studies has been developed that satisfies the precision, control of fields and potential artifacts, and provides the flexibility to investigate the response of hypotheses-driven electromagnetic field exposure schemes on brain function, ranging from extremely low frequency (ELF) to radio frequency (RF) fields. The system can provide the same exposure of the lateral cerebral cortex at two different RF frequencies (900 and 2140 MHz) but with different exposure levels at subcortical structures, and also allows uniform ELF magnetic field exposure of the brain. The RF modulation and ELF signal are obtained by a freely programmable arbitrary signal generator allowing a wide range of worst-case exposure scenarios to be simulated, including those caused by wireless devices. The maximum achievable RF exposure is larger than 60 W/kg peak spatial specific absorption rate averaged over 10 g of tissue. The maximum ELF magnetic field exposure of the brain is 800 A/m at 50 Hz with a deviation from uniformity of 8% (SD). Copyright © 2012 Wiley Periodicals, Inc.
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Llinás, Rodolfo R.; Ustinin, Mikhail N.; Rykunov, Stanislav D.; Boyko, Anna I.; Sychev, Vyacheslav V.; Walton, Kerry D.; Rabello, Guilherme M.; Garcia, John
2015-01-01
A new method for the analysis and localization of brain activity has been developed, based on multichannel magnetic field recordings, over minutes, superimposed on the MRI of the individual. Here, a high resolution Fourier Transform is obtained over the entire recording period, leading to a detailed multi-frequency spectrum. Further analysis implements a total decomposition of the frequency components into functionally invariant entities, each having an invariant field pattern localizable in recording space. The method, addressed as functional tomography, makes it possible to find the distribution of magnetic field sources in space. Here, the method is applied to the analysis of simulated data, to oscillating signals activating a physical current dipoles phantom, and to recordings of spontaneous brain activity in 10 healthy adults. In the analysis of simulated data, 61 dipoles are localized with 0.7 mm precision. Concerning the physical phantom the method is able to localize three simultaneously activated current dipoles with 1 mm precision. Spatial resolution 3 mm was attained when localizing spontaneous alpha rhythm activity in 10 healthy adults, where the alpha peak was specified for each subject individually. Co-registration of the functional tomograms with each subject's head MRI localized alpha range activity to the occipital and/or posterior parietal brain region. This is the first application of this new functional tomography to human brain activity. The method successfully provides an overall view of brain electrical activity, a detailed spectral description and, combined with MRI, the localization of sources in anatomical brain space. PMID:26528119
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McMillan, Douglas M; Tyndale, Rachel F
2017-12-01
Repeated opioid administration produces analgesic tolerance, which may lead to dose escalation. Brain CYP2D metabolizes codeine to morphine, a bioactivation step required for codeine analgesia. Higher brain, but not liver, CYP2D is found in smokers and nicotine induces rat brain, but not liver, CYP2D expression and activity. Nicotine induction of rat brain CYP2D increases acute codeine conversion to morphine, and analgesia, however the role of brain CYP2D on the effects of repeated codeine exposure and tolerance is unknown. Rats were pretreated with nicotine (brain CYP2D inducer; 1mg/kg subcutaneously) or vehicle (saline; 1ml/kg subcutaneously). Codeine (40-60mg/kg oral-gavage) or morphine (20-30mg/kg oral-gavage) was administered daily and analgesia was assessed daily using the tail-flick reflex assay. Nicotine (versus saline) pretreatment increased acute codeine analgesia (1.32-fold change in AUC 0-60 min ; p<0.05) and the rate of loss of peak analgesia (11.42%/day versus 4.20%; p<0.006) across the first four days of codeine administration (time to negligible analgesia). Inducing brain CYP2D with nicotine did not alter acute morphine analgesia (1.03-fold; p>0.8), or the rate of morphine tolerance (8.1%/day versus 7.6%; p>0.9). The rate of both codeine and morphine tolerance (loss in peak analgesia from day 1 to day 4) correlated with initial analgesic response on day 1 (R=0.97, p<001). Increasing brain CYP2D altered initial analgesia and subsequent rate of tolerance. Variation in an individual's initial response to analgesic (e.g. high initial dose, smoking) may affect the rate of tolerance, and thereby the risk for dose escalation and/or opioid dependence. Copyright © 2017 Elsevier Inc. All rights reserved.
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Li, Ying; Korgaonkar, Akshata A; Swietek, Bogumila; Wang, Jianfeng; Elgammal, Fatima S; Elkabes, Stella; Santhakumar, Vijayalakshmi
2015-02-01
Concussive brain injury results in neuronal degeneration, microglial activation and enhanced excitability in the hippocampal dentate gyrus, increasing the risk for epilepsy and memory dysfunction. Endogenous molecules released during injury can activate innate immune responses including toll-like receptor 4 (TLR4). Recent studies indicate that immune mediators can modulate neuronal excitability. Since non-specific agents that reduce TLR4 signaling can limit post-traumatic neuropathology, we examined whether TLR4 signaling contributes to early changes in dentate excitability after brain injury. Concussive brain injury caused a transient increase in hippocampal TLR4 expression within 4h, which peaked at 24h. Post-injury increase in TLR4 expression in the dentate gyrus was primarily neuronal and persisted for one week. Acute, in vitro treatment with TLR4 ligands caused bidirectional modulation of dentate excitability in control and brain-injured rats, with a reversal in the direction of modulation after brain injury. TLR4 antagonists decreased, and agonist increased, afferent-evoked dentate excitability one week after brain injury. NMDA receptor antagonist did not occlude the ability of LPS-RS, a TLR4 antagonist, to decrease post-traumatic dentate excitability. LPS-RS failed to modulate granule cell NMDA EPSCs but decreased perforant path-evoked non-NMDA EPSC peak amplitude and charge transfer in both granule cells and mossy cells. Our findings indicate an active role for TLR4 signaling in early post-traumatic dentate hyperexcitability. The novel TLR4 modulation of non-NMDA glutamatergic currents, identified herein, could represent a general mechanism by which immune activation influences neuronal excitability in neurological disorders that recruit sterile inflammatory responses. Copyright © 2014 Elsevier Inc. All rights reserved.
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Cros, Maria; Geleijns, Jacob; Joemai, Raoul M S; Salvadó, Marçal
2016-01-01
The purpose of this study was to estimate the patient dose from perfusion CT examinations of the brain, lung tumors, and the liver on a cone-beam 320-MDCT scanner using a Monte Carlo simulation and the recommendations of the International Commission on Radiological Protection (ICRP). A Monte Carlo simulation based on the Electron Gamma Shower Version 4 package code was used to calculate organ doses and the effective dose in the reference computational phantoms for an adult man and adult woman as published by the ICRP. Three perfusion CT acquisition protocols--brain, lung tumor, and liver perfusion--were evaluated. Additionally, dose assessments were performed for the skin and for the eye lens. Conversion factors were obtained to estimate effective doses and organ doses from the volume CT dose index and dose-length product. The sex-averaged effective doses were approximately 4 mSv for perfusion CT of the brain and were between 23 and 26 mSv for the perfusion CT body protocols. The eye lens dose from the brain perfusion CT examination was approximately 153 mGy. The sex-averaged peak entrance skin dose (ESD) was 255 mGy for the brain perfusion CT studies, 157 mGy for the lung tumor perfusion CT studies, and 172 mGy for the liver perfusion CT studies. The perfusion CT protocols for imaging the brain, lung tumors, and the liver performed on a 320-MDCT scanner yielded patient doses that are safely below the threshold doses for deterministic effects. The eye lens dose, peak ESD, and effective doses can be estimated for other clinical perfusion CT examinations from the conversion factors that were derived in this study.
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Recovery function of the human brain stem auditory-evoked potential.
Kevanishvili, Z; Lagidze, Z
1979-01-01
Amplitude reduction and peak latency prolongation were observed in the human brain stem auditory-evoked potential (BEP) with preceding (conditioning) stimulation. At a conditioning interval (CI) of 5 ms the alteration of BEP was greater than at a CI of 10 ms. At a CI of 10 ms the amplitudes of some BEP components (e.g. waves I and II) were more decreased than those of others (e.g. wave V), while the peak latency prolongation did not show any obvious component selectivity. At a CI of 5 ms, the extent of the amplitude decrement of individual BEP components differed less, while the increase in the peak latencies of the later components was greater than that of the earlier components. The alterations of the parameters of the test BEPs at both CIs are ascribed to the desynchronization of intrinsic neural events. The differential amplitude reduction at a CI of 10 ms is explained by the different durations of neural firings determining various effects of desynchronization upon the amplitudes of individual BEP components. The decrease in the extent of the component selectivity and the preferential increase in the peak latencies of the later BEP components observed at a CI of 5 ms are explained by the intensification of the mechanism of the relative refractory period.
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Head, Elizabeth; Schmitt, Frederick A.; Davis, Paulina R.; Neltner, Janna H.; Jicha, Gregory A.; Abner, Erin L.; Smith, Charles D.; Van Eldik, Linda J.; Kryscio, Richard J.; Scheff, Stephen W.
2011-01-01
Human studies are reviewed concerning whether “aging”-related mechanisms contribute to Alzheimer’s disease (AD) pathogenesis. AD is defined by specific neuropathology: neuritic amyloid plaques and neocortical neurofibrillary tangles. AD pathology is driven by genetic factors related not to aging per se, but instead to the amyloid precursor protein (APP). In contrast to genes involved in APP-related mechanisms, there is no firm connection between genes implicated in human “accelerated aging” diseases (progerias) and AD. The epidemiology of AD in advanced age is highly relevant but deceptively challenging to address given the low autopsy rates in most countries. In extreme old age, brain diseases other than AD approximate AD prevalence while the impact of AD pathology appears to peak by age 95 and decline thereafter. Many distinct brain diseases other than AD afflict older human brains and contribute to cognitive impairment. Additional prevalent pathologies include cerebrovascular disease and hippocampal sclerosis, both high-morbidity brain diseases that appear to peak in incidence later than AD chronologically. Because of these common brain diseases of extreme old age, the epidemiology differs between clinical “dementia” and the subset of dementia cases with AD pathology. Additional aging-associated mechanisms for cognitive decline such as diabetes and synapse loss have been linked to AD and these hypotheses are discussed. Criteria are proposed to define an “aging-linked” disease, and AD fails all of these criteria. In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging. PMID:21516511
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Beet Root Juice: An Ergogenic Aid for Exercise and the Aging Brain.
Petrie, Meredith; Rejeski, W Jack; Basu, Swati; Laurienti, Paul J; Marsh, Anthony P; Norris, James L; Kim-Shapiro, Daniel B; Burdette, Jonathan H
2017-09-01
Exercise has positive neuroplastic effects on the aging brain. It has also been shown that ingestion of beet root juice (BRJ) increases blood flow to the brain and enhances exercise performance. Here, we examined whether there are synergistic effects of BRJ and exercise on neuroplasticity in the aging brain. Peak metabolic equivalent (MET) capacity and resting-state magnetic resonance imaging functional brain network organization are reported on 26 older (mean age = 65.4 years) participants randomly assigned to 6 weeks of exercise + BRJ or exercise + placebo. Somatomotor community structure consistency was significantly enhanced in the exercise + BRJ group following the intervention (MBRJ = -2.27, SE = 0.145, MPlacebo = -2.89, SE = 0.156, p = .007). Differences in second-order connections between the somatomotor cortex and insular cortex were also significant; the exercise + BRJ group (M = 3.28, SE = 0.167) had a significantly lower number of connections than exercise + placebo (M = 3.91, SE = 0.18, p = .017) following the intervention. Evaluation of peak MET capacity revealed a trend for the exercise + BRJ group to have higher MET capacity following the intervention. Older adults who exercised and consumed BRJ demonstrated greater consistency within the motor community and fewer secondary connections with the insular cortex compared with those who exercised without BRJ. The exercise + BRJ group had brain networks that more closely resembled those of younger adults, showing the potential enhanced neuroplasticity conferred by combining exercise and BRJ consumption. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Liang, M; Lee, M C; O'Neill, J; Dickenson, A H; Iannetti, G D
2016-08-01
Central sensitization (CS), the increased sensitivity of the central nervous system to somatosensory inputs, accounts for secondary hyperalgesia, a typical sign of several painful clinical conditions. Brain potentials elicited by mechanical punctate stimulation using flat-tip probes can provide neural correlates of CS, but their signal-to-noise ratio is limited by poor synchronization of the afferent nociceptive input. Additionally, mechanical punctate stimulation does not activate nociceptors exclusively. In contrast, low-intensity intraepidermal electrical stimulation (IES) allows selective activation of type II Aδ-mechano-heat nociceptors (II-AMHs) and elicits reproducible brain potentials. However, it is unclear whether hyperalgesia from IES occurs and coexists with secondary mechanical punctate hyperalgesia, and whether the magnitude of the electroencephalographic (EEG) responses evoked by IES within the hyperalgesic area is increased. To address these questions, we explored the modulation of the psychophysical and EEG responses to IES by intraepidermal injection of capsaicin in healthy human subjects. We obtained three main results. First, the intensity of the sensation elicited by IES was significantly increased in participants who developed robust mechanical punctate hyperalgesia after capsaicin injection (i.e., responders), indicating that hyperalgesia from IES coexists with punctate mechanical hyperalgesia. Second, the N2 peak magnitude of the EEG responses elicited by IES was significantly increased after the intraepidermal injection of capsaicin in responders only. Third, a receiver-operator characteristics analysis showed that the N2 peak amplitude is clearly predictive of the presence of CS. These findings suggest that the EEG responses elicited by IES reflect secondary hyperalgesia and therefore represent an objective correlate of CS. Copyright © 2016 the American Physiological Society.
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NASA Astrophysics Data System (ADS)
Chockanathan, Udaysankar; DSouza, Adora M.; Abidin, Anas Z.; Schifitto, Giovanni; Wismüller, Axel
2018-02-01
Resting-state functional MRI (rs-fMRI), coupled with advanced multivariate time-series analysis methods such as Granger causality, is a promising tool for the development of novel functional connectivity biomarkers of neurologic and psychiatric disease. Recently large-scale Granger causality (lsGC) has been proposed as an alternative to conventional Granger causality (cGC) that extends the scope of robust Granger causal analyses to high-dimensional systems such as the human brain. In this study, lsGC and cGC were comparatively evaluated on their ability to capture neurologic damage associated with HIV-associated neurocognitive disorders (HAND). Functional brain network models were constructed from rs-fMRI data collected from a cohort of HIV+ and HIV- subjects. Graph theoretic properties of the resulting networks were then used to train a support vector machine (SVM) model to predict clinically relevant parameters, such as HIV status and neuropsychometric (NP) scores. For the HIV+/- classification task, lsGC, which yielded a peak area under the receiver operating characteristic curve (AUC) of 0.83, significantly outperformed cGC, which yielded a peak AUC of 0.61, at all parameter settings tested. For the NP score regression task, lsGC, with a minimum mean squared error (MSE) of 0.75, significantly outperformed cGC, with a minimum MSE of 0.84 (p < 0.001, one-tailed paired t-test). These results show that, at optimal parameter settings, lsGC is better able to capture functional brain connectivity correlates of HAND than cGC. However, given the substantial variation in the performance of the two methods at different parameter settings, particularly for the regression task, improved parameter selection criteria are necessary and constitute an area for future research.
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Neonatal case of classic maple syrup urine disease: usefulness of (1) H-MRS in early diagnosis.
Sato, Takeshi; Muroya, Koji; Hanakawa, Junko; Asakura, Yumi; Aida, Noriko; Tomiyasu, Moyoko; Tajima, Go; Hasegawa, Tomonobu; Adachi, Masanori
2014-02-01
We describe a male neonate with classic maple syrup urine disease (MSUD) in metabolic crisis. On day 7 of life, he was referred to hospital because of coma and metabolic acidosis with maple syrup odor. On day 4 after admission, brain magnetic resonance imaging findings were consistent with encephalopathy due to MSUD. Proton magnetic resonance spectroscopy ((1) H-MRS) showed a large methyl resonance peak at 0.9 p.p.m. The diagnosis of MSUD was confirmed on low branched-chain α-keto acid dehydrogenase complex activity in lymphocyte. (1) H-MR spectra were obtained in 10 min, while it took at least several days to obtain the results of other diagnostic examinations. In convalescence, the peak at 0.9 p.p.m. decreased. The large methyl resonance peak at 0.9 p.p.m. in brain (1) H-MRS would be one of the earliest clues to the diagnosis of classic MSUD in the neonatal period, especially in metabolic crisis. © 2014 The Authors. Pediatrics International © 2014 Japan Pediatric Society.
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NASA Astrophysics Data System (ADS)
Raphael, Itay; Mahesula, Swetha; Purkar, Anjali; Black, David; Catala, Alexis; Gelfond, Jonathon A. L.; Forsthuber, Thomas G.; Haskins, William E.
2014-09-01
Central nervous system-specific proteins (CSPs), transported across the damaged blood-brain-barrier (BBB) to cerebrospinal fluid (CSF) and blood (serum), might be promising diagnostic, prognostic and predictive protein biomarkers of disease in individual multiple sclerosis (MS) patients because they are not expected to be present at appreciable levels in the circulation of healthy subjects. We hypothesized that microwave & magnetic (M2) proteomics of CSPs in brain tissue might be an effective means to prioritize putative CSP biomarkers for future immunoassays in serum. To test this hypothesis, we used M2 proteomics to longitudinally assess CSP expression in brain tissue from mice during experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Confirmation of central nervous system (CNS)-infiltrating inflammatory cell response and CSP expression in serum was achieved with cytokine ELISPOT and ELISA immunoassays, respectively, for selected CSPs. M2 proteomics (and ELISA) revealed characteristic CSP expression waves, including synapsin-1 and α-II-spectrin, which peaked at day 7 in brain tissue (and serum) and preceded clinical EAE symptoms that began at day 10 and peaked at day 20. Moreover, M2 proteomics supports the concept that relatively few CNS-infiltrating inflammatory cells can have a disproportionally large impact on CSP expression prior to clinical manifestation of EAE.
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Lemes, Marcos; Wang, Feiyue; Stern, Gary A; Ostertag, Sonja K; Chan, Hing Man
2011-12-01
Monitoring data have shown that the total monomethylmercury (CH(3) Hg(+) and its complexes; collectively referred as MeHg hereafter) concentrations in Arctic marine mammals have remained very high in recent decades. Toward a better understanding of the metabolic and toxicological implications of these high levels of MeHg, we report here on the molecular forms of MeHg in the muscle, brain, liver, and kidneys of 10 beluga whales from the western Canadian Arctic. In all tissues analyzed, monomethylmercury was found to be dominated by methylmercuric cysteinate, a specific form of MeHg believed to be able to transport across the blood-brain barrier. Another MeHg-thiol complex, methylmercuric glutathionate, was also detected in the muscle and, to a much lesser extent, in the liver and brain tissues. Furthermore, a profound inorganic Hg peak was detected in the liver and brain tissues, which showed the same retention time as a selenium (Se) peak, suggesting the presence of an Hg-Se complex, most likely an inorganic Hg complex with a selenoamino acid. These results provide the first analytical support that the binding of MeHg with glutathione and Se may have protected beluga whales from the toxic effect of high concentrations of MeHg in their body. Copyright © 2011 SETAC.
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In vivo bubble nucleation probability in sheep brain tissue.
Gateau, J; Aubry, J-F; Chauvet, D; Boch, A-L; Fink, M; Tanter, M
2011-11-21
Gas nuclei exist naturally in living bodies. Their activation initiates cavitation activity, and is possible using short ultrasonic excitations of high amplitude. However, little is known about the nuclei population in vivo, and therefore about the rarefaction pressure required to form bubbles in tissue. A novel method dedicated to in vivo investigations was used here that combines passive and active cavitation detection with a multi-element linear ultrasound probe (4-7 MHz). Experiments were performed in vivo on the brain of trepanated sheep. Bubble nucleation was induced using a focused single-element transducer (central frequency 660 kHz, f-number = 1) driven by a high power (up to 5 kW) electric burst of two cycles. Successive passive recording and ultrafast active imaging were shown to allow detection of a single nucleation event in brain tissue in vivo. Experiments carried out on eight sheep allowed statistical studies of the bubble nucleation process. The nucleation probability was evaluated as a function of the peak negative pressure. No nucleation event could be detected with a peak negative pressure weaker than -12.7 MPa, i.e. one order of magnitude higher than the recommendations based on the mechanical index. Below this threshold, bubble nucleation in vivo in brain tissues is a random phenomenon.
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Lépée-Lorgeoux, Isabelle; Betancur, Catalina; Souazé, Frédérique; Rostène, William; Bérod, Anne; Pélaprat, Didier
2000-01-01
The aim of the present study was to investigate the role of neurotensin in the regulation of NT1 receptors during postnatal development in the rat brain. Characterization of the ontogeny of neurotensin concentration and [125I]neurotensin binding to NT1 receptors in the brain at different embryonic and postnatal stages showed that neurotensin was highly expressed at birth, reaching peak levels at postnatal day 5 (P5), and decreasing thereafter. The transient rise in neurotensin levels preceded the maximal expression of NT1 receptors, observed at P10, suggesting that neurotensin may influence the developmental profile of NT1 receptors. Using primary cultures of cerebral cortex neurons from fetal rats, we showed that exposure to the neurotensin agonist JMV 449 (1 nM) decreased (−43%) the amount of NT1 receptor mRNA measured by reverse transcription-PCR, an effect that was abolished by the non-peptide NT1 receptor antagonist SR 48692 (1 μM). However, daily injection of SR 48692 to rat pups from birth for 5, 9 or 15 days, did not modify [125I]neurotensin binding in brain membrane homogenates. Moreover, postnatal blockade of neurotensin transmission did not alter the density and distribution of NT1 receptors assessed by quantitative autoradiography nor NT1 receptor mRNA expression measured by in situ hybridization in the cerebral cortex, caudate-putamen and midbrain. These results suggest that although NT1 receptor expression can be regulated in vitro by the agonist at an early developmental stage, neurotensin is not a major factor in the establishment of the ontogenetic pattern of these receptors in the rat brain. PMID:10797539
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Pike, Victor W.; Rash, Karen S.; Chen, Zhaogen; Pedregal, Concepción; Statnick, Michael A.; Kimura, Yasuyuki; Hong, Jinsoo; Zoghbi, Sami S.; Fujita, Masahiro; Toledo, Miguel A.; Diaz, Nuria; Gackenheimer, Susan L.; Tauscher, Johannes T.; Barth, Vanessa N.; Innis, Robert B.
2011-01-01
Positron emission tomography (PET) coupled to an effective radioligand could provide an important tool for understanding possible links between neuropsychiatric disorders and brain NOP (nociceptin/orphanin FQ peptide) receptors. We sought to develop such a PET radioligand. High-affinity NOP ligands were synthesized based on a 3-(2'-fluoro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-yl)-2(2-halobenzyl)-N-alkylpropanamide scaffold and from experimental screens in rats, with ex vivo LC-MS/MS measures, three ligands were identified for labeling with carbon-11 and evaluation with PET in monkey. Each ligand was labeled by 11C-methylation of an N-desmethyl precursor and studied in monkey under baseline and NOP receptor-preblock conditions. The three radioligands, [11C](S)-10a–c, gave similar results. Baseline scans showed high entry of radioactivity into brain to give a distribution reflecting that expected for NOP receptors. Pre-block experiments showed high early peak levels of brain radioactivity which rapidly declined to a much lower level than seen in baseline scans, thereby indicating a high level of receptor-specific binding in baseline experiments. Overall, [11C](S)-10c showed the most favorable receptor-specific signal and kinetics and is now selected for evaluation in human subjects. PMID:21438532
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The developing human brain: age-related changes in cortical, subcortical, and cerebellar anatomy.
Sussman, Dafna; Leung, Rachel C; Chakravarty, M Mallar; Lerch, Jason P; Taylor, Margot J
2016-04-01
This study is the first to characterize normal development and sex differences across neuroanatomical structures in cortical, subcortical, and cerebellar brain regions in a single large cohort. One hundred and ninety-two magnetic resonance images were examined from 96 typically developing females and 96 age-matched typically developing males from 4 to 18 years of age. Image segmentation of the cortex was conducted with CIVET, while that of the cerebellum, hippocampi, thalamus, and basal ganglia were conducted using the MAGeT algorithm. Cortical thickness analysis revealed that most cortical regions decrease linearly, while surface area increases linearly with age. Volume relative to total cerebrum followed a quadratic trend with age, with only the left supramarginal gyrus showing sexual dimorphism. Hippocampal relative volume increased linearly, while the thalamus, caudate, and putamen decreased linearly, and the cerebellum did not change with age. The relative volumes of several subcortical subregions followed inverted U-shaped trends that peaked at ~12 years of age. Many subcortical structures were found to be larger in females than in males, independently of age, while others showed a sex-by-age interaction. This study provides a comprehensive assessment of cortical, subcortical, and cerebellar growth patterns during normal development, and draws attention to the role of sex on neuroanatomical maturation throughout childhood and adolescence.
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Hansen, Kirk; Dau, Nathan; Feist, Florian; Deck, Caroline; Willinger, Rémy; Madey, Steven M.; Bottlang, Michael
2013-01-01
Angular acceleration of the head is a known cause of traumatic brain injury (TBI), but contemporary bicycle helmets lack dedicated mechanisms to mitigate angular acceleration. A novel Angular Impact Mitigation (AIM) system for bicycle helmets has been developed that employs an elastically suspended aluminum honeycomb liner to absorb linear acceleration in normal impacts as well as angular acceleration in oblique impacts. This study tested bicycle helmets with and without AIM technology to comparatively assess impact mitigation. Normal impact tests were performed to measure linear head acceleration. Oblique impact tests were performed to measure angular head acceleration and neck loading. Furthermore, acceleration histories of oblique impacts were analyzed in a computational head model to predict the resulting risk of TBI in the form of concussion and diffuse axonal injury (DAI). Compared to standard helmets, AIM helmets resulted in a 14% reduction in peak linear acceleration (p < 0.001), a 34% reduction in peak angular acceleration (p < 0.001), and a 22% to 32% reduction in neck loading (p < 0.001). Computational results predicted that AIM helmets reduced the risk of concussion and DAI by 27% and 44%, respectively. In conclusion, these results demonstrated that AIM technology could effectively improve impact mitigation compared to a contemporary expanded polystyrene-based bicycle helmet, and may enhance prevention of bicycle-related TBI. Further research is required. PMID:23770518
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ERIC Educational Resources Information Center
Gerlich, R. Nicholas; Browning, Leigh; Westermann, Lori
2010-01-01
Neuropsychologists have demonstrated the effect music has on the human brain, and that a peak "musical memory age" occurs around 14, when normal bodily maturation is in progress. A group of 114 college students between the ages of 19 and 25 was exposed to short clips of the top 20 songs from each of the 11 years during their youth;…
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Imaging separation of neuronal from vascular effects of cocaine on rat cortical brain in vivo
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yuan, Z.; Du, C.; Yuan, Z.
MRI techniques to study brain function assume coupling between neuronal activity, metabolism and flow. However, recent evidence of physiological uncoupling between neuronal and cerebrovascular events highlights the need for methods to simultaneously measure these three properties. We report a multimodality optical approach that integrates dual-wavelength laser speckle imaging (measures changes in blood flow, blood volume and hemoglobin oxygenation), digital-frequency-ramping optical coherence tomography (images quantitative 3D vascular network) and Rhod2 fluorescence (images intracellular calcium for measure of neuronal activity) at high spatiotemporal resolutions (30 {micro}m, 10 Hz) and over a large field of view (3 x 5 mm{sup 2}). We applymore » it to assess cocaine's effects in rat cortical brain and show an immediate decrease 3.5 {+-} 0.9 min, phase (1) in the oxygen content of hemoglobin and the cerebral blood flow followed by an overshoot 7.1 {+-} 0.2 min, phase (2) lasting over 20 min whereas Ca{sup 2+} increased immediately (peaked at t = 4.1 {+-} 0.4 min) and remained elevated. This enabled us to identify a delay (2.9 {+-} 0.5 min) between peak neuronal and vascular responses in phase 2. The ability of this multimodality optical approach for simultaneous imaging at high spatiotemporal resolutions permits us to distinguish the vascular versus cellular changes of the brain, thus complimenting other neuroimaging modalities for brain functional studies (e. g., PET, fMRI).« less
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Blast overpressure in rats: recreating a battlefield injury in the laboratory.
Long, Joseph B; Bentley, Timothy L; Wessner, Keith A; Cerone, Carolyn; Sweeney, Sheena; Bauman, Richard A
2009-06-01
Blast injury to the brain is the predominant cause of neurotrauma in current military conflicts, and its etiology is largely undefined. Using a compression-driven shock tube to simulate blast effects, we assessed the physiological, neuropathological, and neurobehavioral consequences of airblast exposure, and also evaluated the effect of a Kevlar protective vest on acute mortality in rats and on the occurrence of traumatic brain injury (TBI) in those that survived. This approach provides survivable blast conditions under which TBI can be studied. Striking neuropathological changes were caused by both 126- and 147-kPa airblast exposures. The Kevlar vest, which encased the thorax and part of the abdomen, greatly reduced airblast mortality, and also ameliorated the widespread fiber degeneration that was prominent in brains of rats not protected by a vest during exposure to a 126-kPa airblast. This finding points to a significant contribution of the systemic effects of airblast to its brain injury pathophysiology. Airblast of this intensity also disrupted neurologic and neurobehavioral performance (e.g., beam walking and spatial navigation acquisition in the Morris water maze). When immediately followed by hemorrhagic hypotension, with MAP maintained at 30 mm Hg, airblast disrupted cardiocompensatory resilience, as reflected by reduced peak shed blood volume, time to peak shed blood volume, and time to death. These findings demonstrate that shock tube-generated airblast can cause TBI in rats, in part through systemic mediation, and that the resulting brain injury significantly impacts acute cardiovascular homeostatic mechanisms as well as neurobehavioral function.
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Human brain cancer studied by resonance Raman spectroscopy
NASA Astrophysics Data System (ADS)
Zhou, Yan; Liu, Cheng-Hui; Sun, Yi; Pu, Yang; Boydston-White, Susie; Liu, Yulong; Alfano, Robert R.
2012-11-01
The resonance Raman (RR) spectra of six types of human brain tissues are examined using a confocal micro-Raman system with 532-nm excitation in vitro. Forty-three RR spectra from seven subjects are investigated. The spectral peaks from malignant meningioma, stage III (cancer), benign meningioma (benign), normal meningeal tissues (normal), glioblastoma multiforme grade IV (cancer), acoustic neuroma (benign), and pituitary adenoma (benign) are analyzed. Using a 532-nm excitation, the resonance-enhanced peak at 1548 cm-1 (amide II) is observed in all of the tissue specimens, but is not observed in the spectra collected using the nonresonance Raman system. An increase in the intensity ratio of 1587 to 1605 cm-1 is observed in the RR spectra collected from meningeal cancer tissue as compared with the spectra collected from the benign and normal meningeal tissue. The peak around 1732 cm-1 attributed to fatty acids (lipids) are diminished in the spectra collected from the meningeal cancer tumors as compared with the spectra from normal and benign tissues. The characteristic band of spectral peaks observed between 2800 and 3100 cm-1 are attributed to the vibrations of methyl (-CH3) and methylene (-CH2-) groups. The ratio of the intensities of the spectral peaks of 2935 to 2880 cm-1 from the meningeal cancer tissues is found to be lower in comparison with that of the spectral peaks from normal, and benign tissues, which may be used as a distinct marker for distinguishing cancerous tissues from normal meningeal tissues. The statistical methods of principal component analysis and the support vector machine are used to analyze the RR spectral data collected from meningeal tissues, yielding a diagnostic sensitivity of 90.9% and specificity of 100% when two principal components are used.
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Gomes, Joao A; Selim, Magdy; Cotleur, Anne; Hussain, M Shazam; Toth, Gabor; Koffman, Lauren; Asi, Khaled; Provencio, J Javier
2014-10-01
Iron-mediated oxidative damage has been implicated in the genesis of cerebral vasospasm in animal models of SAH. We sought to explore the relationship between levels of non-protein bound iron in cerebrospinal fluid and the development of brain injury in patients with aneurysmal SAH. Patients admitted with aneurysmal subarachnoid hemorrhage to a Neurointensive care unit of an academic, tertiary medical center, with Hunt and Hess grades 2-4 requiring ventriculostomy insertion as part of their clinical management were included in this pilot study. Samples of cerebrospinal fluid (CSF) were obtained on days 1, 3, and 5. A fluorometric assay that relies on an oxidation sensitive probe was used to measure unbound iron, and levels of iron-handling proteins were measured by means of enzyme-linked immunosorbent assays. We prospectively collected and recorded demographic, clinical, and radiological data. A total of 12 patients were included in this analysis. Median Hunt and Hess score on admission was 3.5 (IQR: 1) and median modified Fisher scale score was 4 (IQR: 1). Seven of 12 patients (58 %) developed delayed cerebral ischemia (DCI). Day 5 non-transferrin bound iron (NTBI) (7.88 ± 1 vs. 3.58 ± 0.8, p = 0.02) and mean NTBI (7.39 ± 0.4 vs. 3.34 + 0.4 p = 0.03) were significantly higher in patients who developed DCI. Mean redox-active iron, as well as day 3 levels of redox-active iron correlated with development of angiographic vasospasm in logistic regression analysis (p = 0.02); while mean redox-active iron and lower levels of ceruloplasmin on days 3, 5, and peak concentration were correlated with development of deep cerebral infarcts. Our preliminary data indicate a causal relationship between unbound iron and brain injury following SAH and suggest a possible protective role for ceruloplasmin in this setting, particularly in the prevention of cerebral ischemia. Further studies are needed to validate these findings and to probe their clinical significance.
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Chu, Jeffrey J; Beckwith, Jonathan G; Leonard, Daniel S; Paye, Corey M; Greenwald, Richard M
2012-01-01
It is estimated that 10-20% of United States soldiers returning from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) have suffered at least one instance of blast-induced traumatic brain injury (bTBI) with many reporting persistent symptomology and long-term effects. This variation in blast response may be related to the complexity of blast waves and the many mechanisms of injury, including over-pressurization due to the shock wave and potential for blunt impacts to the head from shrapnel or from other indirect impacts (e.g., building, ground, and vehicle). To help differentiate the effects of primary, secondary, and tertiary effects of blast, a custom sensor was developed to simultaneously measure over-pressurization and blunt impact. Moreover, a custom, complementary filter was designed to differentiate the measurements of blunt (low-frequency bandwidth) from over-pressurization (high-frequency bandwidth). The custom sensor was evaluated in the laboratory using a shock tube to simulate shock waves and a drop fixture to simulate head impacts. Both bare sensors and sensor embedded within an ACH helmet coupon were compared to laboratory reference transducers under multiple loading conditions (n = 5) and trials at each condition (n = 3). For all comparative measures, peak magnitude, peak impulse, and cross-correlation measures, R (2) values, were greater than 0.900 indicating excellent agreement of peak measurements and time-series comparisons with laboratory measures.
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Annotation and Structural Analysis of Sialylated Human Milk Oligosaccharides
Wu, Shuai; Grimm, Rudolf; German, J. Bruce; Lebrilla, Carlito B.
2011-01-01
Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. Sialic acids are typically found on the nonreducing end and are known binding sites for pathogens and aid in neonates’ brain development. Due to their negative charge and hydrophilic nature, they also help modulate cell-cell interactions. It has also been shown that sialic acids are involved in regulating the immune response and aid in brain development. In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. The precursor ions were further examined with collision-induced dissociation (CID). By applying the proper collision energy, isomers can be readily differentiated by diagnostic peaks and characteristic fragmentation patterns. A set of 30 SHMO structures with retention times, accurate masses and MS/MS spectra was deduced and incorporated into an HMO library. When combined with previously determined neutral components, a library with over 70 structures is obtained allowing high-throughput oligosaccharide structure identification. PMID:21133381
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Evans, M L; Hopkins, D; Macdonald, I A; Amiel, S A
2004-05-01
To investigate the potential for the non-glucose metabolic substrate alanine to support brain function during glucose deprivation in man. Seven healthy men were studied on two occasions using a hyperinsulinaemic glucose clamp to lower arterialized plasma glucose to 2.5 mmol/l, in the presence of either 2 mmol/kg/h alanine infusion or saline, measuring counter-regulatory hormonal responses, symptoms generated and cognitive function with a mini-battery of tests sensitive to hypoglycaemia. Alanine infusion elevated plasma alanine (peak value 1481 +/- 1260 vs. 138 +/- 32 micro mol/l, P = 0.02 alanine vs. saline) and lactate (peak value 3.09 +/- 0.14 vs. 2.05 +/- 0.12 mmol/l, P = 0.02). Cognitive function assessed by the Stroop word and colour subtests deteriorated less with alanine than saline (P < 0.01 for both). Other cognitive function tests deteriorated equally and counter-regulatory hormones rose equally during hypoglycaemia in both studies (P > 0.34) except for increased glucagon with alanine (peak 260 +/- 53 vs. 91 + 8 ng/l, P = 0.03). There was no significant effect of alanine on either autonomic or neuroglycopenic symptom scores. Some, but not all, aspects of cognitive performance may be supported by an alanine infusion during hypoglycaemia. It is not clear whether alanine supports brain function directly or via increased availability of lactate. These data contribute to the growing evidence that regional metabolic differences exist in the brain's ability to use non-glucose fuels during hypoglycaemia.
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Medical diagnosis imaging systems: image and signal processing applications aided by fuzzy logic
NASA Astrophysics Data System (ADS)
Hata, Yutaka
2010-04-01
First, we describe an automated procedure for segmenting an MR image of a human brain based on fuzzy logic for diagnosing Alzheimer's disease. The intensity thresholds for segmenting the whole brain of a subject are automatically determined by finding the peaks of the intensity histogram. After these thresholds are evaluated in a region growing, the whole brain can be identified. Next, we describe a procedure for decomposing the obtained whole brain into the left and right cerebral hemispheres, the cerebellum and the brain stem. Our method then identified the whole brain, the left cerebral hemisphere, the right cerebral hemisphere, the cerebellum and the brain stem. Secondly, we describe a transskull sonography system that can visualize the shape of the skull and brain surface from any point to examine skull fracture and some brain diseases. We employ fuzzy signal processing to determine the skull and brain surface. The phantom model, the animal model with soft tissue, the animal model with brain tissue, and a human subjects' forehead is applied in our system. The all shapes of the skin surface, skull surface, skull bottom, and brain tissue surface are successfully determined.
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Biomedical terahertz imaging with a quantum cascade laser
NASA Astrophysics Data System (ADS)
Kim, Seongsin M.; Hatami, Fariba; Harris, James S.; Kurian, Allison W.; Ford, James; King, Douglas; Scalari, Giacomo; Giovannini, Marcella; Hoyler, Nicolas; Faist, Jerome; Harris, Geoff
2006-04-01
We present biomedical imaging using a single frequency terahertz imaging system based on a low threshold quantum cascade laser emitting at 3.7THz (λ=81μm). With a peak output power of 4mW, coherent terahertz radiation and detection provide a relatively large dynamic range and high spatial resolution. We study image contrast based on water/fat content ratios in different tissues. Terahertz transmission imaging demonstrates a distinct anatomy in a rat brain slice. We also demonstrate malignant tissue contrast in an image of a mouse liver with developed tumors, indicating potential use of terahertz imaging for probing cancerous tissues.
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Pawlosky, Robert J; Kashiwaya, Yoshihiro; Srivastava, Shireesh; King, Michael T; Crutchfield, Calvin; Volkow, Nora; Kunos, George; Li, Ting-Kai; Veech, Richard L
2010-02-01
Previous studies in humans have shown that alcohol consumption decreased the rate of brain glucose utilization. We investigated whether the major metabolite of ethanol, acetate, could account for this observation by providing an alternate to glucose as an energy substrate for brain and the metabolic consequences of that shift. Rats were infused with solutions of sodium acetate, ethanol, or saline containing (13)C-2-glucose as a tracer elevating the blood ethanol (BEC) and blood acetate (BAcC) concentrations. After an hour, blood was sampled and the brains of animals were removed by freeze blowing. Tissue samples were analyzed for the intermediates of glucose metabolism, Krebs' cycle, acyl-coenzyme A (CoA) compounds, and amino acids. Mean peak BEC and BAcC were approximately 25 and 0.8 mM, respectively, in ethanol-infused animals. Peak blood BAcC increased to 12 mM in acetate-infused animals. Both ethanol and acetate infused animals had a lower uptake of (13)C-glucose into the brain compared to controls and the concentration of brain (13)C-glucose-6-phosphate varied inversely with the BAcC. There were higher concentrations of brain malonyl-CoA and somewhat lower levels of free Mg(2+) in ethanol-treated animals compared to saline controls. In acetate-infused animals the concentrations of brain lactate, alpha-ketoglutarate, and fumarate were higher. Moreover, the free cytosolic [NAD(+)]/[NADH] was lower, the free mitochondrial [NAD(+)]/[NADH] and [CoQ]/[CoQH(2)] were oxidized and the DeltaG' of ATP lowered by acetate infusion from -61.4 kJ to -59.9 kJ/mol. Animals with elevated levels of blood ethanol or acetate had decreased (13)C-glucose uptake into the brain. In acetate-infused animals elevated BAcC were associated with a decrease in (13)C-glucose phosphorylation. The co-ordinate decrease in free cytosolic NAD, oxidation of mitochondrial NAD and Q couples and the decrease in DeltaG' of ATP was similar to administration of uncoupling agents indicating that the metabolism of acetate in brain caused the mitochondrial voltage dependent pore to form.
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Pawlosky, Robert J.; Kashiwaya, Yoshihiro; Srivastava, Shireesh; King, Michael T.; Crutchfield, Calvin; Volkow, Nora; Kunos, George; Li, Ting-Kai; Veech, Richard L.
2010-01-01
Background Previous studies in humans have shown that alcohol consumption decreased the rate of brain glucose utilization. We investigated whether the major metabolite of ethanol, acetate, could account for this observation by providing an alternate to glucose as an energy substrate for brain and the metabolic consequences of that shift. Methods Rats were infused with solutions of sodium acetate, ethanol, or saline containing 13C-2-glucose as a tracer elevating the blood ethanol (BEC) and blood acetate (BAcC) concentrations. After an hour, blood was sampled and the brains of animals were removed by freeze blowing. Tissue samples were analyzed for the intermediates of glucose metabolism, Krebs’ cycle, acyl-coenzyme A (CoA) compounds, and amino acids. Results Mean peak BEC and BAcC were approximately 25 and 0.8 mM, respectively, in ethanol-infused animals. Peak blood BAcC increased to 12 mM in acetate-infused animals. Both ethanol and acetate infused animals had a lower uptake of 13C-glucose into the brain compared to controls and the concentration of brain 13C-glucose-6-phosphate varied inversely with the BAcC. There were higher concentrations of brain malonyl-CoA and somewhat lower levels of free Mg2+ in ethanol-treated animals compared to saline controls. In acetate-infused animals the concentrations of brain lactate, α-ketoglutarate, and fumarate were higher. Moreover, the free cytosolic [NAD+]/[NADH] was lower, the free mitochondrial [NAD+]/[NADH] and [CoQ]/[CoQH2] were oxidized and the ΔG′ of ATP lowered by acetate infusion from −61.4 kJ to −59.9 kJ/mol. Conclusions Animals with elevated levels of blood ethanol or acetate had decreased 13C-glucose uptake into the brain. In acetate-infused animals elevated BAcC were associated with a decrease in 13C-glucose phosphorylation. The co-ordinate decrease in free cytosolic NAD, oxidation of mitochondrial NAD and Q couples and the decrease in ΔG′ of ATP was similar to administration of uncoupling agents indicating that the metabolism of acetate in brain caused the mitochondrial voltage dependent pore to form. PMID:19951290
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Near-infrared signals associated with electrical stimulation of peripheral nerves
NASA Astrophysics Data System (ADS)
Fantini, Sergio; Chen, Debbie K.; Martin, Jeffrey M.; Sassaroli, Angelo; Bergethon, Peter R.
2009-02-01
We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms).
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Raman spectroscopy for diagnosis of glioblastoma multiforme
NASA Astrophysics Data System (ADS)
Clary, Candace Elise
Glioblastoma multiforme (GBM), the most common and most fatal malignant brain tumor, is highly infiltrative and incurable. Although improved prognosis has been demonstrated by surgically resecting the bulk tumor, a lack of clear borders at the tumor margins complicates the selection decision during surgery. This dissertation investigates the potential of Raman spectroscopy for distinguishing between normal and malignant brain tissue and sets the groundwork for a surgical diagnostic guide for resection of gross malignant gliomas. These studies revealed that Raman spectroscopy was capable of discriminating between normal scid mouse brain tissue and human xenograft tumors induced in those mice. The spectra of normal and malignant tissue were normalized by dividing by the respective magnitudes of the peaks near 1440 cm -1. Spectral differences include the shape of the broad peaks near 1440 cm-1 and 1660 cm-1 and the relative magnitudes of the peaks at 1264 cm-1, 1287 cm-1, 1297 cm-1, 1556 cm -1, 1586 cm-1, 1614 cm-1, and 1683 cm-1. From these studies emerged questions regarding how to objectively normalize and compare spectra for future automation. Some differences in the Raman spectra were shown to be inherent in the disease states of the cells themselves via differences in the Raman spectra of normal human astrocytes in culture and cultured cells derived from GBM tumors. The spectra of astrocytes and glioma cells were normalized by dividing by the respective magnitudes of the peaks near 1450 cm-1. The differences between the Raman spectra of normal and transformed cells include the ratio of the 1450 cm-1/1650 cm-1 peaks and the relative magnitudes of the peaks at 1181 cm-1, 1191 cm-1, 1225 cm-1, 1263 cm -1, 1300 cm-1, 1336 cm-1, 1477 cm-1, 1494 cm-1, and 1695 cm -1. Previous Raman spectroscopic studies of biological cells have shown that the magnitude of the Raman signal decreases over time, indicating sample damage. Cells exposed to laser excitation at similar power densities were evaluated in terms of mitochondrial oxidative/reductive activity as well as protein, RNA, and DNA syntheses. Although cell death was not significant, the cells' abilities to synthesize DNA, RNA, and protein were profoundly affected by the laser irradiation.
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Samoilov, Mikhail; Churilova, Anna; Gluschenko, Tatjana; Vetrovoy, Oleg; Dyuzhikova, Natalia; Rybnikova, Elena
2016-03-01
Acetylation of nucleosome histones results in relaxation of DNA and its availability for the transcriptional regulators, and is generally associated with the enhancement of gene expression. Although it is well known that activation of a variety of pro-adaptive genes represents a key event in the development of brain hypoxic/ischemic tolerance, the role of epigenetic mechanisms, in particular histone acetylation, in this process is still unexplored. The aim of the present study was to investigate changes in acetylation of histones in vulnerable brain neurons using original well-standardized model of hypobaric hypoxia and preconditioning-induced tolerance of the brain. Using quantitative immunohistochemistry and Western blot, effects of severe injurious hypobaric hypoxia (SH, 180mm Hg, 3h) and neuroprotective preconditioning mode (three episodes of 360mm Hg for 2h spaced at 24h) on the levels of the acetylated proteins and acetylated H3 Lys24 (H3K24ac) in the neocortex and hippocampus of rats were studied. SH caused global repression of the acetylation processes in the neocortex (layers II-III, V) and hippocampus (CA1, CA3) by 3-24h, and this effect was prevented by the preconditioning. Moreover, hypoxic preconditioning remarkably increased the acetylation of H3K24 in response to SH in the brain areas examined. The preconditioning hypoxia without subsequent SH also stimulated acetylation processes in the neocortex and hippocampus. The moderately enhanced expression of the acetylated proteins in the preconditioned rats was maintained for 24h, whereas acetylation of H3K24 was intense but transient, peaked at 3h. The novel data obtained in the present study indicate that large activation of the acetylation processes, in particular acetylation of histones might be essential for the development of brain hypoxic tolerance. Copyright © 2015 Elsevier GmbH. All rights reserved.
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The pattern of traumatic brain injuries: a country undergoing rapid development.
Bener, Abdulbari; Omar, Azhar O Kh; Ahmad, Amal E; Al-Mulla, Fatma H; Abdul Rahman, Yassir S
2010-02-01
Traumatic brain injuries (TBIs) remain an important public health problem in most industrial developed and especially in developing countries. This may also result in temporary or permanent disability. The aim of this study was to examine the trends in the distribution of traumatic brain injuries by gender, age, severity of injury and outcome and describe the incidence in the injury patterns. This is a retrospective, descriptive, hospital-based study that included all cases of TBI during the period from January 2003 to December 2007. This study is a retrospective analysis of 1919 patients with traumatic brain injury attended and treated at the Accident and Emergency Department of the Hamad General Hospital and other Trauma Centers of the Hamad Medical Corporation. Details of all TBI cases were extracted from the database of the Emergency Medical Services (EMS). Severity of TBI was assessed by Glasgow Coma Scale (GCS). This study was based on 1919 patients suffering from traumatic brain injury, where 154 died and 97 (5.1%) of them died in the intensive care unit. The number of TBI cases increased remarkably in 2007 by 69.7%. However, the incidence rate was nearly stable across the years (4.2-4.9/10 000 population). Of the total TBI cases, the majority of them were non-Qataris (72.7%) and men (88.6%). There was a significant increase in number of TBI cases between 2003 and 2007 in terms of age group (p = 0.003), nationality (p = 0.004) and severity of injuries (p = 0.05). The highest peak rate of TBI cases was observed among the population over 65 years old, followed by 15-24 year olds. Falls caused most TBIs in the 1-14 years age group, road traffic accidents in the age group 15-24 years and sports and recreation in the age group 25-34 years. The present study findings revealed that traumatic brain injury is a major public health problem, especially among young adults and older people. Although there was a sharp increase found in the number of TBI cases, the incidence rate of TBI took a stable trend during the study period.
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Shiue, Grace G; Choi, Seok-Rye; Fang, Ping; Hou, Catherine; Acton, Paul D; Cardi, Chris; Saffer, Janet R; Greenberg, Joel H; Karp, Joel S; Kung, Hank F; Shiue, Chyng-Yann
2003-12-01
There has been considerable interest in the development of PET radioligands that are useful for imaging serotonin transporter (SERT) in the living human brain. For the last decade, (11)C-(+)McN5652 has been the most promising PET agent for studying SERT in humans. However, this agent has some limitations. Recently, a new promising SERT PET radioligand, 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile, has been reported. We recently reported the synthesis of a new (18)F-labeled SERT PET radioligand, N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-(18)F-ADAM), which may have advantages over (11)C-labeled radioligands. The purpose of this study was to evaluate this newly developed (18)F-labeled PET radioligand as a promising agent for studying SERT in the living human brain. This agent was evaluated by studying its in vitro binding to different monoamine transporters, its in vivo biodistributions in rats, its integrity and pharmacologic profiles in rat brain, and its distribution in a female baboon brain. In vitro binding assays showed that 4-F-ADAM displayed high affinity to SERT sites (inhibition constant = 0.081 nmol/L, using membrane preparations of LLC-PK1 cells expressing the specific transporter) and showed more than 1,000- and 28,000-fold selectivity for SERT over norepinephrine transporter and dopamine transporter, respectively. Biodistribution of 4-(18)F-ADAM in rats showed a high initial uptake and slow clearance in the brain (2.13%, 1.90%, and 0.95% injected dose per organ at 2, 30, and 60 min after intravenous injection, respectively), with the specific binding peaking at 2 h after injection (hypothalamus/cerebellum = 12.49). The uptake in blood, muscle, lung, kidney, and liver was also initially high but cleared rapidly. The radioactivity in the femur increases with time for 4-(18)F-ADAM, indicating that in vivo defluorination may occur. In vivo metabolism studies in rats showed that 4-(18)F-ADAM was not metabolized in rat brain (>96% of radioactivity was recovered as parent compound at 1 h after injection). However, it metabolized rapidly in the blood. Less than 7% of the radioactivity recovered from plasma was the parent compound, with the majority of radioactivity in the plasma not extractable by ethyl acetate. Blocking studies showed significant decreases in the uptake of 4-(18)F-ADAM in the brain regions (hypothalamus, hippocampus, and striatum) where SERT concentrations are high when rats were pretreated with (+)McN5652 (2 mg/kg 5 min before intravenous injection of 4-(18)F-ADAM). However, changes in the uptake of 4-(18)F-ADAM in these brain regions were less significant when rats were pretreated with either methylphenidate or nisoxetine. The baboon study showed that uptake of 4-(18)F-ADAM in the midbrain peaked at approximately 1 h after injection and then declined slowly. The ratios of the radioactivity in the midbrain to that in the cerebellum (where the concentration of SERT is low) at 2 and 3 h after injection were 3.2 and 4.2, respectively. 4-(18)F-ADAM is suitable as a PET radioligand for studying SERT in the living brain. Further characterization of this new radioligand in humans is warranted.
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Functional Brain Connectivity as a New Feature for P300 Speller.
Kabbara, Aya; Khalil, Mohamad; El-Falou, Wassim; Eid, Hassan; Hassan, Mahmoud
2016-01-01
The brain is a large-scale complex network often referred to as the "connectome". Cognitive functions and information processing are mainly based on the interactions between distant brain regions. However, most of the 'feature extraction' methods used in the context of Brain Computer Interface (BCI) ignored the possible functional relationships between different signals recorded from distinct brain areas. In this paper, the functional connectivity quantified by the phase locking value (PLV) was introduced to characterize the evoked responses (ERPs) obtained in the case of target and non-targets visual stimuli. We also tested the possibility of using the functional connectivity in the context of 'P300 speller'. The proposed approach was compared to the well-known methods proposed in the state of the art of "P300 Speller", mainly the peak picking, the area, time/frequency based features, the xDAWN spatial filtering and the stepwise linear discriminant analysis (SWLDA). The electroencephalographic (EEG) signals recorded from ten subjects were analyzed offline. The results indicated that phase synchrony offers relevant information for the classification in a P300 speller. High synchronization between the brain regions was clearly observed during target trials, although no significant synchronization was detected for a non-target trial. The results showed also that phase synchrony provides higher performance than some existing methods for letter classification in a P300 speller principally when large number of trials is available. Finally, we tested the possible combination of both approaches (classical features and phase synchrony). Our findings showed an overall improvement of the performance of the P300-speller when using Peak picking, the area and frequency based features. Similar performances were obtained compared to xDAWN and SWLDA when using large number of trials.
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Giapitzakis, Ioannis-Angelos; Avdievich, Nikolai; Henning, Anke
2018-08-01
Macromolecular resonances (MM) arise mainly from cytosolic proteins and overlap with metabolites, influencing metabolite quantification. Macromolecules can serve as valuable biomarkers for diseases and pathologies. The objectives of this study were to characterize MM at 9.4T in the human brain (occipital and left parietal lobe) and to describe the RF coil setup used for MM acquisition in the two regions. An adiabatic inversion pulse was optimised for metabolite nulling at 9.4T using double inversion recovery and was combined for the first time with metabolite cycled (MC) semi-LASER and appropriate coil configuration. MM spectra (seven volunteers) from two brain locations were averaged and smoothed creating MM templates, which were then parametrized using simulated Voigt-shaped lines within LCModel. Quantification was performed on individual data sets, including corrections for different tissue composition and the T 1 and T 2 relaxation of water. Our coil configuration method resulted in efficient B1+ (>30 T/√kW) for both brain regions. The 15 MM components were detected and quantified in MM baselines of the two brain areas. No significant differences in concentration levels of MM between different regions were found. Two new MM peaks were reported (M7 & M8). Double inversion, which was combined with MC semi-LASER, enabled the acquisition of high spectral resolution MM spectra for both brain regions at 9.4T. The 15 MM components were detected and quantified. Two new MM peaks were reported for the first time (M7 & M8) and preliminarily assigned to β-methylene protons of aspartyl-groups. Magn Reson Med 80:462-473, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.
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NASA Astrophysics Data System (ADS)
Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; An Nguyen, Thien; Alfano, Robert R.
2014-06-01
Two-photon (2P) excitation of the second singlet (S) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S2 state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.
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Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; Nguyen, Thien An; Alfano, Robert R
2014-06-01
Two-photon (2P) excitation of the second singlet (S₂) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S₂ state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S₂ state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.
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NASA Astrophysics Data System (ADS)
Haj-Hosseini, Neda; Lowndes, Shannely; Salerud, Göran; Wårdell, Karin
2011-03-01
Fluorescence guidance in brain tumor resection is performed intra-operatively where bleeding is included. When using fiber-optical probes, the transmission of light to and from the tissue is totally or partially blocked if a small amount of blood appears in front of the probe. Sometimes even after rinsing with saline, the remnant blood cells on the optical probe head, disturb the measurements. In such a case, the corresponding spectrum cannot be reliably quantified and is therefore discarded. The optimal case would be to calculate and take out the blood effect systematically from the collected signals. However, the first step is to study the pattern of blood interference in the fluorescence spectrum. In this study, a fiber-optical based fluorescence spectroscopy system with a laser excitation light of 405 nm (1.4 J/cm2) was used during fluorescence guided brain tumor resection using 5-aminolevulinic acid (5-ALA). The blood interference pattern in the fluorescence spectrum collected from the brain was studied in two patients. The operation situation was modeled in the laboratory by placing blood drops from the finger tip on the skin of forearm and the data was compared to the brain in vivo measurements. Additionally, a theoretical model was developed to simulate the blood interference pattern on the skin autofluorescence. The blood affects the collected fluorescence intensity and leaves traces of oxy and deoxy-hemoglobin absorption peaks. According to the developed theoretical model, the autofluorescence signal is considered to be totally blocked by an approximately 500 μm thick blood layer.
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Phosphorus NMR of isolated perfused morris hepatomas
DOE Office of Scientific and Technical Information (OSTI.GOV)
Graham, R.A.; Meyer, R.A.; Brown, T.R.
1986-03-05
The authors are developing techniques for the study of perfused solid tumors by NMR. Tissue-isolated solid hepatomas were grown to 1-2 cm diameter as described previously. The arterial supply was isolated and the tumors perfused (0.5 - 1.0 ml/min) in vitro at 25 C with a 15% suspension of red blood cells in Krebs-Henseliet solution. /sup 31/P-NMR spectra were acquired at 162 MHz in a specially-designed NMR probe using a solenoidal coil. Intracellular pH (monitored from the chemical shift of inorganic phosphate) and ATP levels were stable for up to 6 hrs during perfusion. During 30 min of global ischemia,more » ATP decreased by 75% and pH fell from 7.0 to 6.7. These changes were reversed by 1 hr reperfusion. In addition to ATP and phosphate, the spectra included a large resonance due to phosphomonoesters, as well as peaks consistent with glycerylphosphocholine, glyceryl-phosphoethanolamine, phosphocreatine, NAD, and UDPG. However, the most novel feature of the spectra was the presence of an unidentified peak in the phosphonate region (+ 16.9 ppm). The peak was not present in spectra of muscle, liver, brain, kidney, or fat tissues excised from the same animals. They are presently attempting to identify the compound that gives rise to this peak and to establish its metabolic origin.« less
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Smart, N A; Meyer, T; Butterfield, J A; Faddy, S C; Passino, C; Malfatto, G; Jonsdottir, S; Sarullo, F; Wisloff, U; Vigorito, C; Giallauria, F
2012-06-01
Brain natriuretic peptide (BNP) predicts exercise performance and exercise training may modulate BNP and its N-terminal portion (NT-pro-BNP), we therefore conducted an individual patient analysis of exercise training effects on BNP and NT-pro-BNP. To use an individual patient meta-analysis to relate changes in BNP, NT-pro-BNP, and peak VO(2); to link these changes to volume parameters of exercise training programmes (intensity etc.); and to identify patient characteristics likely to lead to greater improvements in BNP, NT-pro-BNP, and peak VO(2). Individual patient meta-analysis. A systematic search was conducted of Medline (Ovid), Embase.com, Cochrane Central Register of Controlled Trials, and CINAHL (until July 2008) to identify randomized controlled trials of aerobic and/or resistance exercise training in systolic heart failure patients measuring BNP and/or NT-pro-BNP. Primary outcome measures were change in BNP, NT-pro-BNP, and peak VO2. Subanalyses were conducted to identify (1) patient groups that benefit most and (2) exercise programme parameters enhancing favourable changes in primary outcome measures. Ten randomized controlled studies measuring BNP or NT-pro-BNP met eligibility criteria, authors provided individual patient data for 565 patients (313 exercise and 252 controls). Exercise training had favourable effects on BNP (-28.3%, p < 0.0001), NT-pro-BNP (-37.4%, p = < 0.0001), and peak VO(2) (17.8%, p < 0.0001). The analysis showed a significant change in primary outcome measures; moreover, change in BNP (r = -0.31, p < 0.0001) and NT-pro-BNP (r = -0.22, p < 0.0001) were correlated with peak VO(2) change. Exercise training has favourable effects on BNP, NT-pro-BNP, and peak VO(2) in heart failure patients and BNP/NT-pro-BNP changes were correlated with peak VO(2) changes.
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Salvadego, Desy; Lazzer, Stefano; Marzorati, Mauro; Porcelli, Simone; Rejc, Enrico; Simunic, Bostjan; Pisot, Rado; di Prampero, Pietro Enrico; Grassi, Bruno
2011-12-01
A functional evaluation of skeletal muscle oxidative metabolism during dynamic knee extension (KE) incremental exercises was carried out following a 35-day bed rest (BR) (Valdoltra 2008 BR campaign). Nine young male volunteers (age: 23.5 ± 2.2 yr; mean ± SD) were evaluated. Pulmonary gas exchange, heart rate and cardiac output (by impedance cardiography), skeletal muscle (vastus lateralis) fractional O(2) extraction, and brain (frontal cortex) oxygenation (by near-infrared spectroscopy) were determined during incremental KE. Values at exhaustion were considered "peak". Peak heart rate (147 ± 18 beats/min before vs. 146 ± 17 beats/min after BR) and peak cardiac output (17.8 ± 3.3 l/min before vs. 16.1 ± 1.8 l/min after BR) were unaffected by BR. As expected, brain oxygenation did not decrease during KE. Peak O(2) uptake was lower after vs. before BR, both when expressed as liters per minute (0.99 ± 0.17 vs. 1.26 ± 0.27) and when normalized per unit of quadriceps muscle mass (46.5 ± 6.4 vs. 56.9 ± 11.0 ml·min(-1)·100 g(-1)). Skeletal muscle peak fractional O(2) extraction, expressed as a percentage of the maximal values obtained during a transient limb ischemia, was lower after (46.3 ± 12.1%) vs. before BR (66.5 ± 11.2%). After elimination, by the adopted exercise protocol, of constraints related to cardiovascular O(2) delivery, a decrease in peak O(2) uptake and muscle peak capacity of fractional O(2) extraction was found after 35 days of BR. These findings suggest a substantial impairment of oxidative function at the muscle level, "downstream" with respect to bulk blood flow to the exercising muscles, that is possibly at the level of blood flow distribution/O(2) utilization inside the muscle, peripheral O(2) diffusion, and intracellular oxidative metabolism.
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Increased expression and processing of caspase-12 after traumatic brain injury in rats.
Larner, Stephen F; Hayes, Ronald L; McKinsey, Deborah M; Pike, Brian R; Wang, Kevin K W
2004-01-01
Traumatic brain injury (TBI) disrupts tissue homeostasis resulting in pathological apoptotic activation. Recently, caspase-12 was reported to be induced and activated by the unfolded protein response following excess endoplasmic reticulum (ER) stress. This study examined rat caspase-12 expression using the controlled cortical impact TBI model. Immunoblots of fractionalized cell lysates found elevated caspase-12 proform (approximately 60 kDa) and processed form (approximately 12 kDa), with peak induction observed within 24 h post-injury in the cortex (418% and 503%, respectively). Hippocampus caspase-12 proform induction peaked at 24 h post-injury (641%), while processed form induction peaked at 6 h (620%). Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis confirmed elevated caspase-12 mRNA levels after TBI. Injury severity (1.0, 1.2 or 1.6 mm compression) was associated with increased caspase-12 mRNA expression, peaking at 5 days in the cortex (657%, 651% and 1259%, respectively) and 6 h in the hippocampus (435%, 451% and 460%, respectively). Immunohistochemical analysis revealed caspase-12 induction in neurons in both the cortex and hippocampus as well as in astrocytes at the contusion site. This is the first report of increased expression of caspase-12 following TBI. Our results suggest that the caspase-12-mediated ER apoptotic pathway may play a role in rat TBI pathology independent of the receptor- or mitochondria-mediated apoptotic pathways.
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Isolation, properties and P content of the human brain myosin.
Fazekas, S; Ováry, I; Horváth, E; Székessy-Hermann, V; Juhász, P
1982-01-01
KCl-, and NaCl-myosins were prepared from different parts of the central nervous system (CNS). Throughout these experiments P and lipid contents were higher in NaCl-myosins than in KCl-preparations. Both KCl-, and NaCl-myosins have increased lipid and P contents compared with skeletal muscle myosins. When the specimens were separated by a molecular sieve, it was found by chromatographic technique on Sepharose 4B column that the cerebral and cerebellar myosins were composed of two fractions of different molecular mass while the brain stem and spinal cord myosins revealed only a single peak. The myosin fractions' Ca-ATPase activity could be augmented by rabbit muscle actin. The myosin preparations developed filamentous systems and aggregates which could be shown by scanning electron microscopy. All the CNS-myosin preparations could be phosphorylated; however, they were saturated to a different degree and were influenced by the presence or absence of serotonin. The kinetic studies revealed that the phosphate saturation of the brain stem, cerebellar and cerebral myosins depended on the ATP concentration and incubation time. The alkaline hydrolysates of lipid-free human brain myosin preparations contained amino acid phosphates, P-Arg, P-Lys and P-His in different amounts depending on their sources. In response to a phosphorylating mixture only the amount of P-Arg was elevated in the cerebral myosins, P-Arg and P-His in the brain stem preparations, and P-Arg, P-His and the amounts of unidentified compounds in the cerebellar ones.
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Silva, Aniélen D; Bottari, Nathieli B; do Carmo, Guilherme M; Baldissera, Matheus D; Souza, Carine F; Machado, Vanessa S; Morsch, Vera M; Schetinger, Maria Rosa C; Mendes, Ricardo E; Monteiro, Silvia G; Da Silva, Aleksandro S
2018-01-01
Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.
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Treatment of Glioma Using neuroArm Surgical System
2016-01-01
The use of robotic technology in the surgical treatment of brain tumour promises increased precision and accuracy in the performance of surgery. Robotic manipulators may allow superior access to narrow surgical corridors compared to freehand or conventional neurosurgery. This paper reports values and ranges of tool-tissue interaction forces during the performance of glioma surgery using an MR compatible, image-guided neurosurgical robot called neuroArm. The system, capable of microsurgery and stereotaxy, was used in the surgical resection of glioma in seven cases. neuroArm is equipped with force sensors at the end-effector allowing quantification of tool-tissue interaction forces and transmits force of dissection to the surgeon sited at a remote workstation that includes a haptic interface. Interaction forces between the tool tips and the brain tissue were measured for each procedure, and the peak forces were quantified. Results showed maximum and minimum peak force values of 2.89 N (anaplastic astrocytoma, WHO grade III) and 0.50 N (anaplastic oligodendroglioma, WHO grade III), respectively, with the mean of peak forces varying from case to case, depending on type of the glioma. Mean values of the peak forces varied in range of 1.27 N (anaplastic astrocytoma, WHO grade III) to 1.89 N (glioblastoma with oligodendroglial component, WHO grade IV). In some cases, ANOVA test failed to reject the null hypothesis of equality in means of the peak forces measured. However, we could not find a relationship between forces exerted to the pathological tissue and its size, type, or location. PMID:27314044
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Jayakumar, Archana; Pfister, Bryan J.; Santhakumar, Vijayalakshmi
2015-01-01
Traumatic brain injury (TBI) can occur from physical trauma from a wide spectrum of insults ranging from explosions to falls. The biomechanics of the trauma can vary in key features, including the rate and magnitude of the insult. Although the effect of peak injury pressure on neurological outcome has been examined in the fluid percussion injury (FPI) model, it is unknown whether differences in rate of rise of the injury waveform modify cellular and physiological changes after TBI. Using a programmable FPI device, we examined juvenile rats subjected to a constant peak pressure at two rates of injury: a standard FPI rate of rise and a faster rate of rise to the same peak pressure. Immediate postinjury assessment identified fewer seizures and relatively brief loss of consciousness after fast-rise injuries than after standard-rise injuries at similar peak pressures. Compared with rats injured at standard rise, fewer silver-stained injured neuronal profiles and degenerating hilar neurons were observed 4-6 hr after fast-rise FPI. However, 1 week postinjury, both fast- and standard-rise FPI resulted in hilar cell loss and enhanced perforant path-evoked granule cell field excitability compared with sham controls. Notably, the extent of neuronal loss and increase in dentate excitability were not different between rats injured at fast and standard rates of rise to peak pressure. Our data indicate that reduced cellular damage and improved immediate neurological outcome after fast rising primary concussive injuries mask the severity of the subsequent cellular and neurophysiological pathology and may be unreliable as a predictor of prognosis. PMID:24799156
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The cytokine temporal profile in rat cortex after controlled cortical impact
Dalgard, Clifton L.; Cole, Jeffrey T.; Kean, William S.; Lucky, Jessica J.; Sukumar, Gauthaman; McMullen, David C.; Pollard, Harvey B.; Watson, William D.
2012-01-01
Cerebral inflammatory responses may initiate secondary cascades following traumatic brain injury (TBI). Changes in the expression of both cytokines and chemokines may activate, regulate, and recruit innate and adaptive immune cells associated with secondary degeneration, as well as alter a host of other cellular processes. In this study, we quantified the temporal expression of a large set of inflammatory mediators in rat cortical tissue after brain injury. Following a controlled cortical impact (CCI) on young adult male rats, cortical and hippocampal tissue of the injured hemisphere and matching contralateral material was harvested at early (4, 12, and 24 hours) and extended (3 and 7 days) time points post-procedure. Naïve rats that received only anesthesia were used as controls. Processed brain homogenates were assayed for chemokine and cytokine levels utilizing an electrochemiluminescence-based multiplex ELISA platform. The temporal profile of cortical tissue samples revealed a multi-phasic injury response following brain injury. CXCL1, IFN-γ, TNF-α levels significantly peaked at four hours post-injury compared to levels found in naïve or contralateral tissue. CXCL1, IFN-γ, and TNF-α levels were then observed to decrease at least 3-fold by 12 hours post-injury. IL-1β, IL-4, and IL-13 levels were also significantly elevated at four hours post-injury although their expression did not decrease more than 3-fold for up to 24 hours post-injury. Additionally, IL-1β and IL-4 levels displayed a biphasic temporal profile in response to injury, which may suggest their involvement in adaptive immune responses. Interestingly, peak levels of CCL2 and CCL20 were not observed until after four hours post-injury. CCL2 levels in injured cortical tissue were significantly higher than peak levels of any other inflammatory mediator measured, thus suggesting a possible use as a biomarker. Fully elucidating chemokine and cytokine signaling properties after brain injury may provide increased insight into a number of secondary cascade events that are initiated or regulated by inflammatory responses. PMID:22291617
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The cytokine temporal profile in rat cortex after controlled cortical impact.
Dalgard, Clifton L; Cole, Jeffrey T; Kean, William S; Lucky, Jessica J; Sukumar, Gauthaman; McMullen, David C; Pollard, Harvey B; Watson, William D
2012-01-01
Cerebral inflammatory responses may initiate secondary cascades following traumatic brain injury (TBI). Changes in the expression of both cytokines and chemokines may activate, regulate, and recruit innate and adaptive immune cells associated with secondary degeneration, as well as alter a host of other cellular processes. In this study, we quantified the temporal expression of a large set of inflammatory mediators in rat cortical tissue after brain injury. Following a controlled cortical impact (CCI) on young adult male rats, cortical and hippocampal tissue of the injured hemisphere and matching contralateral material was harvested at early (4, 12, and 24 hours) and extended (3 and 7 days) time points post-procedure. Naïve rats that received only anesthesia were used as controls. Processed brain homogenates were assayed for chemokine and cytokine levels utilizing an electrochemiluminescence-based multiplex ELISA platform. The temporal profile of cortical tissue samples revealed a multi-phasic injury response following brain injury. CXCL1, IFN-γ, TNF-α levels significantly peaked at four hours post-injury compared to levels found in naïve or contralateral tissue. CXCL1, IFN-γ, and TNF-α levels were then observed to decrease at least 3-fold by 12 hours post-injury. IL-1β, IL-4, and IL-13 levels were also significantly elevated at four hours post-injury although their expression did not decrease more than 3-fold for up to 24 hours post-injury. Additionally, IL-1β and IL-4 levels displayed a biphasic temporal profile in response to injury, which may suggest their involvement in adaptive immune responses. Interestingly, peak levels of CCL2 and CCL20 were not observed until after four hours post-injury. CCL2 levels in injured cortical tissue were significantly higher than peak levels of any other inflammatory mediator measured, thus suggesting a possible use as a biomarker. Fully elucidating chemokine and cytokine signaling properties after brain injury may provide increased insight into a number of secondary cascade events that are initiated or regulated by inflammatory responses.
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Stagni, Fiorenza; Giacomini, Andrea; Emili, Marco; Trazzi, Stefania; Guidi, Sandra; Sassi, Martina; Ciani, Elisabetta; Rimondini, Roberto; Bartesaghi, Renata
2016-10-01
Cognitive disability is an unavoidable feature of Down syndrome (DS), a genetic disorder due to the triplication of human chromosome 21. DS is associated with alterations of neurogenesis, neuron maturation and connectivity that are already present at prenatal life stages. Recent evidence shows that pharmacotherapies can have a large impact on the trisomic brain provided that they are administered perinatally. Epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, performs many actions in the brain, including inhibition of DYRK1A, a kinase that is over-expressed in the DS brain and contributes to the DS phenotype. Young adults with DS treated with EGCG exhibit some cognitive benefits, although these effects disappear with time. We deemed it extremely important, however, to establish whether treatment with EGCG at the initial stages of brain development leads to plastic changes that outlast treatment cessation. In the current study, we exploited the Ts65Dn mouse model of DS in order to establish whether pharmacotherapy with EGCG during peak of neurogenesis in the hippocampal dentate gyrus (DG) enduringly restores hippocampal development and memory performance. Euploid and Ts65Dn mice were treated with EGCG from postnatal day 3 (P3) to P15. The effects of treatment were examined at its cessation (at P15) or after one month (at P45). We found that at P15 treated trisomic pups exhibited restoration of neurogenesis, total hippocampal granule cell number and levels of pre- and postsynaptic proteins in the DG, hippocampus and neocortex. However, at P45 none of these effects were still present, nor did treated Ts65Dn mice exhibit any improvement in hippocampus-dependent tasks. These findings show that treatment with EGCG carried out in the neonatal period rescues numerous trisomy-linked brain alterations. However, even during this, the most critical time window for hippocampal development, EGCG does not elicit enduring effects on the hippocampal physiology. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
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Locomotor activity and tissue levels following acute ...
Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., λ-cyhalothrin) as well as enriched active isomers (e.g., γ-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of λ- and γ-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5 h after oral gavage dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for γ-cyhalothrin was lower than for λ-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the γ-isomer (1.29 mg/kg) compared to λ-cyhalothrin (2.65 mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of γ-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While γ-cyhalothrin was 2-fold more potent based on administ
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Lereim, Ragnhild Reehorst; Oveland, Eystein; Xiao, Yichuan; Torkildsen, Øivind; Wergeland, Stig; Myhr, Kjell-Morten; Sun, Shao-Cong; Berven, Frode S
2016-09-01
The ubiquitin ligase Peli1 has previously been suggested as a potential treatment target in multiple sclerosis. In the multiple sclerosis disease model, experimental autoimmune encephalomyelitis, Peli1 knock-out led to less activated microglia and less inflammation in the central nervous system. Despite being important in microglia, Peli1 expression has also been detected in glial and neuronal cells. In the present study the overall brain proteomes of Peli1 knock-out mice and wild-type mice were compared prior to experimental autoimmune encephalomyelitis induction, at onset of the disease and at disease peak. Brain samples from the frontal hemisphere, peripheral from the extensive inflammatory foci, were analyzed using TMT-labeling of sample pools, and the discovered proteins were verified in individual mice using label-free proteomics. The greatest proteomic differences between Peli1 knock-out and wild-type mice were observed at the disease peak. In Peli1 knock-out a higher degree of antigen presentation, increased activity of adaptive and innate immune cells and alterations to proteins involved in iron metabolism were observed during experimental autoimmune encephalomyelitis. These results unravel global effects to the brain proteome when abrogating Peli1 expression, underlining the importance of Peli1 as a regulator of the immune response also peripheral to inflammatory foci during experimental autoimmune encephalomyelitis. The proteomics data is available in PRIDE with accession PXD003710.
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Sheng, Min; Liu, Peiying; Mao, Deng; Ge, Yulin; Lu, Hanzhang
2017-01-01
A better understanding of the effect of oxygen on brain electrophysiological activity may provide a more mechanistic insight into clinical studies that use oxygen treatment in pathological conditions, as well as in studies that use oxygen to calibrate functional magnetic resonance imaging (fMRI) signals. This study applied electroencephalography (EEG) in healthy subjects and investigated how high a concentration of oxygen in inhaled air (i.e., normobaric hyperoxia) alters brain activity under resting-state and task-evoked conditions. Study 1 investigated its impact on resting EEG and revealed that hyperoxia suppressed α (8-13Hz) and β (14-35Hz) band power (by 15.6±2.3% and 14.1±3.1%, respectively), but did not change the δ (1-3Hz), θ (4-7Hz), and γ (36-75Hz) bands. Sham control experiments did not result in such changes. Study 2 reproduced these findings, and, furthermore, examined the effect of hyperoxia on visual stimulation event-related potentials (ERP). It was found that the main peaks of visual ERP, specifically N1 and P2, were both delayed during hyperoxia compared to normoxia (P = 0.04 and 0.02, respectively). In contrast, the amplitude of the peaks did not show a change. Our results suggest that hyperoxia has a pronounced effect on brain neural activity, for both resting-state and task-evoked potentials.
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Sheng, Min; Liu, Peiying; Mao, Deng; Ge, Yulin
2017-01-01
A better understanding of the effect of oxygen on brain electrophysiological activity may provide a more mechanistic insight into clinical studies that use oxygen treatment in pathological conditions, as well as in studies that use oxygen to calibrate functional magnetic resonance imaging (fMRI) signals. This study applied electroencephalography (EEG) in healthy subjects and investigated how high a concentration of oxygen in inhaled air (i.e., normobaric hyperoxia) alters brain activity under resting-state and task-evoked conditions. Study 1 investigated its impact on resting EEG and revealed that hyperoxia suppressed α (8-13Hz) and β (14-35Hz) band power (by 15.6±2.3% and 14.1±3.1%, respectively), but did not change the δ (1-3Hz), θ (4-7Hz), and γ (36-75Hz) bands. Sham control experiments did not result in such changes. Study 2 reproduced these findings, and, furthermore, examined the effect of hyperoxia on visual stimulation event-related potentials (ERP). It was found that the main peaks of visual ERP, specifically N1 and P2, were both delayed during hyperoxia compared to normoxia (P = 0.04 and 0.02, respectively). In contrast, the amplitude of the peaks did not show a change. Our results suggest that hyperoxia has a pronounced effect on brain neural activity, for both resting-state and task-evoked potentials. PMID:28464001
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The effect of brain injury on the inflammatory response following severe trauma.
Lustenberger, T; Kern, M; Relja, B; Wutzler, S; Störmann, P; Marzi, I
2016-03-01
The inflammatory response is an important part of the pathophysiology of severe injury and, in particular, of severe traumatic brain injury (TBI). This study evaluates the inflammatory course following major trauma and focuses on the effect of severe TBI on inflammatory markers. This was a retrospective analysis of prospectively collected data in 123 severely injured (ISS ≥16) trauma patients. The study cohort was divided into patients with isolated TBI (Head AIS ≥3, all other AIS <3), polytraumatized patients with severe TBI (Head AIS ≥3; AIS of other body area ≥3; Polytrauma+TBI) and polytraumatized patients without TBI (Head AIS <3; Polytrauma). Levels of inflammatory markers (Interleukin-6 [IL-6], C-reactive Protein [CRP], leukocytes) measured upon arrival and through hospital days 1-3 were compared between the groups. On admission and through hospital day 3, IL-6 levels were significantly different between the 3 groups (admission: isolated TBI vs. Polytrauma+TBI vs. Polytrauma; 94±16 vs. 149±20 vs. 245±50pg/mL; p<0.05). Interleukin-6 levels peaked on hospital day 1 and declined thereafter. C-reactive protein and leukocyte counts were not significantly different between the cohorts on arrival and peaked on hospital day 2 and 1, respectively. In patients with severe TBI, admission IL-6 levels significantly predicted the development of septic complications (ROC analysis, AUC: 0.88, p=0.001, 95% CI: 0.79-0.97) and multiple organ dysfunction (ROC analysis, AUC: 0.83, p=0.001, 95% CI: 0.69-0.96). Severe TBI reduced the inflammatory response following trauma. Significant correlations between admission IL-6 values and the development of MOF, sepsis and the neurological outcome were found in patients with TBI. Copyright © 2015 Elsevier GmbH. All rights reserved.
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Williams, Anthony J; Wei, Hans H; Dave, Jitendra R; Tortella, Frank C
2007-01-01
Background Neuroinflammation following acute brain trauma is considered to play a prominent role in both the pathological and reconstructive response of the brain to injury. Here we characterize and contrast both an acute and delayed phase of inflammation following experimental penetrating ballistic brain injury (PBBI) in rats out to 7 days post-injury. Methods Quantitative real time PCR (QRT-PCR) was used to evaluate changes in inflammatory gene expression from the brain tissue of rats exposed to a unilateral frontal PBBI. Brain histopathology was assessed using hematoxylin and eosin (H&E), silver staining, and immunoreactivity for astrocytes (GFAP), microglia (OX-18) and the inflammatory proteins IL-1β and ICAM-1. Results Time course analysis of gene expression levels using QRT-PCR indicated a peak increase during the acute phase of the injury between 3–6 h for the cytokines TNF-α (8–11 fold), IL-1β (11–13 fold), and IL-6 (40–74 fold) as well as the cellular adhesion molecules VCAM (2–3 fold), ICAM-1 (7–15 fold), and E-selectin (11–13 fold). Consistent with the upregulation of pro-inflammatory genes, peripheral blood cell infiltration was a prominent post-injury event with peak levels of infiltrating neutrophils (24 h) and macrophages (72 h) observed throughout the core lesion. In regions of the forebrain immediately surrounding the lesion, strong immunoreactivity for activated astrocytes (GFAP) was observed as early as 6 h post-injury followed by prominent microglial reactivity (OX-18) at 72 h and resolution of both cell types in cortical brain regions by day 7. Delayed thalamic inflammation (remote from the primary lesion) was also observed as indicated by both microglial and astrocyte reactivity (72 h to 7 days) concomitant with the presence of fiber degeneration (silver staining). Conclusion In summary, PBBI induces both an acute and delayed neuroinflammatory response occurring in distinct brain regions, which may provide useful diagnostic information for the treatment of this type of brain injury. PMID:17605820
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Kimura-Kuroda, Junko; Komuta, Yukari; Kuroda, Yoichiro; Hayashi, Masaharu; Kawano, Hitoshi
2012-01-01
Background Acetamiprid (ACE) and imidacloprid (IMI) belong to a new, widely used class of pesticide, the neonicotinoids. With similar chemical structures to nicotine, neonicotinoids also share agonist activity at nicotinic acetylcholine receptors (nAChRs). Although their toxicities against insects are well established, their precise effects on mammalian nAChRs remain to be elucidated. Because of the importance of nAChRs for mammalian brain function, especially brain development, detailed investigation of the neonicotinoids is needed to protect the health of human children. We aimed to determine the effects of neonicotinoids on the nAChRs of developing mammalian neurons and compare their effects with nicotine, a neurotoxin of brain development. Methodology/Principal Findings Primary cultures of cerebellar neurons from neonatal rats allow for examinations of the developmental neurotoxicity of chemicals because the various stages of neurodevelopment—including proliferation, migration, differentiation, and morphological and functional maturation—can be observed in vitro. Using these cultures, an excitatory Ca2+-influx assay was employed as an indicator of neural physiological activity. Significant excitatory Ca2+ influxes were evoked by ACE, IMI, and nicotine at concentrations greater than 1 µM in small neurons in cerebellar cultures that expressed the mRNA of the α3, α4, and α7 nAChR subunits. The firing patterns, proportion of excited neurons, and peak excitatory Ca2+ influxes induced by ACE and IMI showed differences from those induced by nicotine. However, ACE and IMI had greater effects on mammalian neurons than those previously reported in binding assay studies. Furthermore, the effects of the neonicotinoids were significantly inhibited by the nAChR antagonists mecamylamine, α-bungarotoxin, and dihydro-β-erythroidine. Conclusions/Significance This study is the first to show that ACE, IMI, and nicotine exert similar excitatory effects on mammalian nAChRs at concentrations greater than 1 µM. Therefore, the neonicotinoids may adversely affect human health, especially the developing brain. PMID:22393406
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NASA Astrophysics Data System (ADS)
Zhao, Chunyan; Xu, Shihong; Feng, Chengcheng; Liu, Yifan; Yang, Yang; Wang, Yanfeng; Xiao, Yongshuang; Song, Zongcheng; Liu, Qinghua; Li, Jun
2017-10-01
Turbots (Schophthalmus maximus), one of the most important economic marine flatfish species, fail to undergo final spawning and spermiation naturally under artificial farming conditions. In vertebrates, reproduction is regulated by the brain-pituitary-gonadal axis (BPG-axis), and gonadotropin releasing hormone (GnRH) is one of its key components. Therefore, to better understand the physiology of reproduction in the turbot, three of the genes encoding GnRH subtypes—sbGnRH, cGnRH-II and sGnRH—were cloned and sequenced by isolating the cDNA sequences. The localizations and patterns of expression of their mRNAs were also evaluated during seasonal gonadal development. All three mRNAs were expressed abundantly in the brain; sbGnRH and sGnRH mRNAs were also detected in the gonads and pituitary gland, and sbGnRH expression was much higher than that of sGnRH, indicating the critical role of sbGnRH in regulating the BPG-axis. Moreover, the brain expression patterns of sbGnRH and sGnRH mRNAs showed an increased trend during gonadal development, peaking in mature stages. This indicated the direct regulation of gonadal development by the GnRH system. In addition, cGnRH-II mRNA expression showed no significant variations, suggesting that cGnRH-II is not critically involved in the control of reproduction. Further, the mRNA abundances of the three GnRH forms in the breeding season were significantly higher than those in immature and post-breeding stages in all analyzed brain areas. Therefore, we propose that sbGnRH is the most important hormone for the regulation of reproduction in turbot via the BPG-axis. These results will help in better understanding the reproductive endocrine mechanisms of turbots and lay the groundwork for additional studies aimed at comparing the reproductive physiology of wild individuals with those raised under artificial conditions.
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Teng, Xiaochun; Liu, Yan-Yun; Teng, Weiping; Brent, Gregory A
2018-05-01
Thyroid hormone is critical for normal brain development and acts in a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. Chicken ovalbumin upstream-transcription factor 1 (COUP-TF1), expressed early in neuronal development, is essential to achieve normal brain structure. Thyroid hormone stimulation of gene expression is inversely correlated with the level of COUP-TF1 expression. An in vitro method of differentiating mouse embryonic stem (mES) cells into cortical neurons was utilized to study the influence of COUP-TF1 on thyroid hormone signaling in brain development. mES cells were cultured and differentiated in specific conditioned media, and a high percentage of nestin-positive progenitor neurons in the first stage, and cortical neurons in the second stage, was obtained with characteristic neuronal firing. The number of nestin-positive progenitors, as determined by fluorescence-activated cell sorting analysis, was significantly greater with triiodothyronine (T3) treatment compared to control (p < 0.05). T3 enhanced the expression of cortical neuron marker (Tbr1 and Rc3) mRNAs. After COUP-TF1 knockdown, the number of nestin-positive progenitors was reduced compared to control (p < 0.05), but the number increased with T3 treatment. The mRNA of cortical neuronal gene markers was measured after COUP-TF1 knockdown. In the presence of T3, the peak expression of neuron markers Emx1, Tbr1, Camkiv, and Rc3 mRNA was earlier, at day 18 of differentiation, compared to control cells, at day 22. Furthermore, after COUP-TF1 knockdown, T3 induction of Rc3 and Tbr1 mRNA was significantly enhanced compared to cells expressing COUP-TF1. These results indicate that COUP-TF1 plays an important role in modulating the timing and magnitude of T3-stimulated gene expression required for normal corticogenesis.
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Gamma Oscillations and Visual Binding
NASA Astrophysics Data System (ADS)
Robinson, Peter A.; Kim, Jong Won
2006-03-01
At the root of visual perception is the mechanism the brain uses to analyze features in a scene and bind related ones together. Experiments show this process is linked to oscillations of brain activity in the 30-100 Hz gamma band. Oscillations at different sites have correlation functions (CFs) that often peak at zero lag, implying simultaneous firing, even when conduction delays are large. CFs are strongest between cells stimulated by related features. Gamma oscillations are studied here by modeling mm-scale patchy interconnections in the visual cortex. Resulting predictions for gamma responses to stimuli account for numerous experimental findings, including why oscillations and zero-lag synchrony are associated, observed connections with feature preferences, the shape of the zero-lag peak, and variations of CFs with attention. Gamma waves are found to obey the Schroedinger equation, opening the possibility of cortical analogs of quantum phenomena. Gamma instabilities are tied to observations of gamma activity linked to seizures and hallucinations.
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Wu, Xiaoping; Adriany, Gregor; Ugurbil, Kamil; Van de Moortele, Pierre-Francois
2013-01-01
Successful implementation of homogeneous slice-selective RF excitation in the human brain at 9.4T using 16-channel parallel transmission (pTX) is demonstrated. A novel three-step pulse design method incorporating fast real-time measurement of eddy current induced B0 variations as well as correction of resulting phase errors during excitation is described. To demonstrate the utility of the proposed method, phantom and in-vivo experiments targeting a uniform excitation in an axial slice were conducted using two-spoke pTX pulses. Even with the pre-emphasis activated, eddy current induced B0 variations with peak-to-peak values greater than 4 kHz were observed on our system during the rapid switches of slice selective gradients. This large B0 variation, when not corrected, resulted in drastically degraded excitation fidelity with the coefficient of variation (CV) of the flip angle calculated for the region of interest being large (~ 12% in the phantom and ~ 35% in the brain). By comparison, excitation fidelity was effectively restored, and satisfactory flip angle uniformity was achieved when using the proposed method, with the CV value reduced to ~ 3% in the phantom and ~ 8% in the brain. Additionally, experimental results were in good agreement with the numerical predictions obtained from Bloch simulations. Slice-selective flip angle homogenization in the human brain at 9.4T using 16-channel 3D spoke pTX pulses is achievable despite of large eddy current induced excitation phase errors; correcting for the latter was critical in this success.
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Newman, Mark A; Hirsch, Mark A; Peindl, Richard D; Habet, Nahir A; Tsai, Tobias J; Runyon, Michael S; Huynh, Toan; Zheng, Nigel
2018-06-01
Studies have evaluated the test-re-test reliability of subcomponents of the timed up and-go test in adults by using body-worn inertial sensors. However, studies in children have not been reported in the literature. To evaluate the within-session reliability of subcomponents of a newly developed electronically augmented timed 'upand-go' test (EATUG) in ambulatory children with traumatic brain injury (TBI) and children with typical development (TD). The timed up and go test was administered to twelve consecutive ambulatory children with moderate to severe TBI (6 males and 6 females, age 10.5 ± 1.5 years, range 8-13 years, during inpatient rehabilitation at 27.0 ± 11.8 days following injury) and 10 TD age and sex-matched children (5 males and 5 females, 10.4 ± 1.3 years, range 8-11 years). Participants wore a single chest-mounted inertial measurement sensor package with custom software that measured angular and acceleration velocity and torso flexion and extension angles, while they performed 6 trials of the EATUG test. Measures were derived from the overall time to complete the TUG test, angular velocity and angular displacement data for torso flexion and extension during sit-to-stand and stand-to-sit segments and both mean and peak angular velocities for two turning segments (i.e. turning around a cone and turning-before-sitting). Within-session reliability of the subcomponents of the TUG test for children with TBI assessed by the intra-class correlation coefficient was ICC (1,1) = 0.84, (range 0.82-0.96), and for TD children ICC (1,1) = 0.73, (range 0.53-0.89). Scores on Total Time, maximum torso flexion/extension angle and peak flexion angular velocity during sit-tostand, and peak turn angular velocity for both turns around the cone and turns before sitting were lower for children with TBI than for TD children (p ≤ 0.05). The EATUG test is a reliable measure of physical function in children with TBI who are being discharged from inpatient rehabilitation. Copyright © 2018 Elsevier B.V. All rights reserved.
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Lloyd, John; Conidi, Frank
2016-03-01
Helmets are used for sports, military, and transportation to protect against impact forces and associated injuries. The common belief among end users is that the helmet protects the whole head, including the brain. However, current consensus among biomechanists and sports neurologists indicates that helmets do not provide significant protection against concussion and brain injuries. In this paper the authors present existing scientific evidence on the mechanisms underlying traumatic head and brain injuries, along with a biomechanical evaluation of 21 current and retired football helmets. The National Operating Committee on Standards for Athletic Equipment (NOCSAE) standard test apparatus was modified and validated for impact testing of protective headwear to include the measurement of both linear and angular kinematics. From a drop height of 2.0 m onto a flat steel anvil, each football helmet was impacted 5 times in the occipital area. Skull fracture risk was determined for each of the current varsity football helmets by calculating the percentage reduction in linear acceleration relative to a 140-g skull fracture threshold. Risk of subdural hematoma was determined by calculating the percentage reduction in angular acceleration relative to the bridging vein failure threshold, computed as a function of impact duration. Ranking the helmets according to their performance under these criteria, the authors determined that the Schutt Vengeance performed the best overall. The study findings demonstrated that not all football helmets provide equal or adequate protection against either focal head injuries or traumatic brain injuries. In fact, some of the most popular helmets on the field ranked among the worst. While protection is improving, none of the current or retired varsity football helmets can provide absolute protection against brain injuries, including concussions and subdural hematomas. To maximize protection against head and brain injuries for football players of all ages, the authors propose thresholds for all sports helmets based on a peak linear acceleration no greater than 90 g and a peak angular acceleration not exceeding 1700 rad/sec(2).
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Dynamic correlations between heart and brain rhythm during Autogenic meditation
Kim, Dae-Keun; Lee, Kyung-Mi; Kim, Jongwha; Whang, Min-Cheol; Kang, Seung Wan
2013-01-01
This study is aimed to determine significant physiological parameters of brain and heart under meditative state, both in each activities and their dynamic correlations. Electrophysiological changes in response to meditation were explored in 12 healthy volunteers who completed 8 weeks of a basic training course in autogenic meditation. Heart coherence, representing the degree of ordering in oscillation of heart rhythm intervals, increased significantly during meditation. Relative EEG alpha power and alpha lagged coherence also increased. A significant slowing of parietal peak alpha frequency was observed. Parietal peak alpha power increased with increasing heart coherence during meditation, but no such relationship was observed during baseline. Average alpha lagged coherence also increased with increasing heart coherence during meditation, but weak opposite relationship was observed at baseline. Relative alpha power increased with increasing heart coherence during both meditation and baseline periods. Heart coherence can be a cardiac marker for the meditative state and also may be a general marker for the meditative state since heart coherence is strongly correlated with EEG alpha activities. It is expected that increasing heart coherence and the accompanying EEG alpha activations, heart brain synchronicity, would help recover physiological synchrony following a period of homeostatic depletion. PMID:23914165
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Dynamic correlations between heart and brain rhythm during Autogenic meditation.
Kim, Dae-Keun; Lee, Kyung-Mi; Kim, Jongwha; Whang, Min-Cheol; Kang, Seung Wan
2013-01-01
This study is aimed to determine significant physiological parameters of brain and heart under meditative state, both in each activities and their dynamic correlations. Electrophysiological changes in response to meditation were explored in 12 healthy volunteers who completed 8 weeks of a basic training course in autogenic meditation. Heart coherence, representing the degree of ordering in oscillation of heart rhythm intervals, increased significantly during meditation. Relative EEG alpha power and alpha lagged coherence also increased. A significant slowing of parietal peak alpha frequency was observed. Parietal peak alpha power increased with increasing heart coherence during meditation, but no such relationship was observed during baseline. Average alpha lagged coherence also increased with increasing heart coherence during meditation, but weak opposite relationship was observed at baseline. Relative alpha power increased with increasing heart coherence during both meditation and baseline periods. Heart coherence can be a cardiac marker for the meditative state and also may be a general marker for the meditative state since heart coherence is strongly correlated with EEG alpha activities. It is expected that increasing heart coherence and the accompanying EEG alpha activations, heart brain synchronicity, would help recover physiological synchrony following a period of homeostatic depletion.
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Porcine head response to blast.
Shridharani, Jay K; Wood, Garrett W; Panzer, Matthew B; Capehart, Bruce P; Nyein, Michelle K; Radovitzky, Raul A; Bass, Cameron R 'dale'
2012-01-01
Recent studies have shown an increase in the frequency of traumatic brain injuries related to blast exposure. However, the mechanisms that cause blast neurotrauma are unknown. Blast neurotrauma research using computational models has been one method to elucidate that response of the brain in blast, and to identify possible mechanical correlates of injury. However, model validation against experimental data is required to ensure that the model output is representative of in vivo biomechanical response. This study exposes porcine subjects to primary blast overpressures generated using a compressed-gas shock tube. Shock tube blasts were directed to the unprotected head of each animal while the lungs and thorax were protected using ballistic protective vests similar to those employed in theater. The test conditions ranged from 110 to 740 kPa peak incident overpressure with scaled durations from 1.3 to 6.9 ms and correspond approximately with a 50% injury risk for brain bleeding and apnea in a ferret model scaled to porcine exposure. Instrumentation was placed on the porcine head to measure bulk acceleration, pressure at the surface of the head, and pressure inside the cranial cavity. Immediately after the blast, 5 of the 20 animals tested were apneic. Three subjects recovered without intervention within 30 s and the remaining two recovered within 8 min following respiratory assistance and administration of the respiratory stimulant doxapram. Gross examination of the brain revealed no indication of bleeding. Intracranial pressures ranged from 80 to 390 kPa as a result of the blast and were notably lower than the shock tube reflected pressures of 300-2830 kPa, indicating pressure attenuation by the skull up to a factor of 8.4. Peak head accelerations were measured from 385 to 3845 G's and were well correlated with peak incident overpressure (R(2) = 0.90). One SD corridors for the surface pressure, intracranial pressure (ICP), and head acceleration are presented to provide experimental data for computer model validation.
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Porcine Head Response to Blast
Shridharani, Jay K.; Wood, Garrett W.; Panzer, Matthew B.; Capehart, Bruce P.; Nyein, Michelle K.; Radovitzky, Raul A.; Bass, Cameron R. ‘Dale’
2012-01-01
Recent studies have shown an increase in the frequency of traumatic brain injuries related to blast exposure. However, the mechanisms that cause blast neurotrauma are unknown. Blast neurotrauma research using computational models has been one method to elucidate that response of the brain in blast, and to identify possible mechanical correlates of injury. However, model validation against experimental data is required to ensure that the model output is representative of in vivo biomechanical response. This study exposes porcine subjects to primary blast overpressures generated using a compressed-gas shock tube. Shock tube blasts were directed to the unprotected head of each animal while the lungs and thorax were protected using ballistic protective vests similar to those employed in theater. The test conditions ranged from 110 to 740 kPa peak incident overpressure with scaled durations from 1.3 to 6.9 ms and correspond approximately with a 50% injury risk for brain bleeding and apnea in a ferret model scaled to porcine exposure. Instrumentation was placed on the porcine head to measure bulk acceleration, pressure at the surface of the head, and pressure inside the cranial cavity. Immediately after the blast, 5 of the 20 animals tested were apneic. Three subjects recovered without intervention within 30 s and the remaining two recovered within 8 min following respiratory assistance and administration of the respiratory stimulant doxapram. Gross examination of the brain revealed no indication of bleeding. Intracranial pressures ranged from 80 to 390 kPa as a result of the blast and were notably lower than the shock tube reflected pressures of 300–2830 kPa, indicating pressure attenuation by the skull up to a factor of 8.4. Peak head accelerations were measured from 385 to 3845 G’s and were well correlated with peak incident overpressure (R2 = 0.90). One SD corridors for the surface pressure, intracranial pressure (ICP), and head acceleration are presented to provide experimental data for computer model validation. PMID:22586417
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Zhu, Feng; Kalra, Anil; Saif, Tal; Yang, Zaihan; Yang, King H; King, Albert I
2016-01-01
Traumatic brain injury due to primary blast loading has become a signature injury in recent military conflicts and terrorist activities. Extensive experimental and computational investigations have been conducted to study the interrelationships between intracranial pressure response and intrinsic or 'input' parameters such as the head geometry and loading conditions. However, these relationships are very complicated and are usually implicit and 'hidden' in a large amount of simulation/test data. In this study, a data mining method is proposed to explore such underlying information from the numerical simulation results. The heads of different species are described as a highly simplified two-part (skull and brain) finite element model with varying geometric parameters. The parameters considered include peak incident pressure, skull thickness, brain radius and snout length. Their interrelationship and coupling effect are discovered by developing a decision tree based on the large simulation data-set. The results show that the proposed data-driven method is superior to the conventional linear regression method and is comparable to the nonlinear regression method. Considering its capability of exploring implicit information and the relatively simple relationships between response and input variables, the data mining method is considered to be a good tool for an in-depth understanding of the mechanisms of blast-induced brain injury. As a general method, this approach can also be applied to other nonlinear complex biomechanical systems.
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You, Wanchun; Wang, Zhong; Li, Haiying; Shen, Haitao; Xu, Xiang; Jia, Genlai; Chen, Gang
2016-08-15
Here, we aimed to study the role and underlying mechanism of mTOR in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Experiment 1, the time course of mTOR activation in the cortex following SAH. Experiment 2, the role of mTOR in SAH-induced EBI. Adult SD rats were divided into four groups: sham group (n=18), SAH+vehicle group (n=18), SAH+rapamycin group (n=18), SAH+AZD8055 group (n=18). Experiment 3, we incubated enriched microglia with OxyHb. Rapamycin and AZD8055 were also used to demonstrate the mTOR's role on microglial polarization in vitro. The phosphorylation levels of mTOR and its substrates were significantly increased and peaked at 24h after SAH. Rapamycin or AZD8055 markedly decreased the phosphorylation levels of mTOR and its substrates and the activation of microglia in vivo, and promoted the microglial polarization from M1 phenotype to M2 phenotype. In addition, administration of rapamycin and AZD8055 following SAH significantly ameliorated EBI, including neuronal apoptosis, neuronal necrosis, brain edema and blood-brain barrier permeability. Our findings suggested that the rapamycin and AZD8055 could attenuate the development of EBI in this SAH model, possibly through inhibiting the activation of microglia by mTOR pathway. Copyright © 2016 Elsevier B.V. All rights reserved.
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Nonlinear analysis of saccade speed fluctuations during combined action and perception tasks
Stan, C.; Astefanoaei, C.; Pretegiani, E.; Optican, L.; Creanga, D.; Rufa, A.; Cristescu, C.P.
2014-01-01
Background: Saccades are rapid eye movements used to gather information about a scene which requires both action and perception. These are usually studied separately, so that how perception influences action is not well understood. In a dual task, where the subject looks at a target and reports a decision, subtle changes in the saccades might be caused by action-perception interactions. Studying saccades might provide insight into how brain pathways for action and for perception interact. New method: We applied two complementary methods, multifractal detrended fluctuation analysis and Lempel-Ziv complexity index to eye peak speed recorded in two experiments, a pure action task and a combined action-perception task. Results: Multifractality strength is significantly different in the two experiments, showing smaller values for dual decision task saccades compared to simple-task saccades. The normalized Lempel-Ziv complexity index behaves similarly i.e. is significantly smaller in the decision saccade task than in the simple task. Comparison with existing methods: Compared to the usual statistical and linear approaches, these analyses emphasize the character of the dynamics involved in the fluctuations and offer a sensitive tool for quantitative evaluation of the multifractal features and of the complexity measure in the saccades peak speeds when different brain circuits are involved. Conclusion: Our results prove that the peak speed fluctuations have multifractal characteristics with lower magnitude for the multifractality strength and for the complexity index when two neural pathways are simultaneously activated, demonstrating the nonlinear interaction in the brain pathways for action and perception. PMID:24854830
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Neuronal synchronization and selective color processing in the human brain.
Müller, Matthias M; Keil, Andreas
2004-04-01
In the present study, subjects selectively attended to the color of checkerboards in a feature-based attention paradigm. Induced gamma band responses (GBRs), the induced alpha band, and the event-related potential (ERP) were analyzed to uncover neuronal dynamics during selective feature processing. Replicating previous ERP findings, the selection negativity (SN) with a latency of about 160 msec was extracted. Furthermore, and similarly to previous EEG studies, a gamma band peak in a time window between 290 and 380 msec was found. This peak had its major energy in the 55- to 70-Hz range and was significantly larger for the attended color. Contrary to previous human induced gamma band studies, a much earlier 40- to 50-Hz peak in a time window between 160 and 220 msec after stimulus onset and, thus, concurrently to the SN was prominent with significantly more energy for attended as opposed to unattended color. The induced alpha band (9.8-11.7 Hz), on the other hand, exhibited a marked suppression for attended color in a time window between 450 and 600 msec after stimulus onset. A comparison of the time course of the 40- to 50-Hz and 55- to 70-Hz induced GBR, the induced alpha band, and the ERP revealed temporal coincidences for changes in the morphology of these brain responses. Despite these similarities in the time domain, the cortical source configuration was found to discriminate between induced GBRs and the SN. Our results suggest that large-scale synchronous high-frequency brain activity as measured in the human GBR play a specific role in attentive processing of stimulus features.
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The teen brain: insights from neuroimaging.
Giedd, Jay N
2008-04-01
Few parents of a teenager are surprised to hear that the brain of a 16-year-old is different from the brain of an 8-year-old. Yet to pin down these differences in a rigorous scientific way has been elusive. Magnetic resonance imaging, with the capacity to provide exquisitely accurate quantifications of brain anatomy and physiology without the use of ionizing radiation, has launched a new era of adolescent neuroscience. Longitudinal studies of subjects from ages 3-30 years demonstrate a general pattern of childhood peaks of gray matter followed by adolescent declines, functional and structural increases in connectivity and integrative processing, and a changing balance between limbic/subcortical and frontal lobe functions, extending well into young adulthood. Although overinterpretation and premature application of neuroimaging findings for diagnostic purposes remains a risk, converging data from multiple imaging modalities is beginning to elucidate the implications of these brain changes on cognition, emotion, and behavior.
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NASA Astrophysics Data System (ADS)
Khan, Mohammad Khurram
The Monte-Carlo based simulation environment for radiation therapy (SERA) software is used to simulate the dose administered to a patient undergoing boron neutron capture therapy (BNCT). Point sampling of tumor tissue results in an estimate of a uniform boron concentration scaling factor of 3.5. Under conventional treatment protocols, this factor is used to scale the boron component of the dose linearly and homogenously within the tumor and target volumes. The average dose to the tumor cells by such a method could be improved by better methods of quantifying the in-vivo 10B biodistribution. A better method includes radiolabeling para-Boronophenylalanine (p-BPA) with 18F and imaging the pharmaceutical using positron emission tomography (PET). This biodistribution of 18F-BPA can then be used to better predict the average dose delivered to the tumor regions. This work uses registered 18F-BPA PET images to incorporate the in-vivo boron biodistribution within current treatment planning. The registered 18F-BPA PET images are then coupled in a new computer software, PET2MRI.m, to linearly scale the boron component of the dose. A qualititative and quantitative assessment of the dose contours is presented using the two approaches. Tumor volume, tumor axial extent, and target locations are compared between using MRI or PET images to define the tumor volume. In addition, peak-to-normal brain value at tumor axial center is determined for pre and post surgery patients using 18F-BPA PET images. The differences noted between the registered GBM tumor volumes (range: 34.04--136.36%), tumor axial extent (range: 20--150%), and the beam target location (1.27--4.29 cm) are significantly different. The peak-to-normal brain values are also determined at the tumor axial center using the 18F-BPA PET images. The peak-to-normal brain values using the last frame of the pre-surgery study for the GBM patients ranged from 2.05--3.4. For post surgery time weighted PET data, the peak-to-normal brain value in the residual parts of the tumor ranged from 1.5--1.7. Qualitatively, boron dose contours are greatly shifted using PET images when compared with MRI images. Collectively, these differences can lead to significant reorientation of the beam and can significantly impact current BNCT treatment planning.
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Hatching the Cleidoic Egg: The Role of Thyroid Hormones
De Groef, Bert; Grommen, Sylvia V.H.; Darras, Veerle M.
2013-01-01
A major life stage transition in birds and other oviparous sauropsids is the hatching of the cleidoic egg. Not unlike amphibian metamorphosis, hatching in these species can be regarded as a transition from a relatively well-protected “aqueous” environment to a more hazardous and terrestrial life outside the egg, a transition in which thyroid hormones (THs) (often in concert with glucocorticoids) play an important role. In precocial birds such as the chicken, the perihatch period is characterized by peak values of THs. THs are implicated in the control of muscle development, lung maturation and the switch from chorioallantoic to pulmonary respiration, yolk sac retraction, gut development and induction of hepatic genes to accommodate the change in dietary energy source, initiation of thermoregulation, and the final stages of brain maturation as well as early post-hatch imprinting behavior. There is evidence that, at least for some of these processes, THs may have similar roles in non-avian sauropsids. In altricial birds such as passerines on the other hand, THs do not rise significantly until well after hatching and peak values coincide with the development of endothermy. It is not known how hatching-associated processes are regulated by hormones in these animals or how this developmental mode evolved from TH-dependent precocial hatching. PMID:23755041
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NASA Astrophysics Data System (ADS)
Cross, Nathan; Varghai, Davood; Flask, Chris A.; Feyes, Denise K.; Oleinick, Nancy L.; Dean, David
2009-02-01
This study aims to determine the effect of varying gadopentetate dimeglumine (Gd-DTPA) dose on Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) tracking of brain tumor photodynamic therapy (PDT) outcome. Methods: We injected 2.5 x 105 U87 cells (derived from human malignant glioma) into the brains of six athymic nude rats. After 9, 12, and 13 days DCE-MRI images were acquired on a 9.4 T micro-MRI scanner before and after administration of 100, 150, or 200 μL of Gd-DTPA. Results: Tumor region normalized DCE-MRI scan enhancement at peak was: 1.217 over baseline (0.018 Standard Error [SE]) at the 100 μL dose, 1.339 (0.013 SE) at the 150 μL dose, and 1.287 (0.014 SE) at the 200 μL dose. DCE-MRI peak tumor enhancement at the 150 μL dose was significantly greater than both the 100 μL dose (p < 3.323E-08) and 200 μL dose (p < 0.0007396). Discussion: In this preliminary study, the 150 μL Gd-DTPA dose provided the greatest T1 weighted contrast enhancement, while minimizing negative T2* effects, in DCE-MRI scans of U87-derived tumors. Maximizing Gd-DTPA enhancement in DCE-MRI scans may assist development of a clinically robust (i.e., unambiguous) technique for PDT outcome assessment.
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Scalzo, Fabien; Alger, Jeffry R; Hu, Xiao; Saver, Jeffrey L; Dani, Krishna A; Muir, Keith W; Demchuk, Andrew M; Coutts, Shelagh B; Luby, Marie; Warach, Steven; Liebeskind, David S
2013-07-01
Permeability images derived from magnetic resonance (MR) perfusion images are sensitive to blood-brain barrier derangement of the brain tissue and have been shown to correlate with subsequent development of hemorrhagic transformation (HT) in acute ischemic stroke. This paper presents a multi-center retrospective study that evaluates the predictive power in terms of HT of six permeability MRI measures including contrast slope (CS), final contrast (FC), maximum peak bolus concentration (MPB), peak bolus area (PB), relative recirculation (rR), and percentage recovery (%R). Dynamic T2*-weighted perfusion MR images were collected from 263 acute ischemic stroke patients from four medical centers. An essential aspect of this study is to exploit a classifier-based framework to automatically identify predictive patterns in the overall intensity distribution of the permeability maps. The model is based on normalized intensity histograms that are used as input features to the predictive model. Linear and nonlinear predictive models are evaluated using a cross-validation to measure generalization power on new patients and a comparative analysis is provided for the different types of parameters. Results demonstrate that perfusion imaging in acute ischemic stroke can predict HT with an average accuracy of more than 85% using a predictive model based on a nonlinear regression model. Results also indicate that the permeability feature based on the percentage of recovery performs significantly better than the other features. This novel model may be used to refine treatment decisions in acute stroke. Copyright © 2013 Elsevier Inc. All rights reserved.
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Effects of deferoxamine on blood-brain barrier disruption after subarachnoid hemorrhage.
Li, Yanjiang; Yang, Heng; Ni, Wei; Gu, Yuxiang
2017-01-01
Blood brain barrier (BBB) disruption is a key mechanism of subarachnoid hemorrhage (SAH)-induced brain injury. This study examined the mechanism of iron-induced BBB disruption after SAH and investigated the potential therapeutic effect of iron chelation on SAH. Male adult Sprague-Dawley rats had an endovascular perforation of left internal carotid artery bifurcation or sham operation. The rats were treated with deferoxamine (DFX) or vehicle (100mg/kg) for a maximum of 7 days. Brain edema, BBB leakage, behavioral and cognitive impairment were examined. In SAH rat, the peak time of brain edema and BBB impairment in the cortex was at day 3 after SAH. SAH resulted in a significant increase in ferritin expression in the cortex. The ferritin positive cells were colocalized with endothelial cells, pericytes, astrocytes, microglia and neurons. Compared with vehicle, DFX caused less ferritin upregulation, brain water content, BBB impairment, behavioral and cognitive deficits in SAH rats. The results suggest iron overload could be a therapeutic target for SAH induced BBB damage.
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Towards deep brain monitoring with superficial EEG sensors plus neuromodulatory focused ultrasound
Darvas, F; Mehić, E; Caler, CJ; Ojemann, JG; Mourad, PD
2017-01-01
Noninvasive recordings of electrophysiological activity have limited anatomical specificity and depth. We hypothesized that spatially tagging a small volume of brain with a unique electroencephalogram (EEG) signal induced by pulsed focused ultrasound (pFU) could overcome those limitations. As a first step towards testing this hypothesis, we applied transcranial ultrasound (2 MHz, 200 microsecond-long pulses applied at 1050 Hz for one second at a spatial peak temporal average intensity of 1.4 W/cm2) to the brains of anesthetized rats while simultaneously recording EEG signals. We observed a significant 1050 Hz electrophysiological signal only when ultrasound was applied to living brain. Moreover, amplitude demodulation of the EEG signal at 1050 Hz yielded measurement of gamma band (>30 Hz) brain activity consistent with direct measurements of that activity. These results represent preliminary support for use of pFU as a spatial tagging mechanism for non-invasive EEG-based mapping of deep brain activity with high spatial resolution. PMID:27181686
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Individual diversity of functional brain network economy.
Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Ganger, Sebastian; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert
2015-04-01
On average, brain network economy represents a trade-off between communication efficiency, robustness, and connection cost, although an analogous understanding on an individual level is largely missing. Evaluating resting-state networks of 42 healthy participants with seven Tesla functional magnetic resonance imaging and graph theory revealed that not even half of all possible connections were common across subjects. The strongest similarities among individuals were observed for interhemispheric and/or short-range connections, which may relate to the essential feature of the human brain to develop specialized systems within each hemisphere. Despite this marked variability in individual network architecture, all subjects exhibited equal small-world properties. Furthermore, interdependency between four major network economy metrics was observed across healthy individuals. The characteristic path length was associated with the clustering coefficient (peak correlation r=0.93), the response to network attacks (r=-0.97), and the physical connection cost in three-dimensional space (r=-0.62). On the other hand, clustering was negatively related to attack response (r=-0.75) and connection cost (r=-0.59). Finally, increased connection cost was associated with better response to attacks (r=0.65). This indicates that functional brain networks with high global information transfer also exhibit strong network resilience. However, it seems that these advantages come at the cost of decreased local communication efficiency and increased physical connection cost. Except for wiring length, the results were replicated on a subsample at three Tesla (n=20). These findings highlight the finely tuned interrelationships between different parameters of brain network economy. Moreover, the understanding of the individual diversity of functional brain network economy may provide further insights in the vulnerability to mental and neurological disorders.
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Yang, Lijun; Kress, Benjamin T; Weber, Harris J; Thiyagarajan, Meenakshisundaram; Wang, Baozhi; Deane, Rashid; Benveniste, Helene; Iliff, Jeffrey J; Nedergaard, Maiken
2013-05-01
Neurodegenerative diseases such as Alzheimer's are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30-180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans.
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2013-01-01
Background Neurodegenerative diseases such as Alzheimer’s are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. Methods Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30–180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. Results Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. Conclusion Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans. PMID:23635358
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32-channel 3 Tesla receive-only phased-array head coil with soccer-ball element geometry.
Wiggins, G C; Triantafyllou, C; Potthast, A; Reykowski, A; Nittka, M; Wald, L L
2006-07-01
A 32-channel 3T receive-only phased-array head coil was developed for human brain imaging. The helmet-shaped array was designed to closely fit the head with individual overlapping circular elements arranged in patterns of hexagonal and pentagonal symmetry similar to that of a soccer ball. The signal-to-noise ratio (SNR) and noise amplification (g-factor) in accelerated imaging applications were quantitatively evaluated in phantom and human images and compared with commercially available head coils. The 32-channel coil showed SNR gains of up to 3.5-fold in the cortex and 1.4-fold in the corpus callosum compared to a (larger) commercial eight-channel head coil. The experimentally measured g-factor performance of the helmet array showed significant improvement compared to the eight-channel array (peak g-factor 59% and 26% of the eight-channel values for four- and fivefold acceleration). The performance of the arrays is demonstrated in high-resolution and highly accelerated brain images. Copyright (c) 2006 Wiley-Liss, Inc.
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Lindberg, Olle R.; Brederlau, Anke; Kuhn, H. Georg
2014-01-01
Summary One of the major components of the subventricular zone (SVZ) neurogenic niche is the specialized vasculature. The SVZ vasculature is thought to be important in regulating progenitor cell proliferation and migration. Epidermal growth factor (EGF) is a mitogen with a wide range of effects. When stem and progenitor cells in the rat SVZ are treated with EGF, using intracerebroventricular infusion, dysplastic polyps are formed. Upon extended infusion, blood vessels are recruited into the polyps. In the current study we demonstrate how polyps develop through distinct stages leading up to angiogenesis. As polyps progress, microglia/macrophages accumulate in the polyp core concurrent with increasing cell death. Both microglia/macrophage accumulation and cell death peak during angiogenesis and subsequently decline following polyp vascularization. This model of inducible angiogenesis in the SVZ neurogenic niche suggests involvement of microglia/macrophages in acquired angiogenesis and can be used in detail to study angiogenesis in the adult brain. PMID:24749069
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Novel laser tissue-soldering technique for dural reconstruction.
Gil, Ziv; Shaham, Amit; Vasilyev, Tamar; Brosh, Tamar; Forer, Boaz; Katzir, Abraham; Fliss, Dan M
2005-07-01
The goal of this study was to use a modified version of the CO2 laser-soldering system to develop a simple and reliable technique for the repair of dural defects after excision of brain tumors. The authors used a CO2 fiber optic laser system that they had developed for heating, monitoring, and controlling tissue temperature in situ and in real time, thereby reducing damage to the brain parenchyma. They adapted the system for dural closure by using free fascial grafts in a porcine model. Measures for estimation of reconstruction quality included visual assessment under magnification and direct measurements of adhesive strength and cerebrospinal fluid leak (CSF) pressure. Reliable soldering was achieved in 54 of 57 experiments, providing a 95% success rate. The average peak adhesive strength was 82 +/- 3 mN/cm2. The measured leak pressure of the fascia-dura mater bond was 66 +/- 5 mm Hg. Conventional suturing performed using Prolene stitches resulted in immediate CSF leakage from areas between the stitches and from the area of the needle hole itself. Fascia-dura mater soldering using the CO2 laser is feasible and may support CSF pressure up to six times higher than normal intracranial pressure. Findings of this study may provide a basis for the development of new tools for dural reconstruction.
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Simulation of blast-induced early-time intracranial wave physics leading to traumatic brain injury.
Taylor, Paul A; Ford, Corey C
2009-06-01
The objective of this modeling and simulation study was to establish the role of stress wave interactions in the genesis of traumatic brain injury (TBI) from exposure to explosive blast. A high resolution (1 mm3 voxels) five material model of the human head was created by segmentation of color cryosections from the Visible Human Female data set. Tissue material properties were assigned from literature values. The model was inserted into the shock physics wave code, CTH, and subjected to a simulated blast wave of 1.3 MPa (13 bars) peak pressure from anterior, posterior, and lateral directions. Three-dimensional plots of maximum pressure, volumetric tension, and deviatoric (shear) stress demonstrated significant differences related to the incident blast geometry. In particular, the calculations revealed focal brain regions of elevated pressure and deviatoric stress within the first 2 ms of blast exposure. Calculated maximum levels of 15 KPa deviatoric, 3.3 MPa pressure, and 0.8 MPa volumetric tension were observed before the onset of significant head accelerations. Over a 2 ms time course, the head model moved only 1 mm in response to the blast loading. Doubling the blast strength changed the resulting intracranial stress magnitudes but not their distribution. We conclude that stress localization, due to early-time wave interactions, may contribute to the development of multifocal axonal injury underlying TBI. We propose that a contribution to traumatic brain injury from blast exposure, and most likely blunt impact, can occur on a time scale shorter than previous model predictions and before the onset of linear or rotational accelerations traditionally associated with the development of TBI.
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Astrocyte glycogen and lactate: New insights into learning and memory mechanisms.
Alberini, Cristina M; Cruz, Emmanuel; Descalzi, Giannina; Bessières, Benjamin; Gao, Virginia
2018-06-01
Memory, the ability to retain learned information, is necessary for survival. Thus far, molecular and cellular investigations of memory formation and storage have mainly focused on neuronal mechanisms. In addition to neurons, however, the brain comprises other types of cells and systems, including glia and vasculature. Accordingly, recent experimental work has begun to ask questions about the roles of non-neuronal cells in memory formation. These studies provide evidence that all types of glial cells (astrocytes, oligodendrocytes, and microglia) make important contributions to the processing of encoded information and storing memories. In this review, we summarize and discuss recent findings on the critical role of astrocytes as providers of energy for the long-lasting neuronal changes that are necessary for long-term memory formation. We focus on three main findings: first, the role of glucose metabolism and the learning- and activity-dependent metabolic coupling between astrocytes and neurons in the service of long-term memory formation; second, the role of astrocytic glucose metabolism in arousal, a state that contributes to the formation of very long-lasting and detailed memories; and finally, in light of the high energy demands of the brain during early development, we will discuss the possible role of astrocytic and neuronal glucose metabolisms in the formation of early-life memories. We conclude by proposing future directions and discussing the implications of these findings for brain health and disease. Astrocyte glycogenolysis and lactate play a critical role in memory formation. Emotionally salient experiences form strong memories by recruiting astrocytic β2 adrenergic receptors and astrocyte-generated lactate. Glycogenolysis and astrocyte-neuron metabolic coupling may also play critical roles in memory formation during development, when the energy requirements of brain metabolism are at their peak. © 2017 Wiley Periodicals, Inc.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ford, Corey C.; Taylor, Paul Allen
The objective of this modeling and simulation study was to establish the role of stress wave interactions in the genesis of traumatic brain injury (TBI) from exposure to explosive blast. A high resolution (1 mm{sup 3} voxels), 5 material model of the human head was created by segmentation of color cryosections from the Visible Human Female dataset. Tissue material properties were assigned from literature values. The model was inserted into the shock physics wave code, CTH, and subjected to a simulated blast wave of 1.3 MPa (13 bars) peak pressure from anterior, posterior and lateral directions. Three dimensional plots ofmore » maximum pressure, volumetric tension, and deviatoric (shear) stress demonstrated significant differences related to the incident blast geometry. In particular, the calculations revealed focal brain regions of elevated pressure and deviatoric (shear) stress within the first 2 milliseconds of blast exposure. Calculated maximum levels of 15 KPa deviatoric, 3.3 MPa pressure, and 0.8 MPa volumetric tension were observed before the onset of significant head accelerations. Over a 2 msec time course, the head model moved only 1 mm in response to the blast loading. Doubling the blast strength changed the resulting intracranial stress magnitudes but not their distribution. We conclude that stress localization, due to early time wave interactions, may contribute to the development of multifocal axonal injury underlying TBI. We propose that a contribution to traumatic brain injury from blast exposure, and most likely blunt impact, can occur on a time scale shorter than previous model predictions and before the onset of linear or rotational accelerations traditionally associated with the development of TBI.« less
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Sheu, Wayne H-H; Chuang, Hsiu-Chun; Cheng, Shiu-Min; Lee, Maw-Rong; Chou, Chi-Chi; Cheng, Fu-Chou
2011-03-25
Rosiglitazone is a potent synthetic peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist which improves glucose control in the plasma and reduces ischemic brain injury. However, the pharmacokinetics of rosiglitazone in the brain is still unclear. In this study, a method using liquid chromatography-mass spectrometry coupled with microdialysis and an auto-blood sampling system was developed to determine rosiglitazone and glucose concentration in the brain and blood of gerbils subjected to treatment with rosiglitazone (3.0 mg kg(-1), i.p.). The results showed the limit of detection was 0.04 μg L(-1) and the correlation coefficient was 0.9997 for the determination of rosiglitazone in the brain. The mean parameters, maximum drug concentration (C(max)) and the area under the concentration-time curve from time zero to time infinity (AUC(inf)), following rosiglitazone administration were 1.06±0.28 μg L(-1) and 296.82±44.67 μg min L(-1), respectively. The time to peak concentration (C(max) or T(max)) of rosiglitazone occurred at 105±17.10 min, and the mean elimination half-life (t(1/2)) from brain was 190.81±85.18 min after administration of rosiglitazone. The brain glucose levels decreased to 71% of the basal levels in the rosiglitazone-treated group when compared with those in the control (p<0.01). Treatment with rosiglitazone decreased blood glucose levels to 80% at 1h after pretreatment of rosiglitazone (p<0.05). In addition, pretreatment with rosiglitazone significantly reduced the cerebral infarct volume compared with that of the control group. These findings suggest that this method may be useful for simultaneous and continuous determination of rosiglitazone and glucose concentrations in brain and plasma. Rosiglitazone was effective at penetrating the blood-brain barrier as evidenced by the rapid appearance of rosiglitazone in the brain, and rosiglitazone may contribute to a reduction in the extent of injuries related to cerebral ischemic stroke via its hypoglycemic effect. Copyright © 2010 Elsevier B.V. All rights reserved.
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Fortuna, Ana; Alves, Gilberto; Soares-da-Silva, Patrício; Falcão, Amílcar
2013-11-01
In silico approaches to predict absorption, distribution, metabolism and excretion (ADME) of new drug candidates are gaining a relevant importance in drug discovery programmes. When considering particularly the pharmacokinetics during the development of oral antiepileptic drugs (AEDs), one of the most prominent goals is designing compounds with good bioavailability and brain penetration. Thus, it is expected that in silico models able to predict these features may be applied during the early stages of AEDs discovery. The present investigation was mainly carried out in order to generate in vivo pharmacokinetic data that can be utilized for development and validation of in silico models. For this purpose, a single dose of each compound (1.4mmol/kg) was orally administered to male CD-1 mice. After quantifying the parent compound and main metabolites in plasma and brain up to 12h post-dosing, a non-compartmental pharmacokinetic analysis was performed and the corresponding brain/plasma ratios were calculated. Moreover the plasma protein binding was estimated in vitro applying the ultrafiltration procedure. The present in vivo pharmacokinetic characterization of the test compounds and corresponding metabolites demonstrated that the metabolism extensively compromised the in vivo activity of CBZ derivatives and their toxicity. Furthermore, it was clearly evidenced that the time to reach maximum peak concentration, bioavailability (given by the area under the curve) and metabolic stability (given by the AUC0-12h ratio of the parent compound and total systemic drug) influenced the in vivo pharmacological activities and must be considered as primary parameters to be investigated. All the test compounds presented brain/plasma ratios lower than 1.0, suggesting that the blood-brain barrier restricts drug entry into the brain. In agreement with in vitro studies already performed within our research group, CBZ, CBZ-10,11-epoxide and oxcarbazepine exhibited the highest brain/plasma ratios (>0.50), followed by eslicarbazepine, R-licarbazepine, trans-diol and BIA 2-024 (ratios within 0.05-0.50). BIA 2-265 was not found in the biophase, probably due to its high plasma-protein bound fraction (>90%) herein revealed for the first time. The comparative in vivo pharmacokinetic data obtained in the present work might be usefully applied in the context of discovery of new antiepileptic drugs that are derivatives of CBZ. Copyright © 2013 Elsevier B.V. All rights reserved.
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Tsuji, Ryozo; Fattori, Vittorio; Abe, Shin-ichi; Costa, Lucio G; Kobayashi, Kumiko
2008-01-01
Exposure to ethanol during development induces severe brain damage resulting in a number of CNS dysfunctions including microencephaly and mental retardation in humans and in laboratory animals. The most vulnerable period to ethanol neurotoxicity coincides with the peak of brain growth spurt. Recently, neurotrophic factors and/or their signal transduction pathways have been reported as a potential relevant target for the developmental neurotoxicity of ethanol. The present studies were designed to investigate the effects of ethanol given in various developmental phases during the brain growth spurt in rats. Rat pups were assigned to the three treatment groups and treated with 5 g/kg of ethanol for three days, on postnatal days (PND) 2-4, 6-8 or 13-15. Whole brain weights were reduced only in the PND 6-8 group concurrently with the reduction of GDNF mRNA in cortex in this group. BDNF mRNA expression was reduced in both the PND 6-8 and 13-15 groups, while mRNA expressions of NT-3 and NGF were unchanged in all three groups. Phospho-Akt level was mostly reduced in the PND 6-8 group. Both phospho-MAPK and p-70S6 kinase levels were decreased in all groups whereas no changes were observed in either phospho-PKCzeta or CREB level. The phosphorylation of Akt was immediately inhibited after single administration of ethanol, and its inhibition was correlated with variations in blood ethanol concentration. These findings suggest that GDNF and the phosphorylation of Akt play a possible key role in the ethanol-induced developmental neurotoxicity.
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NASA Astrophysics Data System (ADS)
Fuller, M.; Zinin, P.; Favia, J.; Tatsumi, L.; Kletetschka, G.; Adachi, T.
2007-12-01
Increases of iron in the human brain with age have been observed and may be accompanied by the development of neurodegenerative diseases, such as Alzheimer's. We have measured the magnetic characteristics of several sets of slides of hippocampal tissue from deceased Alzheimer patients. The slides were made available by the Harvard Brain Bank. The pathology of the tissue was classified in the Braak stages I to VI used to describe the progression of the disease. In general, the slides from patients with higher Braak stages and development of fibrillary tangles and plaques had greater magnetic moments than did those with Braak stage II. However, the peak values were at stage IV and V. To mitigate errors due to the inevitable differences in masses of the tissue on individual slides and their precise location in the hippocampus, ratios of magnetic properties were also observed. Ratios of Anhysteretic Remanent Magnetizaton (ARM) to Isothermal Remanent Magnetization (IRM) were obtained and showed a decrease from Stage II to the more advanced stages, with the minimum values at stages IV and V. The acquisition and demagnetization of IRM are consistent with the presence of magnetite, but also indicate a magnetically harder phase.
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Narang, Nikhil; Armstead, Sumiko I; Stream, Amanda; Abdullah, Shuaib M; See, Raphael; Snell, Peter G; McGavock, Jonathan; Ayers, Colby R; Gore, M Odette; Khera, Amit; de Lemos, James A; McGuire, Darren K
2011-04-01
Thiazolidinediones cause peripheral oedema, the aetiology of which remains poorly understood. In a sub-study of a 6-month trial comparing rosiglitazone (Rsg) versus placebo, we compared those with versus without oedema among the 74 subjects treated with Rsg with respect to peak oxygen consumption indexed to fat-free mass (VO(2peak-FFM) ), cardiac MRI and markers of plasma volume expansion. Almost half (49%) of the Rsg-treated patients developed oedema. Baseline VO(2peak-FFM) was not different between those with versus without oedema (25.8 versus 28.2 ml/kg/min; p = 0.22) and declined 5% in the oedema group (Δ -1.3 ml/min/kg; p = 0.005) with no change in those without oedema. Stroke volume increased in both groups (Δ 8.7 and 8.8 ml; p < 0.001 for each); end-diastolic volume increased only in those with oedema (+13.1 ml; p = 0.001). No other cardiac function changes were observed. In both groups, weight increased (3.6 and 2.2 kg) and haematocrit decreased (-3.2% and -2.1%; p < 0.001 for each). In those with oedema, albumin decreased (-0.2 g/dl) and brain natriuretic peptide increased (11.9 pg/ml; p < 0.03 for each). Oedema was associated with a small decline in VO(2peak FFM), no adverse effects on cardiac function, and changes in selected measures suggesting that volume expansion underpins Rsg oedema.
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Comparing CT perfusion with oxygen partial pressure in a rabbit VX2 soft-tissue tumor model.
Sun, Chang-Jin; Li, Chao; Lv, Hai-Bo; Zhao, Cong; Yu, Jin-Ming; Wang, Guang-Hui; Luo, Yun-Xiu; Li, Yan; Xiao, Mingyong; Yin, Jun; Lang, Jin-Yi
2014-01-01
The aim of this study was to evaluate the oxygen partial pressure of the rabbit model of the VX2 tumor using a 64-slice perfusion CT and to compare the results with that obtained using the oxygen microelectrode method. Perfusion CT was performed for 45 successfully constructed rabbit models of a VX2 brain tumor. The perfusion values of the brain tumor region of interest, the blood volume (BV), the time to peak (TTP) and the peak enhancement intensity (PEI) were measured. The results were compared with the partial pressure of oxygen (PO2) of that region of interest obtained using the oxygen microelectrode method. The perfusion values of the brain tumor region of interest in 45 successfully constructed rabbit models of a VX2 brain tumor ranged from 1.3-127.0 (average, 21.1 ± 26.7 ml/min/ml); BV ranged from 1.2-53.5 ml/100g (average, 22.2 ± 13.7 ml/100g); PEI ranged from 8.7-124.6 HU (average, 43.5 ± 28.7 HU); and TTP ranged from 8.2-62.3 s (average, 38.8 ± 14.8 s). The PO2 in the corresponding region ranged from 0.14-47 mmHg (average, 16 ± 14.8 mmHg). The perfusion CT positively correlated with the tumor PO2, which can be used for evaluating the tumor hypoxia in clinical practice.
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Energy harvesting from arterial blood pressure for powering embedded micro sensors in human brain
NASA Astrophysics Data System (ADS)
Nanda, Aditya; Karami, M. Amin
2017-03-01
This manuscript investigates energy harvesting from arterial blood pressure via the piezoelectric effect for the purpose of powering embedded micro-sensors in the human brain. One of the major hurdles in recording and measuring electrical data in the human nervous system is the lack of implantable and long term interfaces that record neural activity for extended periods of time. Recently, some authors have proposed micro sensors implanted deep in the brain that measure local electrical and physiological data which are then communicated to an external interrogator. This paper proposes a way of powering such interfaces. The geometry of the proposed harvester consists of a piezoelectric, circular, curved bimorph that fits into the blood vessel (specifically, the Carotid artery) and undergoes bending motion because of blood pressure variation. In addition, the harvester thickness is constrained such that it does not modify arterial wall dynamics. This transforms the problem into a known strain problem and the integral form of Gauss's law is used to obtain an equation relating arterial wall motion to the induced voltage. The theoretical model is validated by means of a Multiphysics 3D-FEA simulation comparing the harvested power at different load resistances. The peak harvested power achieved for the Carotid artery (proximal to Brain), with PZT-5H, was 11.7 μW. The peak power for the Aorta was 203.4 μW. Further, the variation of harvested power with variation in the harvester width and thickness, arterial contractility, and pulse rate is investigated. Moreover, potential application of the harvester as a chronic, implantable and real-time Blood pressure sensor is considered. Energy harvested via this mechanism will also have applications in long-term, implantable Brain Micro-stimulation.
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NASA Astrophysics Data System (ADS)
Sawada, Kazuaki; Kawakami, Ryosuke; Fang, Yi-Cheng; Hung, Jui-Hung; Kozawa, Yuichi; Otomo, Kohei; Sato, Shunichi; Yokoyama, Hiroyuki; Nemoto, Tomomi
2018-02-01
In vivo two-photon microscopy is an advantageous technique for observing living mouse brains at high spatial resolutions. We previously used a 1064 nm high-power light source based on an electrically controllable gain-switched laser diode (maximum power: 4 W, repetition rate: 10 MHz, pulse width: 7.5 picoseconds) and successfully visualized EYFP expressing neurons at deeper regions in H-line mouse brains under living conditions. However, severe damages were frequently observed when the laser power after the objective lens was over 600 mW, suggesting that a higher average power might not be suitable for visualizing neural structures and functions at deep regions. To increase fluorescent signals as a strategy to avoid such invasions, here, we evaluated the effects of the excitation laser parameters such as the repetition rate (5 - 10 MHz), or the peak power, at the moderate average powers (10 - 500 mW), by taking the advantage that this electrically controllable light source could be used to change the repetition rate independently from the average power or the pulse width. The fluorescent signals of EYFP at layer V of the cerebral cortex were increased by approximately twofold when the repetition rate was decreased from 10 MHz to 5 MHz at the same average power. We also confirmed similar effects in the EYFP solution (335 μM) and fixed brain slices. These results suggest that in vivo two-photon microscopic imaging might be improved by increasing the peak power at the same average power while avoiding the severe damages in living brains.
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Wu, Xiaoping; Adriany, Gregor; Ugurbil, Kamil; Van de Moortele, Pierre-Francois
2013-01-01
Successful implementation of homogeneous slice-selective RF excitation in the human brain at 9.4T using 16-channel parallel transmission (pTX) is demonstrated. A novel three-step pulse design method incorporating fast real-time measurement of eddy current induced B0 variations as well as correction of resulting phase errors during excitation is described. To demonstrate the utility of the proposed method, phantom and in-vivo experiments targeting a uniform excitation in an axial slice were conducted using two-spoke pTX pulses. Even with the pre-emphasis activated, eddy current induced B0 variations with peak-to-peak values greater than 4 kHz were observed on our system during the rapid switches of slice selective gradients. This large B0 variation, when not corrected, resulted in drastically degraded excitation fidelity with the coefficient of variation (CV) of the flip angle calculated for the region of interest being large (∼12% in the phantom and ∼35% in the brain). By comparison, excitation fidelity was effectively restored, and satisfactory flip angle uniformity was achieved when using the proposed method, with the CV value reduced to ∼3% in the phantom and ∼8% in the brain. Additionally, experimental results were in good agreement with the numerical predictions obtained from Bloch simulations. Slice-selective flip angle homogenization in the human brain at 9.4T using 16-channel 3D spoke pTX pulses is achievable despite of large eddy current induced excitation phase errors; correcting for the latter was critical in this success. PMID:24205098
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NASA Astrophysics Data System (ADS)
Anand, Suresh; Cicchi, Riccardo; Giordano, Flavio; Conti, Valerio; Buccoliero, Anna Maria; Guerrini, Renzo; Pavone, Francesco S.
2017-02-01
Focal cortical dysplasia (FCD) is an abnormality in the cerebral cortex that is caused by malformations during cortical development. Currently, magnetic resonance imaging (MRI) and electro-corticography (ECoG) are used for detecting FCD. On the downside, MRI is very much insensitive to small malformations in the brain, while ECoG is an invasive and time consuming procedure. Recently, optical techniques were widely exploited as a minimally invasive and quantitative approaches for disease diagnosis. These techniques include fluorescence and Raman spectroscopy. The aim of this investigation is to study the diagnostic performances of optical spectroscopy incorporating fluorescence (at 378 nm and 445 nm excitation wavelengths) and Raman spectroscopy (at 785 nm excitation) for the discrimination of FCD from normal brain in pediatric subjects. The study included 10 normal and 17 FCD tissue sites from 3 normal and 7 FCD samples. The emission spectra of FCD at 378 nm excitation wavelength presented a blue-shifted peak with respect to normal tissue. Prominent spectral differences between normal and FCD tissue were observed at 1298 cm-1, 1302 cm-1, 1445 cm-1 and 1660 cm-1 using Raman spectroscopy. Tissue classification models were developed using a multivariate statistical method, principal component analysis. This study demonstrates that a combined spectroscopic approach can provide a better diagnostic capability for classifying normal and FCD tissues. Further, the implementation of the technology within a fiber probe could open the way for in vivo diagnostics and intra-operative surgical guidance.
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Distribution, pharmacokinetics and primary metabolism model of tramadol in zebrafish.
Zhuo, Huiqin; Jin, Hongwei; Peng, Huifang; Huang, Heqing
2016-12-01
The current study aimed to develop a rapid, robust and adequately sensitive method for simultaneous determination of the concentration of tramadol and its active metabolites in zebrafish. The pharmacokinetic and elimination pattern of tramadol and its major phase I metabolites following oral or intramuscular administration in zebrafish tissues was achieved using electrospray ionization‑quadrupole‑time of flight/mass spectrometry (ESI‑Q‑TOF/MS) and gas chromatography/mass spectrometry (GC‑MS). Following administration, the metabolisms were detected in the brain, eyes, muscle and gill tissues within 1 h. Two tramadol metabolites, O‑ and N‑desmethyltramadol, were detected in brain tissue, with N‑desmethyltramadol detected at a higher level. Following GC‑MS detection the curve indicated an initial rapid phase, corresponding to the detection of the tramadol within 1 min, and reached peak value in the brain at 5 min. Faster drug clearance was detected in low‑dose groups, and concentration had dropped around the to initial level (1.11 µg) at 20 min, but was detectable for up to 3 h. However, it took 80 min to fall back to the initial value (1.73 µg) in the high‑dose groups, and tramadol was detectable for up to 4 h. This study developed and validated a simple and high throughput analytical procedure to determine the distribution and pharmacokinetic profiles of tramadol, and its primary metabolites in tissues of zebrafish.
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Ryan, G.; Klein, D.; Knapp, E.; Hosie, M. J.; Grimes, T.; Mabruk, M. J. E. M. F.; Jarrett, O.; Callanan, J. J.
2003-01-01
Animal models of human immunodeficiency virus 1, such as feline immunodeficiency virus (FIV), provide the opportunities to dissect the mechanisms of early interactions of the virus with the central nervous system (CNS). The aims of the present study were to evaluate viral loads within CNS, cerebrospinal fluid (CSF), ocular fluid, and the plasma of cats in the first 23 weeks after intravenous inoculation with FIVGL8. Proviral loads were also determined within peripheral blood mononuclear cells (PBMCs) and brain tissue. In this acute phase of infection, virus entered the brain in the majority of animals. Virus distribution was initially in a random fashion, with more diffuse brain involvement as infection progressed. Virus in the CSF was predictive of brain parenchymal infection. While the peak of virus production in blood coincided with proliferation within brain, more sustained production appeared to continue in brain tissue. In contrast, proviral loads in the brain decreased to undetectable levels in the presence of a strengthening PBMC load. A final observation in this study was that there was no direct correlation between viral loads in regions of brain or ocular tissue and the presence of histopathology. PMID:12805447
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Lépée-Lorgeoux, I; Betancur, C; Rostène, W; Pélaprat, D
1999-03-12
The postnatal ontogeny of the levocabastine-sensitive neurotensin receptor (NT2) mRNA was studied by in situ hybridization in the rat brain and compared with the distribution of the levocabastine-insensitive NT1 receptor. NT2 receptor mRNA was absent at birth from all brain structures except the ependymal cell layer lining the ventricles. The development of NT2 receptor mRNA followed three ontogenetic patterns. The first pattern, involving the majority of the cerebral gray matter, was characterized by a continuous increase from postnatal day 5 (P5) to P30. The second one, involving regions rich in myelinated fibers such as the corpus callosum and lacunosum moleculare layer of the hippocampus, exhibited a pronounced increase between P5 and P10, peaked at P15 and was followed by a plateau or a slight decrease. The third pattern was observed in the ependymal cell layer lining the olfactory and lateral ventricles, where the high labeling already present at birth continued to increase during development. These different developmental patterns could reflect the variety of cells expressing NT2 receptor mRNA, including neurons, protoplasmic astrocytes in gray matter, fibrous astrocytes present in myelinated fibers tracts, and ependymal cells. In contrast, NT1 receptor mRNA, which seems to be associated only with neurons, was highly and transiently expressed during the perinatal period in the cerebral cortex, hippocampus and striatal neuroepithelium. Other regions, notably the ventral tegmental area and substantia nigra compacta, exhibited a gradual increase in NT1 receptor signal, reaching adult levels by P21. Both the differential localization and ontogenetic profiles of NT1 and NT2 receptor mRNAs suggest different involvement of these two receptors in brain functions and development. Copyright 1999 Elsevier Science B.V.
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Opsommer, E; Plaghki, L
2001-12-28
Possible maturational changes in the thermoalgesic system were studied by reaction times (RT) and late (Adelta-fibre) laser evoked potentials (LEPs) following CO(2) laser heat stimulation of the hand in healthy children (n=12) and young adults (n=12). In children (10+/-2 years) LEPs presented a negative-positive complex with maximum amplitude (peak-to-peak 71+/-35 microV) at the vertex and latencies of 248+/-82 and 433+/-104 ms, respectively. As compared to adults (24+/-3 years), children had a significant increased peak-to-peak amplitude (+25.7 microV; P=0.03) although no difference in latencies and topography. Median RT (710 ms) was also significantly increased (+312 ms; P<0.005) in children. A decrease in RT and late LEP amplitude from childhood to adulthood may reflect aspects of maturation in sensory processing of the thermoalgesic system.
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Auditory evoked magnetic fields to speech stimuli in newborns--effect of sleep stages.
Pihko, E; Sambeth, A; Leppänen, P H T; Okada, Y; Lauronen, L
2004-11-30
The aim of the study was to examine whether a newborn can detect changes in a speech stimulus consisting of a fricative followed by a vowel /su/. In addition, we studied possible effect of the two sleep stages (active and quiet sleep) on the evoked magnetic responses. In young children (6 years), the same stimulus evokes a prominent deflection, consisting of two peaks. The first one (P1m) is evoked by the beginning of the fricative consonant and has a latency of about 145 ms. The second peak (P2m) with a latency of 340 ms, is evoked by the switch to the vowel. In newborns (n = 10), the waveform resembled that of the older children but latencies of the corresponding peaks were longer, 190 and 435 ms, correspondingly. The results suggest that already the newborn brain detects the change inside the auditory speech stimulus, namely the fricative sound changing into a vowel. However, the immaturity of the brain is reflected in the prolonged latencies. In addition, the responses were higher in amplitude in quiet sleep than in active sleep (F (1.9) = 36.5; p < 0.0002). This is in line with the enhanced somatosensory magnetic fields to tactile stimulation in quiet compared to active sleep in newborns.
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The role of symmetry in neural networks and their Laplacian spectra.
de Lange, Siemon C; van den Heuvel, Martijn P; de Reus, Marcel A
2016-11-01
Human and animal nervous systems constitute complexly wired networks that form the infrastructure for neural processing and integration of information. The organization of these neural networks can be analyzed using the so-called Laplacian spectrum, providing a mathematical tool to produce systems-level network fingerprints. In this article, we examine a characteristic central peak in the spectrum of neural networks, including anatomical brain network maps of the mouse, cat and macaque, as well as anatomical and functional network maps of human brain connectivity. We link the occurrence of this central peak to the level of symmetry in neural networks, an intriguing aspect of network organization resulting from network elements that exhibit similar wiring patterns. Specifically, we propose a measure to capture the global level of symmetry of a network and show that, for both empirical networks and network models, the height of the main peak in the Laplacian spectrum is strongly related to node symmetry in the underlying network. Moreover, examination of spectra of duplication-based model networks shows that neural spectra are best approximated using a trade-off between duplication and diversification. Taken together, our results facilitate a better understanding of neural network spectra and the importance of symmetry in neural networks. Copyright © 2016 Elsevier Inc. All rights reserved.
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Kamisawa, Tomoko; Ikawa, Masamichi; Hamano, Tadanori; Nagata, Miwako; Kimura, Hirohiko; Yoneda, Makoto
2014-01-01
A 67-year-old man living alone was admitted for acute disturbance of consciousness during winter. He presented with semicoma, a decorticate posture, and exaggerated tendon reflexes of the limbs, but brainstem reflexes were intact. The carboxyhemoglobin (COHb) level was normal in arterial blood gas on admission, and protein in cerebrospinal fluid was increased without pleocytosis. Brain MRI showed diffuse T2 high intensities in the deep white matter bilaterally without a contrast effect and abnormal T1 intensity in the pallidum. (1)H-MR spectroscopy (MRS) of the white matter lesion demonstrated findings suggesting demyelination as an increased choline peak, enhanced anaerobic metabolism as increased lactate and lipids peaks, and reduced neurons as a decreased N-acetylaspartate peak, which corresponded to delayed encephalopathy due to the interval form of carbon monoxide (CO) poisoning. The possibility of CO exposure due to coal briquette use 2 weeks before the symptomatic onset was indicated by his family, so he was diagnosed with CO poisoning. His consciousness slightly improved with corticosteroid therapy and repetitive hyperbaric oxygen therapy, but brain MRI and MRS findings did not improve. Characteristic MRS findings of leukoencephalopathy are helpful for diagnosing the interval form of CO poisoning in the case of a normal COHb level.
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Different Brain Responses to Pain and Its Expectation in the Dental Chair.
Racek, A J; Hu, X; Nascimento, T D; Bender, M C; Khatib, L; Chiego, D; Holland, G R; Bauer, P; McDonald, N; Ellwood, R P; DaSilva, A F
2015-07-01
A dental appointment commonly prompts fear of a painful experience, yet we have never fully understood how our brains react to the expectation of imminent tooth pain once in a dental chair. In our study, 21 patients with hypersensitive teeth were tested using nonpainful and painful stimuli in a clinical setting. Subjects were tested in a dental chair using functional near-infrared spectroscopy to measure cortical activity during a stepwise cold stimulation of a hypersensitive tooth, as well as nonpainful control stimulation on the same tooth. Patients' sensory-discriminative and emotional-cognitive cortical regions were studied through the transition of a neutral to a painful stimulation. In the putative somatosensory cortex contralateral to the stimulus, 2 well-defined hemodynamic peaks were detected in the homuncular orofacial region: the first peak during the nonpainful phase and a second peak after the pain threshold was reached. Moreover, in the upper-left and lower-right prefrontal cortices, there was a significant active hemodynamic response in only the first phase, before the pain. Subsequently, the same prefrontal cortical areas deactivated after a painful experience had been reached. Our study indicates for the first time that pain perception and expectation elicit different hemodynamic cortical responses in a dental clinical setting. © International & American Associations for Dental Research 2015.
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Involvement of Cerebellum in Leigh Syndrome: Case Report and Review of the Literature.
Chourasia, Nitish; Adejumo, Rahmat B; Patel, Rajan P; Koenig, Mary Kay
2017-09-01
Leigh syndrome is an early-onset progressive neurodegenerative disorder typically involving lesions of the bilateral basal ganglia, thalami, and brainstem. Isolated involvement of the cerebellum is uncommon. We present a six-year-old boy with Leigh syndrome who presented with recurrent episodes of ataxia and dysarthria. He was diagnosed with Leigh syndrome at two years of age with bilateral basal ganglia lesions on brain magnetic resonance imaging (MRI). Genetic testing confirmed a diagnosis of Leigh syndrome secondary to a homoplasmic mitochondrial DNA mutation (m.9176T>C). He experienced regressive episodes (ages five and six years). Each regressive episode had a similar presentation with worsening of baseline ataxia and dysarthria. The first episode mimicked infectious cerebellitis, with elevated cerebral spinal fluid (CSF) protein and white blood cell count. No organisms were isolated from the CSF/blood during any of the regressive episodes. Brain MRI consistently showed cerebellar lesions, however cerebellar spectroscopy during the second episode found an elevated lactate peak, a decrease of the N-acetylaspartate peak, and elevation of the choline peak; consistent with an acute exacerbation of Leigh syndrome. Leigh syndrome can present primarily with involvement of the cerebellum, and it should be considered in the differential diagnosis for acute cerebellitis. Published by Elsevier Inc.
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Lee, Jae Eun; Kim, Bum Soo; Park, Wan; Huh, Jung Kwon; Kim, Byung Jin; Sung, Ki Chul; Kang, Jin Ho; Lee, Man Ho; Park, Jung Ro
2010-04-01
The correlation between brain natruretic peptide (BNP) level and cardiac autonomic function has been studied in type 2 diabetic patients. However, there is limited data from patients with normal systolic function. We evaluated the association between heart rate recovery (HRR) representing autonomic dysfunction and three plasma BNP levels: pre-exercise, post-exercise, and change during exercise in patients with normal systolic function. Subjects included 105 patients with chest pain and normal systolic function. HRR was defined as the difference between the peak heart rate and the rate measured two minutes after completion of a treadmill exercise test. We measured plasma BNP levels before exercise, 5 minutes after completion of exercise, and during exercise (absolute value of difference between pre- and post-exercise BNP levels). Patients with abnormal HRR values (
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Makeig, S; Westerfield, M; Jung, T P; Covington, J; Townsend, J; Sejnowski, T J; Courchesne, E
1999-04-01
Human event-related potentials (ERPs) were recorded from 10 subjects presented with visual target and nontarget stimuli at five screen locations and responding to targets presented at one of the locations. The late positive response complexes of 25-75 ERP average waveforms from the two task conditions were simultaneously analyzed with Independent Component Analysis, a new computational method for blindly separating linearly mixed signals. Three spatially fixed, temporally independent, behaviorally relevant, and physiologically plausible components were identified without reference to peaks in single-channel waveforms. A novel frontoparietal component (P3f) began at approximately 140 msec and peaked, in faster responders, at the onset of the motor command. The scalp distribution of P3f appeared consistent with brain regions activated during spatial orienting in functional imaging experiments. A longer-latency large component (P3b), positive over parietal cortex, was followed by a postmotor potential (Pmp) component that peaked 200 msec after the button press and reversed polarity near the central sulcus. A fourth component associated with a left frontocentral nontarget positivity (Pnt) was evoked primarily by target-like distractors presented in the attended location. When no distractors were presented, responses of five faster-responding subjects contained largest P3f and smallest Pmp components; when distractors were included, a Pmp component appeared only in responses of the five slower-responding subjects. Direct relationships between component amplitudes, latencies, and behavioral responses, plus similarities between component scalp distributions and regional activations reported in functional brain imaging experiments suggest that P3f, Pmp, and Pnt measure the time course and strength of functionally distinct brain processes.
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Fluorescence lifetime spectroscopy for guided therapy of brain tumors.
Butte, Pramod V; Mamelak, Adam N; Nuno, Miriam; Bannykh, Serguei I; Black, Keith L; Marcu, Laura
2011-01-01
This study evaluates the potential of time-resolved laser induced fluorescence spectroscopy (TR-LIFS) as intra-operative tool for the delineation of brain tumor from normal brain. Forty two patients undergoing glioma (WHO grade I-IV) surgery were enrolled in this study. A TR-LIFS prototype apparatus (gated detection, fast digitizer) was used to induce in-vivo fluorescence using a pulsed N2 laser (337 nm excitation, 0.7 ns pulse width) and to record the time-resolved spectrum (360-550 nm range, 10 nm interval). The sites of TR-LIFS measurement were validated by conventional histopathology (H&E staining). Parameters derived from the TR-LIFS data including intensity values and time-resolved intensity decay features (average fluorescence lifetime and Laguerre coefficients values) were used for tissue characterization and classification. 71 areas of tumor and normal brain were analyzed. Several parameters allowed for the differentiation of distinct tissue types. For example, normal cortex (N=35) and normal white matter (N=12) exhibit a longer-lasting fluorescence emission at 390 nm (τ390=2.12±0.10 ns) when compared with 460 nm (τ460=1.16±0.08 ns). High grade glioma (grades III and IV) samples (N=17) demonstrate emission peaks at 460 nm, with large variation at 390 nm while low grade glioma (I and II) samples (N=7) demonstrated a peak fluorescence emission at 460 nm. A linear discriminant algorithm allowed for the classification of low-grade gliomas with 100% sensitivity and 98% specificity. High-grade glioma demonstrated a high degree of heterogeneity thus reducing the discrimination accuracy of these tumors to 47% sensitivity and 94% specificity. Current findings demonstrate that TR-LIFS holds the potential to diagnose brain tumors intra-operatively and to provide a valuable tool for aiding the neurosurgeon-neuropathologist team in to rapidly distinguish between tumor and normal brain during surgery. Copyright © 2010 Elsevier Inc. All rights reserved.
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Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex
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 periods per 24 h recording episodes showed an early and a delayed peak on Day 7. Patients surviving subarachnoid haemorrhage with poor outcome at 6 months showed significantly higher total and peak numbers of spreading depolarizations and significantly longer total and peak depression periods during the electrocorticographic monitoring than patients with good outcome. In a semi-structured telephone interview 3 years after the initial haemorrhage, 44% of the subarachnoid haemorrhage survivors had developed late post-haemorrhagic seizures requiring anti-convulsant medication. In those patients, peak spreading depolarization number had been significantly higher [15.1 (11.4–30.8) versus 7.0 (0.8–11.2) events per day, P = 0.045]. In summary, monopolar recordings here provided unequivocal evidence of spreading convulsions in patients. Hence, practically all major pathological cortical network events in animals have now been observed in people. Early spreading depolarizations may indicate a risk for late post-haemorrhagic seizures. PMID:22120143
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Greenshaw, A J; Turrkish, S; Davis, B A
2002-01-01
The functional aversive stimulus properties of several IP doses of (+/-)-amphetamine (1.25-10 mg.kg-1), 2-phenylethylamine (PEA, 2.5-10 mg.kg-1, following inhibition of monoamine oxidase with pargyline 50 mg.kg-1) and phenylethanolamine (6.25-50 mg.kg-1) were measured with the conditioned taste aversion (CTA) paradigm. A two-bottle choice procedure was used, water vs. 0.1 % saccharin with one conditioning trial and three retention trials. (+/-)-Amphetamine and phenylethanolamine induced a significant conditioned taste aversion but PEA did not. (+/-)-Amphetamine and PEA increased spontaneous locomotor activity but phenylethanolamine had no effects on this measure. Measurement of whole brain levels of these drugs revealed that the peak brain elevation of PEA occurred at approximately 10 min whereas the peak elevations of (+/-)-amphetamine and phenylethanolamine occurred at approximately 20 min. The present failure of PEA to elicit conditioned taste aversion learning is consistent with previous reports for this compound. The differential functional aversive stimulus effects of these three compounds are surprising since they exhibit similar discriminative stimulus properties and both (+/-)-amphetamine and PEA are self-administered by laboratory animals. The present data suggest that time to maximal brain concentrations following peripheral injection may be a determinant of the aversive stimulus properties of PEA derivatives.
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Hybrid EEG-fNIRS-Based Eight-Command Decoding for BCI: Application to Quadcopter Control.
Khan, Muhammad Jawad; Hong, Keum-Shik
2017-01-01
In this paper, a hybrid electroencephalography-functional near-infrared spectroscopy (EEG-fNIRS) scheme to decode eight active brain commands from the frontal brain region for brain-computer interface is presented. A total of eight commands are decoded by fNIRS, as positioned on the prefrontal cortex, and by EEG, around the frontal, parietal, and visual cortices. Mental arithmetic, mental counting, mental rotation, and word formation tasks are decoded with fNIRS, in which the selected features for classification and command generation are the peak, minimum, and mean ΔHbO values within a 2-s moving window. In the case of EEG, two eyeblinks, three eyeblinks, and eye movement in the up/down and left/right directions are used for four-command generation. The features in this case are the number of peaks and the mean of the EEG signal during 1 s window. We tested the generated commands on a quadcopter in an open space. An average accuracy of 75.6% was achieved with fNIRS for four-command decoding and 86% with EEG for another four-command decoding. The testing results show the possibility of controlling a quadcopter online and in real-time using eight commands from the prefrontal and frontal cortices via the proposed hybrid EEG-fNIRS interface.
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Comparison of injury epidemiology between the Wenchuan and Lushan earthquakes in Sichuan, China.
Hu, Yang; Zheng, Xi; Yuan, Yong; Pu, Qiang; Liu, Lunxu; Zhao, Yongfan
2014-12-01
We aimed to compare injury characteristics and the timing of admissions and surgeries in the Wenchuan earthquake in 2008 and the Lushan earthquake in 2013. We retrospectively compared the admission and operating times and injury profiles of patients admitted to our medical center during both earthquakes. We also explored the relationship between seismic intensity and injury type. The time from earthquake onset to the peak in patient admissions and surgeries differed between the 2 earthquakes. In the Wenchuan earthquake, injuries due to being struck by objects or being buried were more frequent than other types of injuries, and more patients suffered injuries of the extremities than thoracic injuries or brain trauma. In the Lushan earthquake, falls were the most common injury, and more patients suffered thoracic trauma or brain injuries. The types of injury seemed to vary with seismic intensity, whereas the anatomical location of the injury did not. Greater seismic intensity of an earthquake is associated with longer delay between the event and the peak in patient admissions and surgeries, higher frequencies of injuries due to being struck or buried, and lower frequencies of injuries due to falls and injuries to the chest and brain. These insights may prove useful for planning rescue interventions in trauma centers near the epicenter.
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Soszynski, D; Chelminiak, M
2007-12-01
The purpose of this study was to investigate the role of neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) in the brain during development of fever in response to localized tissue inflammation caused by injection of turpentine in freely moving biotelemetered rats. To determine the role of both NOSs in turpentineinduced fever, we injected vinyl-L-NIO (N(5) - (1-Imino-3-butenyl) - ornithine (vLNIO), a selective nNOS inhibitor, and aminoguanidine hydrochloride, a selective iNOS inhibitor, intracerebroventricularly (i.c.v.) 5 h after turpentine injection. Rats responded with fever to intramuscular injection of 20 mul of turpentine that commenced about 5 - 6 h after injection and reached peak value between 9 - 11 h post-turpentine. The inhibition of nNOS as well as iNOS in the brain did not affect fever induced by turpentine. Fevers in control rats (treated i.c.v. with pyrogen-free water) and iNOS or nNOS inhibitor-i.c.v. treated rats injected with turpentine were essentially the same. Furthermore, on the basis of these data, we concluded that iNOS and nNOS inside the brain do not participate in generation of fever to turpentine in rats.
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Martynova, Olga V; Portnova, Galina V; Gladun, Ksenya V
2017-02-08
Clinical neurology is constantly searching for reliable indices of ischemic brain damage to prevent a possible development of stroke. We suggest that resting state electroencephalogram (rsEEG) with respect to other clinical data may provide important information about the severity of ischemia. We carried out correlation analysis of rsEEG, data of transcranial Doppler ultrasonography of head vessels, and clinical assessment scores collected from healthy volunteers and four groups of patients with mild chronic microvascular ischemia (CMI-1), moderate CMI (CMI-2), severe atrophy of the cerebral hemisphere, ischemic stroke in the left middle cerebral artery stroke, and ischemic stroke in the right middle cerebral artery stroke. Using independent component analysis and k-mean clustering of EEG data, we observed prominent changes in rsEEG reflected in specific distributions of spectral peaks in all groups of patients. We found a significant correlation of EEG spectral distribution and the blood flow velocity in coronal arteries, which was also affected by the severity of ischemia and the localization of stroke. Moreover, EEG spectral distribution was more indicative of early stages of ischemia than the blood flow velocity. Our data support the hypothesis that rsEEG may reflect altered neural activity caused by ischemic brain damage.
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Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields.
Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela
2016-06-21
An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform's size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke's brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.
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Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields
NASA Astrophysics Data System (ADS)
Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela
2016-06-01
An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform’s size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke’s brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.
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Operation Brain Trauma Therapy Extended Studies
2015-05-01
peaks in the TBI models. It is also possible that the use of a craniotomy in all 3 models results in an under- estimation of the potential benefit of...traditional strategies, namely, osmolar therapy (mannitol or hypertonic saline administration), CSF drainage , craniectomy, limitation of fluid administration
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NASA Astrophysics Data System (ADS)
Anusha, Chidambaram; Sankar, Renu; Varunkumar, Krishnamoorthy; Sivasindhuja, Gnanasambantham; Ravikumar, Vilwanathan
2017-12-01
The goal of this study is to establish Fourier transform-infrared (FTIR) spectroscopy as a diagnostic tool for allethrin-based mosquito coil smoke inhalation induced toxicity in mice. Primarily, we confirmed mosquito coil smoke inhalation toxicity in mice via reduced the body, organ weight and major vital organ tissue morphological structure changes. Furthermore, FTIR spectra was collected from control and mosquito coil smoke inhalation (8 h per day for 30 days) mice various tissues like liver, kidney, lung, heart and brain, to investigate the functional groups and their corresponding biochemical content variations. The FTIR spectra result shown major bio macromolecules such as protein and lipid functional peaks were shifted (decreased) in the mosquito coil smoke inhalation group as compared to control. The drastic peak shift was noticed in the liver, kidney followed by lung and brain. It is therefore concluded that the FTIR spectroscopy can be a successful detection tool in mosquito coil smoke inhalation toxicity.
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Traumatic brain injuries in children: A hospital-based study in Nigeria.
Udoh, David O; Adeyemo, Adebolajo A
2013-01-01
Traumatic Brain Injury (TBI) is a significant cause of morbidity and mortality worldwide. Our previous studies showed a high frequency of motor vehicle accidents among neurosurgical patients. However, there is a dearth of data on head injuries in children in Nigeria. To determine the epidemiology of paediatric traumatic brain injuries. This is a prospective analysis of paediatric head trauma at the University of Benin Teaching Hospital, a major referral centre for all traumatic brain injuries in Nigeria between October 2006 and September 2011. We studied the demographic, clinical and radiological data and treatment outcomes. Data was analysed using statistical package for the social sciences (SPSS) 16.0. We managed 127 cases of paediatric head injuries, 65 boys and 62 girls representing 13% of all head injuries managed over the 5-year period. They were aged 3 months to 17 years. The mean age was 7.4 years (median 7 years) with peak incidence occurring at 6-8 years i.e. 31 (24.4%) cases. Motor vehicle accidents resulted in 67.7%, falls 14% and violence 7%. The most frequent computed tomography finding was intracerebral haemorrhage. Mean duration of hospitalization was 18 days (median 11 days). Eleven patients died, mortality correlating well with severity and the presence of intracerebral haematoma. Head injuries in children are due to motor vehicle and motor vehicle-related accidents. Hence, rational priorities for prevention of head injuries in children should include prevention of vehicular, especially pedestrian, accidents in developing countries.
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The impact of verbal framing on brain activity evoked by emotional images.
Kisley, Michael A; Campbell, Alana M; Larson, Jenna M; Naftz, Andrea E; Regnier, Jesse T; Davalos, Deana B
2011-12-01
Emotional stimuli generally command more brain processing resources than non-emotional stimuli, but the magnitude of this effect is subject to voluntary control. Cognitive reappraisal represents one type of emotion regulation that can be voluntarily employed to modulate responses to emotional stimuli. Here, the late positive potential (LPP), a specific event-related brain potential (ERP) component, was measured in response to neutral, positive and negative images while participants performed an evaluative categorization task. One experimental group adopted a "negative frame" in which images were categorized as negative or not. The other adopted a "positive frame" in which the exact same images were categorized as positive or not. Behavioral performance confirmed compliance with random group assignment, and peak LPP amplitude to negative images was affected by group membership: brain responses to negative images were significantly reduced in the "positive frame" group. This suggests that adopting a more positive appraisal frame can modulate brain activity elicited by negative stimuli in the environment.
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Gutierrez, E; Huang, Y; Haglid, K; Bao, F; Hansson, H A; Hamberger, A; Viano, D
2001-03-01
Rapid head rotation is a major cause of brain damage in automobile crashes and falls. This report details a new model for rotational acceleration about the center of mass of the rabbit head. This allows the study of brain injury without translational acceleration of the head. Impact from a pneumatic cylinder was transferred to the skull surface to cause a half-sine peak acceleration of 2.1 x 10(5) rad/s2 and 0.96-ms pulse duration. Extensive subarachnoid hemorrhages and small focal bleedings were observed in the brain tissue. A pronounced reactive astrogliosis was found 8-14 days after trauma, both as networks around the focal hemorrhages and more diffusely in several brain regions. Astrocytosis was prominent in the gray matter of the cerebral cortex, layers II-V, and in the granule cell layer and around the axons of the pyramidal neurons in the hippocampus. The nuclei of cranial nerves, such as the hypoglossal and facial nerves, also showed intense astrocytosis. The new model allows study of brain injuries from head rotation in the absence of translational influences.
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Peak skin and eye lens radiation dose from brain perfusion CT based on Monte Carlo simulation.
Zhang, Di; Cagnon, Chris H; Villablanca, J Pablo; McCollough, Cynthia H; Cody, Dianna D; Stevens, Donna M; Zankl, Maria; Demarco, John J; Turner, Adam C; Khatonabadi, Maryam; McNitt-Gray, Michael F
2012-02-01
The purpose of our study was to accurately estimate the radiation dose to skin and the eye lens from clinical CT brain perfusion studies, investigate how well scanner output (expressed as volume CT dose index [CTDI(vol)]) matches these estimated doses, and investigate the efficacy of eye lens dose reduction techniques. Peak skin dose and eye lens dose were estimated using Monte Carlo simulation methods on a voxelized patient model and 64-MDCT scanners from four major manufacturers. A range of clinical protocols was evaluated. CTDI(vol) for each scanner was obtained from the scanner console. Dose reduction to the eye lens was evaluated for various gantry tilt angles as well as scan locations. Peak skin dose and eye lens dose ranged from 81 mGy to 348 mGy, depending on the scanner and protocol used. Peak skin dose and eye lens dose were observed to be 66-79% and 59-63%, respectively, of the CTDI(vol) values reported by the scanners. The eye lens dose was significantly reduced when the eye lenses were not directly irradiated. CTDI(vol) should not be interpreted as patient dose; this study has shown it to overestimate dose to the skin or eye lens. These results may be used to provide more accurate estimates of actual dose to ensure that protocols are operated safely below thresholds. Tilting the gantry or moving the scanning region further away from the eyes are effective for reducing lens dose in clinical practice. These actions should be considered when they are consistent with the clinical task and patient anatomy.
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Haebig, Eileen; Leonard, Laurence; Usler, Evan; Deevy, Patricia; Weber, Christine
2018-03-15
Previous behavioral studies have found deficits in lexical-semantic abilities in children with specific language impairment (SLI), including reduced depth and breadth of word knowledge. This study explored the neural correlates of early emerging familiar word processing in preschoolers with SLI and typical development. Fifteen preschoolers with typical development and 15 preschoolers with SLI were presented with pictures followed after a brief delay by an auditory label that did or did not match. Event-related brain potentials were time locked to the onset of the auditory labels. Children provided verbal judgments of whether the label matched the picture. There were no group differences in the accuracy of identifying when pictures and labels matched or mismatched. Event-related brain potential data revealed that mismatch trials elicited a robust N400 in both groups, with no group differences in mean amplitude or peak latency. However, the typically developing group demonstrated a more robust late positive component, elicited by mismatch trials. These initial findings indicate that lexical-semantic access of early acquired words, indexed by the N400, does not differ between preschoolers with SLI and typical development when highly familiar words are presented in isolation. However, the typically developing group demonstrated a more mature profile of postlexical reanalysis and integration, indexed by an emerging late positive component. The findings lay the necessary groundwork for better understanding processing of newly learned words in children with SLI.
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Auditory-evoked cortical activity: contribution of brain noise, phase locking, and spectral power
Harris, Kelly C.; Vaden, Kenneth I.; Dubno, Judy R.
2017-01-01
Background The N1-P2 is an obligatory cortical response that can reflect the representation of spectral and temporal characteristics of an auditory stimulus. Traditionally, mean amplitudes and latencies of the prominent peaks in the averaged response are compared across experimental conditions. Analyses of the peaks in the averaged response only reflect a subset of the data contained within the electroencephalogram (EEG) signal. We used single-trial analyses techniques to identify the contribution of brain noise, neural synchrony, and spectral power to the generation of P2 amplitude and how these variables may change across age group. This information is important for appropriate interpretation of event-related potentials (ERPs) results and in understanding of age-related neural pathologies. Methods EEG was measured from 25 younger and 25 older normal hearing adults. Age-related and individual differences in P2 response amplitudes, and variability in brain noise, phase locking value (PLV), and spectral power (4–8 Hz) were assessed from electrode FCz. Model testing and linear regression were used to determine the extent to which brain noise, PLV, and spectral power uniquely predicted P2 amplitudes and varied by age group. Results Younger adults had significantly larger P2 amplitudes, PLV, and power compared to older adults. Brain noise did not differ between age groups. The results of regression testing revealed that brain noise and PLV, but not spectral power were unique predictors of P2 amplitudes. Model fit was significantly better in younger than in older adults. Conclusions ERP analyses are intended to provide a better understanding of the underlying neural mechanisms that contribute to individual and group differences in behavior. The current results support that age-related declines in neural synchrony contribute to smaller P2 amplitudes in older normal hearing adults. Based on our results, we discuss potential models in which differences in neural synchrony and brain noise can account for associations with P2 amplitudes and behavior and potentially provide a better explanation of the neural mechanisms that underlie declines in auditory processing and training benefits. PMID:25046314
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Dispositional study of opioids in mice pretreated with sympathomimetic agents.
Dambisya, Y M; Chan, K; Wong, C L
1992-08-01
Brain and plasma levels of morphine and codeine were determined by an assay method involving solid-phase extraction and ion-pair reversed phase HPLC. Detection was by a variable wavelength UV-detector (for codeine) and an amperometric electro-chemical detector (for morphine) coupled in series. Ephedrine or phenylpropanolamine pretreatment did not interfere with the plasma disposition of morphine, evidenced by overlapping plasma concentration-time profiles. Brain opioid levels were equally unaffected by sympathomimetic pretreatment. The relative ratios of brain to plasma concentrations at the time corresponding to the respective peak anti-nociceptive activity for morphine and codeine revealed no significant differences. It is concluded that single doses of ephedrine and phenylpropanolamine do not affect the disposition of morphine and codeine in mice.
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NASA Astrophysics Data System (ADS)
Hramov, Alexander E.; Kharchenko, Alexander A.; Makarov, Vladimir V.; Khramova, Marina V.; Koronovskii, Alexey A.; Pavlov, Alexey N.; Dana, Syamal K.
2016-04-01
In the paper we study the mechanisms of phase synchronization in the adaptive model network of Kuramoto oscillators and the neural network of brain by consideration of the integral characteristics of the observed networks signals. As the integral characteristics of the model network we consider the summary signal produced by the oscillators. Similar to the model situation we study the ECoG signal as the integral characteristic of neural network of the brain. We show that the establishment of the phase synchronization results in the increase of the peak, corresponding to synchronized oscillators, on the wavelet energy spectrum of the integral signals. The observed correlation between the phase relations of the elements and the integral characteristics of the whole network open the way to detect the size of synchronous clusters in the neural networks of the epileptic brain before and during seizure.
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Stability in neurovascular function at 3800m.
Caldwell, Hannah G; Ainslie, Philip N; Ellis, Lindsay A; Phillips, Aaron A; Flück, Daniela
2017-12-01
Hypoxia-induced neurocognitive impairments have been of clinical interest for centuries. The mechanisms responsible for these neurocognitive impairments at altitude are unclear, but may relate to the uncoupling of local neural activity with appropriate changes in cerebral blood flow (CBF; i.e., functional hyperemia). At both sea level and following 3 and 7days at 3800m (Barcroft Research Lab, White Mountain, CA, USA), transcranial Doppler was used to index CBF during three separate tasks designed to evoke cerebral functional hyperemia in 11 healthy individuals (26.6±5.5yrs, 2 females). The tasks were: 1) Visual stimulation (VS), with measurement of anterior and posterior CBF; 2) Verbal fluency (VF), with measurement of bilateral CBF; and 3) Visuospatial task (VST), with measurement of bilateral CBF. The VS evoked an increase from baseline to percent peak response in both the posterior (15.2±7.7%, P<0.01) and anterior (7.6±3.5%, P<0.01) cerebral hemispheres; however, the percent peak response was higher in the posterior brain, where visual regions are localized (P=0.01). The left-sided task, VF, resulted in an increase in both the left (12.2±4.0%, P<0.01) and right (9.0±4.4%, P<0.01) cerebral hemispheres; however, the percent peak response was higher in the left brain, where language centers are located (P<0.01). The right-sided task, VST, evoked an increase in both the left (13.9±7.1%, P<0.01) and right (16.8±6.7%, P<0.01) cerebral hemispheres; however, the percent peak response was higher in the right brain, where visuospatial regions are located (P<0.01). Each cerebral functional hyperemia response for all three tasks was unaffected by high altitude exposure (P>0.05). Overall, at least at 3800m, neurovascular function is intact with exposure to 3 and 7days of high altitude and likely does not explain the previous reports of neurocognitive impairment. Copyright © 2017 Elsevier Inc. All rights reserved.
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Brain CYP2B induction can decrease nicotine levels in the brain.
Garcia, Kristine L P; Lê, Anh Dzung; Tyndale, Rachel F
2017-09-01
Nicotine can be metabolized by the enzyme CYP2B; brain CYP2B is higher in rats and monkeys treated with nicotine, and in human smokers. A 7-day nicotine treatment increased CYP2B expression in rat brain but not liver, and decreased the behavioral response and brain levels (ex vivo) to the CYP2B substrate propofol. However, the effect of CYP2B induction on the time course and levels of circulating brain nicotine in vivo has not been demonstrated. Using brain microdialysis, nicotine levels following a subcutaneous nicotine injection were measured on day one and after a 7-day nicotine treatment. There was a significant time x treatment interaction (p = 0.01); peak nicotine levels (15-45 minutes post-injection) were lower after treatment (p = 0.04) consistent with CYP2B induction. Following a two-week washout period, brain nicotine levels increased to day one levels (p = 0.02), consistent with brain CYP2B levels returning to baseline. Brain pretreatment of the CYP2B inhibitor, C8-xanthate, increased brain nicotine levels acutely and after 7-day nicotine treatment, indicating the alterations in brain nicotine levels were due to changes in brain CYP2B activity. Plasma nicotine levels were not altered for any time or treatment sampled, confirming no effect on peripheral nicotine metabolism. These results demonstrate that chronic nicotine, by increasing brain CYP2B activity, reduces brain nicotine levels, which could alter nicotine's reinforcing effects. Higher brain CYP2B levels in smokers could lower brain nicotine levels; as this induction would occur following continued nicotine exposure it could increase withdrawal symptoms and contribute to sustaining smoking behavior. © 2016 Society for the Study of Addiction.
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Nirogi, Ramakrishna; Ajjala, Devender Reddy; Kandikere, Vishwottam; Aleti, Raghupathi; Pantangi, Hanumanth Rao; Srikakolapu, Surya Rao; Benade, Vijay; Bhyrapuneni, Gopinadh; Vurimindi, Himabindu
2013-01-01
A sensitive LC-MS/MS method was developed and validated for the quantification of almotriptan in rat brain and blood dialysates. Almotriptan is a 5HT1B/1D receptor agonist used for the treatment of migraine pain. Method consists of rapid gradient elution program with 10mM ammonium formate (pH 3) and acetonitrile on a Xbridge column. The MRM transitions monitored were m/z 336.2-58.1 for almotriptan and m/z 448.2-285.3 for the IS. The assay was linear in the range of 0.1-20 ng/ml, with acceptable precision and accuracy along with adequate sensitivity. The between batch accuracy was in the range of 99.0-104.3% with precision in between 0.6% and 5.8%. Microdialysis is an important sampling technique, with the capability of capturing the concentrations of various analytes in different bio fluids, at a single time point. This method was applied to quantify brain and blood dialysate samples obtained from a microdialysis study of rats treated with almotriptan (10mg/kg, p.o.). In vivo recovery experiments were performed to correct the dialysate concentrations into extracellular concentrations. Mean peak dialysate concentrations of almotriptan were found to be 152 ± 78 and 7.4 ± 1.0 ng/ml in blood and prefrontal cortex, respectively. The brain penetration of almotriptan is characterized by the AUCbrain/AUCblood found to be 0.07 ± 0.05. The results revealed the importance of measuring the unbound almotriptan concentrations in the brain over the blood for understanding its PK/PD relationship. Copyright © 2013 Elsevier B.V. All rights reserved.
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Shen, Erica Y.; Ahern, Todd H.; Cheung, Iris; Straubhaar, Juerg; Dincer, Aslihan; Houston, Isaac; de Vries, Geert J.; Akbarian, Schahram; Forger, Nancy G.
2014-01-01
Many neurological and psychiatric disorders exhibit gender disparities, and sex differences in the brain likely explain some of these effects. Recent work in rodents points to a role for epigenetics in the development or maintenance of neural sex differences, although genome-wide studies have so far been lacking. Here we review the existing literature on epigenetics and brain sexual differentiation and present preliminary analyses on the genome-wide distribution of histone-3 lysine-4 trimethylation in a sexually dimorphic brain region in male and female mice. H3K4me3 is a histone mark primarily organized as ‘peaks’ surrounding the transcription start site of active genes. We microdissected the bed nucleus of the stria terminalis and preoptic area (BNST/POA) in adult male and female mice and used ChIP-Seq to compare the distribution of H3K4me3 throughout the genome. We found 248 genes and loci with a significant sex difference in H3K4me3. Of these, the majority (71%) had larger H3K4me3 peaks in females. Comparisons with existing databases indicate that genes and loci with increased H3K4me3 in females are associated with synaptic function and with expression atlases from related brain areas. Based on RT-PCR, only a minority of genes with a sex difference in H3K4me3 has detectable sex differences in expression at baseline conditions. Together with previous findings, our data suggest there may be sex biases in the use of epigenetic marks. Such biases could underlie sex differences in vulnerabilities to drugs or diseases that disrupt specific epigenetic processes. PMID:25131640
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Kainz, Wolfgang; Alesch, François; Chan, Dulciana Dias
2003-01-01
Background The purpose was to investigate mobile phone interference with implantable deep brain stimulators by means of 10 different 900 Mega Hertz (MHz) and 10 different 1800 MHz GSM (Global System for Mobile Communications) mobile phones. Methods All tests were performed in vitro using a phantom especially developed for testing with deep brain stimulators. The phantom was filled with liquid phantom materials simulating brain and muscle tissue. All examinations were carried out inside an anechoic chamber on two implants of the same type of deep brain stimulator: ITREL-III from Medtronic Inc., USA. Results Despite a maximum transmitted peak power of mobile phones of 1 Watt (W) at 1800 MHz and 2 W at 900 MHz respectively, no influence on the ITREL-III was found. Neither the shape of the pulse form changed nor did single pulses fail. Tests with increased transmitted power using CW signals and broadband dipoles have shown that inhibition of the ITREL-III occurs at frequency dependent power levels which are below the emissions of GSM mobile phones. The ITREL-III is essentially more sensitive at 1800 MHz than at 900 MHz. Particularly the frequency range around 1500 MHz shows a very low interference threshold. Conclusion These investigations do not indicate a direct risk for ITREL-III patients using the tested GSM phones. Based on the interference levels found with CW signals, which are below the mobile phone emissions, we recommend similar precautions as for patients with cardiac pacemakers: 1. The phone should be used at the ear at the opposite side of the implant and 2. The patient should avoid carrying the phone close to the implant. PMID:12773204
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Yang, Shudong; Sun, Rongchao; Zhou, Zhiyi; Zhou, Jing; Liang, Jiabei; Mu, Huijun
2014-09-01
Amyloid-β (Aβ) protein and its precursor, amyloid-β precursor protein (β-APP), have traditionally been used in the diagnosis of Alzheimer disease. Their use in diagnosis of traumatic brain injury by forensic analysis is becoming more widespread. However, to date, no reliable small animal model exists to evaluate these brain injury indicators. To address this, we have studied primary brain-stem injury in rats to assess the appearance of diffuse axonal injury in brain sections and correlate these findings with appearance of Aβ and relative β-APP mRNA levels. Using an EnVision 2-step immunohistochemical staining method to measure axon diameter, we found that there was significant difference in axon diameters within the medulla oblongata and several time points after brain injury, ranging from 3 to 24 hours. In addition, mRNA expression levels of β-APP increased following brain injury, peaking 3 hours following injury and decreasing back to baseline levels by 24 hours after injury. These results suggest that using immunohistochemistry and reverse transcription-polymerase chain reaction to detect changes in Aβ-associated axonal changes and β-APP mRNA levels, respectively, can be useful for the diagnosis of diffuse axonal injury during autopsy at early time points following fatal brain injury.
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Yang, Yan-Fang; Zhang, Lei; Yang, Xiu-Wei
2018-01-20
Angelicae Pubescentis Radix (APR) is a widely-used traditional Chinese medicine. Pharmacological studies have begun to probe its biological activities on neurological disorders recently. To assess the brain penetration and distribution of APR, a validated ultra-performance liquid chromatography tandem mass spectrometry method was applied to the simultaneous determinations of the main coumarins from APR in the rat cerebrospinal fluid (CSF) and brain after oral administration of APR extract, including psoralen, xanthotoxin, bergapten, isoimperatorin, columbianetin, columbianetin acetate, columbianadin, oxypeucedanin hydrate, angelol B, osthole, meranzin hydrate and nodakenetin. Most of the tested coumarins entered the rat CSF and brain quickly, and double-peak phenomena in concentration-time curves were similar to those of their plasma pharmacokinetics. Columbianetin had the highest concentration in the CSF and brain, while psoralen and columbianetin acetate had the largest percent of CSF/plasma and brain/plasma, indicating that these three coumarins may be worthy of further research on the possible nervous effects. Correlations between the in vivo brain distributions and plasma pharmacokinetics of these coumarins were well verified. These results provided valuable information for the overall in vivo brain distribution characteristics of APR and also for its further studies on the active substances for the central nervous system.
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Compact diode laser source for multiphoton biological imaging
Niederriter, Robert D.; Ozbay, Baris N.; Futia, Gregory L.; Gibson, Emily A.; Gopinath, Juliet T.
2016-01-01
We demonstrate a compact, pulsed diode laser source suitable for multiphoton microscopy of biological samples. The center wavelength is 976 nm, near the peak of the two-photon cross section of common fluorescent markers such as genetically encoded green and yellow fluorescent proteins. The laser repetition rate is electrically tunable between 66.67 kHz and 10 MHz, with 2.3 ps pulse duration and peak powers >1 kW. The laser components are fiber-coupled and scalable to a compact package. We demonstrate >600 μm depth penetration in brain tissue, limited by laser power. PMID:28101420
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Pereira, Glauber B.; Meng, Fanxue; Kockara, Neriman T.; Yang, Baoli; Wight, Patricia A.
2012-01-01
Myelin proteolipid protein gene (Plp1) expression is temporally regulated in brain, which peaks during the active myelination period of CNS development. Previous studies with Plp1-lacZ transgenic mice demonstrated that (mouse) Plp1 intron 1 DNA is required for high levels of expression in oligodendrocytes. Deletion-transfection analysis revealed the intron contains a single positive regulatory element operative in the N20.1 oligodendroglial cell line, which was named ASE (antisilencer/enhancer) based on its functional properties in these cells. To investigate the role of the ASE in vivo, the element was deleted from the native gene in mouse using a Cre/lox strategy. While removal of the ASE from Plp1-lacZ constructs profoundly decreased expression in transfected oligodendroglial cell lines (N20.1 and Oli-neu), the element was dispensable to achieve normal levels of Plp1 gene expression in mouse during development (except perhaps at postnatal day 15) and throughout the remyelination period following cuprizone-induced (acute) demyelination. Thus, it is possible that the ASE is nonfunctional in vivo, or that loss of the ASE from the native gene in mouse can be compensated for by the presence of other regulatory elements within the Plp1 gene. PMID:23157328
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Intranasal Administration of PACAP: Uptake by Brain and Brain Region Targeting with Cyclodextrins
Nonaka, Naoko; Farr, Susan A.; Nakamachi, Tomoya; Morley, John E.; Nakamura, Masanori; Shioda, Seiji; Banks, William A.
2012-01-01
Pituitary adenylate cyclase activating polypeptide (PACAP) is a potent neurotrophic and neuroprotectant that is transported across the blood-brain barrier in amounts sufficient to affect brain function. However, its short half-life in blood makes it difficult to administer peripherally. Here, we determined whether the radioactively labeled 38 amino acid form of PACAP can enter the brain after intranasal (i.n.) administration. Occipital cortex and striatum were the regions with the highest uptake, peaking at levels of about 2-4 percent of the injected dose per g of brain region. Inclusion of unlabeled PACAP greatly increased retention of I-PACAP by brain probably because of inhibition of the brain-to-blood efflux transporter for PACAP located at the blood-brain barrier. Sufficient amounts of PACAP could be delivered to the brain to affect function as shown by improvement of memory in aged SAMP8 mice, a model of Alzheimer’s disease. We found that each of three cyclodextrins when included in the i.n. injection produced a unique distribution pattern of I-PACAP among brain regions. As examples, β-cyclodextrin greatly increased uptake by the occipital cortex and hypothalamus, α-cyclodextrin increased uptake by the olfactory bulb and decreased uptake by the occipital cortex and striatum, and (2-hydropropyl)-β-cyclodextrin increased uptake by the thalamus and decreased uptake by the striatum. These results show that therapeutic amounts of PACAP can be delivered to the brain by intranasal administration and that cyclodextrins may be useful in the therapeutic targeting of peptides to specific brain regions. PMID:22687366
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Willoughby, Teena; Good, Marie; Adachi, Paul J C; Hamza, Chloe; Tavernier, Royette
2013-12-01
The adolescent age period is often characterized as a health paradox because it is a time of extensive increases in physical and mental capabilities, yet overall mortality/morbidity rates increase significantly from childhood to adolescence, often due to preventable causes such as risk taking. Asynchrony in developmental time courses between the affective/approach and cognitive control brain systems, as well as the ongoing maturation of neural connectivity are thought to lead to increased vulnerability for risk taking in adolescence. A critical analysis of the frequency of risk taking behaviors, as well as mortality and morbidity rates across the lifespan, however, challenges the hypothesis that the peak of risk taking occurs in middle adolescence when the asynchrony between the different developmental time courses of the affective/approach and cognitive control systems is the largest. In fact, the highest levels of risk taking behaviors, such as alcohol and drug use, often occur among emerging adults (e.g., university/college students), and highlight the role of the social context in predicting risk taking behavior. Moreover, risk taking is not always unregulated or impulsive. Future research should broaden the scope of risk taking to include risks that are relevant to older adults, such as risky financial investing, gambling, and marital infidelity. In addition, a lifespan perspective, with a focus on how associations between neural systems and behavior are moderated by context and trait-level characteristics, and which includes diverse samples (e.g., divorced individuals), will help to address some important limitations in the adolescent brain development and risk taking literature. Copyright © 2013 Elsevier Inc. All rights reserved.
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Williams, Victoria; Hayes, Jasmeet P.; Forman, Daniel E.; Salat, David H.; Sperling, Reisa A.; Verfaellie, Mieke; Hayes, Scott M.
2016-01-01
Aging is associated with reductions in gray matter volume and cortical thickness. One factor that may play a role in mitigating age-associated brain decline is cardiorespiratory fitness (CRF). Although previous work has identified a positive association between CRF and gray matter volume, the relationship between CRF and cortical thickness, which serves as a more sensitive indicator of gray matter integrity, has yet to be assessed in healthy young and older adults. To address this gap in the literature, 32 young and 29 older adults completed treadmill-based progressive maximal exercise testing to assess CRF (peak VO2), and structural magnetic resonance imaging (MRI) to determine vertex-wise surface-based cortical thickness metrics. Results indicated a significant CRF by age group interaction such that Peak VO2 was associated with thicker cortex in older adults but with thinner cortex in young adults. Notably, the majority of regions demonstrating a positive association between peak VO2 and cortical thickness in older adults overlapped with brain regions showing significant age-related cortical thinning. Further, when older adults were categorized as high or low fit based on normative data, we observed a stepwise pattern whereby cortex was thickest in young adults, intermediate in high fit older adults and thinnest in low fit older adults. Overall, these results support the notion that CRF-related neuroplasticity may reduce although not eliminate age-related cortical atrophy. PMID:27989841
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Behavioral, hyperthermic and pharmacokinetic profile of para-methoxymethamphetamine (PMMA) in rats.
Páleníček, Tomáš; Balíková, Marie; Rohanová, Miroslava; Novák, Tomáš; Horáček, Jiří; Fujáková, Michaela; Höschl, Cyril
2011-03-01
Despite poisoning with the ecstasy substitute para-methoxymethamphetamine (PMMA) being typically associated with severe hyperthermia and death, behavioral and toxicological data on this drug are missing. Herein we present the behavioral profile of PMMA, its hyperthermic potency and pharmacokinetic profile in rats. The effects of PMMA 5 and 20 mg/kg on locomotion, on prepulse inhibition (PPI) of acoustic startle reaction (ASR), on body temperature under isolated and crowded conditions and on the pharmacokinetics analyzed with gas chromatography mass spectrometry (GC-MS) were evaluated. PMMA increased overall locomotion with the higher dose showing a biphasic effect. PPI was decreased dose-dependently. The hyperthermic response was present only with PMMA 20 mg/kg and was accompanied by extensive perspiration under crowded conditions. Serum levels of PMMA peaked at approximately 30 min after both treatments; on the contrary the maximum brain concentrations of PMMA at 20 mg/kg peaked approximately 1h after the administration, which was rather delayed compared to maximum after 5mg/kg dose. These data indicate that PMMA has a similar behavioral profile to stimulants and hallucinogens and that the toxicity might be increased in a crowded environment. High doses of PMMA have a gradual penetration to the brain which might lead to the delayed peak concentrations and prolonged effects of the drug. Copyright © 2010 Elsevier Inc. All rights reserved.
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Williams, Victoria J; Hayes, Jasmeet P; Forman, Daniel E; Salat, David H; Sperling, Reisa A; Verfaellie, Mieke; Hayes, Scott M
2017-02-01
Aging is associated with reductions in gray matter volume and cortical thickness. One factor that may play a role in mitigating age-associated brain decline is cardiorespiratory fitness (CRF). Although previous work has identified a positive association between CRF and gray matter volume, the relationship between CRF and cortical thickness, which serves as a more sensitive indicator of gray matter integrity, has yet to be assessed in healthy young and older adults. To address this gap in the literature, 32 young and 29 older adults completed treadmill-based progressive maximal exercise testing to assess CRF (peak VO 2 ), and structural magnetic resonance imaging (MRI) to determine vertex-wise surface-based cortical thickness metrics. Results indicated a significant CRF by age group interaction such that Peak VO 2 was associated with thicker cortex in older adults but with thinner cortex in young adults. Notably, the majority of regions demonstrating a positive association between peak VO 2 and cortical thickness in older adults overlapped with brain regions showing significant age-related cortical thinning. Further, when older adults were categorized as high or low fit based on normative data, we observed a stepwise pattern whereby cortex was thickest in young adults, intermediate in high fit older adults and thinnest in low fit older adults. Overall, these results support the notion that CRF-related neuroplasticity may reduce although not eliminate age-related cortical atrophy. Published by Elsevier Inc.
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Magnetic resonance spectroscopy of the human brain
NASA Astrophysics Data System (ADS)
Strózik-Kotlorz, D.
2014-01-01
I give a brief description of the magnetic resonance spectroscopy (MRS) in the human brain examinations. MRS allows a noninvasive chemical analysis of the brain using a standard high field MR system. Nowadays, the dominant form of MR brain spectroscopy is proton spectroscopy. Two main techniques of MRS, which utilize the chemical shift of metabolites in the external magnetic field, are SVS (single voxel) and CSI (single slice). The major peaks in the spectrum of a normal brain include NAA, Cr, Cho and m-Ins, which are neuronal, energetic, membrane turnover and glial markers, respectively. In disease, two pathological metabolites can be found in the brain spectra: Lac, which is end product of anaerobic glycolysis and Lip, which is a marker of membrane breakdown, occurring in necrosis. The common way to analyze clinical spectra is to determine metabolite ratios, e.g. NAA/Cr, Cho/Cr, Cho/NAA. This analysis permits a safe and noninvasive examination of the brain tissue as each disease state has its own characteristic spectroscopic image. MRS is a valuable diagnostic tool in such clinical applications as detecting brain tumors and differentiating tumors from inflammatory and infectious processes. Proton MRS is also very helpful in diagnostic of ischemic lesions, Alzheimer's disease and hepatic encephalopathy. The MRS brain spectra should always be correlated with the Magnetic Resonance Imaging (MRI) results and alone cannot make neurological diagnosis.
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Alvarez, Tara L; Vicci, Vincent R; Alkan, Yelda; Kim, Eun H; Gohel, Suril; Barrett, Anna M; Chiaravalloti, Nancy; Biswal, Bharat B
2010-12-01
This research quantified clinical measurements and functional neural changes associated with vision therapy in subjects with convergence insufficiency (CI). Convergence and divergence 4° step responses were compared between 13 control adult subjects with normal binocular vision and four CI adult subjects. All CI subjects participated in 18 h of vision therapy. Clinical parameters quantified throughout the therapy included: nearpoint of convergence, recovery point of convergence, positive fusional vergence at near, near dissociated phoria, and eye movements that were quantified using peak velocity. Neural correlates of the CI subjects were quantified with functional magnetic resonance imaging scans comparing random vs. predictable vergence movements using a block design before and after vision therapy. Images were quantified by measuring the spatial extent of activation and the average correlation within five regions of interests (ROI). The ROIs were the dorsolateral prefrontal cortex, a portion of the frontal lobe, part of the parietal lobe, the cerebellum, and the brain stem. All measurements were repeated 4 months to 1 year post-therapy in three of the CI subjects. Convergence average peak velocities to step stimuli were significantly slower (p = 0.016) in CI subjects compared with controls; however, significant differences in average peak velocities were not observed for divergence step responses (p = 0.30). The investigation of CI subjects participating in vision therapy showed that the nearpoint of convergence, recovery point of convergence, and near dissociated phoria significantly decreased. Furthermore, the positive fusional vergence, average peak velocity from 4° convergence steps, and the amount of functional activity within the frontal areas, cerebellum, and brain stem significantly increased. Several clinical and cortical parameters were significantly correlated. Convergence peak velocity was significantly slower in CI subjects compared with controls, which may result in asthenopic complaints reported by the CI subjects. Vision therapy was associated with and may have evoked clinical and cortical activity changes.
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Huang, Chi-Wei; Hsu, Shih-Wei; Tsai, Shih-Jen; Chen, Nai-Ching; Liu, Mu-En; Lee, Chen-Chang; Huang, Shu-Hua; Chang, Weng-Neng; Chang, Ya-Ting; Tsai, Wan-Chen; Chang, Chiung-Chih
2017-01-18
Inflammatory processes play a pivotal role in the degenerative process of Alzheimer's disease. In humans, a biallelic (C/T) polymorphism in the promoter region (position-511) (rs16944) of the interleukin-1 beta gene has been significantly associated with differences in the secretory capacity of interleukin-1 beta. In this study, we investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer's disease. We enrolled a total of 135 patients with Alzheimer's disease (65 males, 70 females), and investigated their gray matter structural covariance networks using 3D T1 magnetic resonance imaging and their white matter macro-structural integrities using fractional anisotropy. The patients were classified into two genotype groups: C-carriers (n = 108) and TT-carriers (n = 27), and the structural covariance networks were constructed using seed-based analysis focusing on the default mode network medial temporal or dorsal medial subsystem, salience network and executive control network. Neurobehavioral scores were used as the major outcome factors for clinical correlations. There were no differences between the two genotype groups in the cognitive test scores, seed, or peak cluster volumes and white matter fractional anisotropy. The covariance strength showing C-carriers > TT-carriers was the entorhinal-cingulum axis. There were two peak clusters (Brodmann 6 and 10) in the salience network and four peak clusters (superior prefrontal, precentral, fusiform, and temporal) in the executive control network that showed C-carriers < TT-carriers in covariance strength. The salience network and executive control network peak clusters in the TT group and the default mode network peak clusters in the C-carriers strongly predicted the cognitive test scores. Interleukin-1 beta C-511 T polymorphism modulates the structural covariance strength on the anterior brain network and entorhinal-interconnected network which were independent of the white matter tract integrity. Depending on the specific C-511 T genotype, different network clusters could predict the cognitive tests.
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Alvarez, Tara L.; Vicci, Vincent R.; Alkan, Yelda; Kim, Eun H.; Gohel, Suril; Barrett, Anna M.; Chiaravalloti, Nancy; Biswal, Bharat B.
2011-01-01
Purpose This research quantified clinical measurements and functional neural changes associated with vision therapy in subjects with convergence insufficiency (CI). Methods Convergence and divergence 4° step responses were compared between 13 control adult subjects with normal binocular vision and four CI adult subjects. All CI subjects participated in 18 h of vision therapy. Clinical parameters quantified throughout the therapy included: nearpoint of convergence, recovery point of convergence, positive fusional vergence at near, near dissociated phoria, and eye movements that were quantified using peak velocity. Neural correlates of the CI subjects were quantified with functional magnetic resonance imaging scans comparing random vs. predictable vergence movements using a block design before and after vision therapy. Images were quantified by measuring the spatial extent of activation and the average correlation within five regions of interests (ROI). The ROIs were the dorsolateral prefrontal cortex, a portion of the frontal lobe, part of the parietal lobe, the cerebellum, and the brain stem. All measurements were repeated 4 months to 1 year post-therapy in three of the CI subjects. Results Convergence average peak velocities to step stimuli were significantly slower (p = 0.016) in CI subjects compared with controls; however, significant differences in average peak velocities were not observed for divergence step responses (p = 0.30). The investigation of CI subjects participating in vision therapy showed that the nearpoint of convergence, recovery point of convergence, and near dissociated phoria significantly decreased. Furthermore, the positive fusional vergence, average peak velocity from 4° convergence steps, and the amount of functional activity within the frontal areas, cerebellum, and brain stem significantly increased. Several clinical and cortical parameters were significantly correlated. Conclusions Convergence peak velocity was significantly slower in CI subjects compared with controls, which may result in asthenopic complaints reported by the CI subjects. Vision therapy was associated with and may have evoked clinical and cortical activity changes. PMID:21057347
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Brain metabolites in autonomic regulatory insular sites in heart failure.
Woo, Mary A; Yadav, Santosh K; Macey, Paul M; Fonarow, Gregg C; Harper, Ronald M; Kumar, Rajesh
2014-11-15
Autonomic, pain, and neuropsychologic comorbidities appear in heart failure (HF), likely resulting from brain changes, indicated as loss of structural integrity and functional deficits. Among affected brain sites, the anterior insulae are prominent in serving major regulatory roles in many of the disrupted functions commonly seen in HF. Metabolite levels, including N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (MI), could indicate the nature of anterior insula tissue injury in HF. The study aim was to assess anterior insular metabolites to determine processes mediating autonomic, pain, and neuropsychologic disruptions in HF. We performed magnetic resonance spectroscopy in bilateral anterior insulae in 11 HF and 53 controls, using a 3.0-Tesla magnetic resonance imaging scanner. Peaks for NAA at 2.02 ppm, Cr at 3.02 ppm, Cho at 3.2 ppm, and MI at 3.56 ppm were assigned, peak areas were calculated, and metabolites were expressed as ratios, including NAA/Cr, Cho/Cr, and MI/Cr. HF patients showed significantly increased Cho/Cr ratios, indicative of glial proliferation or injury, on the left anterior insula, and reduced NAA/Cr levels, suggesting neuronal loss/dysfunction, on the right anterior insula over controls. No differences in MI/Cr ratios appeared between groups. Right anterior insular neuronal loss and left glial alterations may contribute to distorted autonomic, pain, and neuropsychologic functions found in HF. Copyright © 2014 Elsevier B.V. All rights reserved.
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Baltus, Alina; Herrmann, Christoph Siegfried
2016-06-01
Oscillatory EEG activity in the human brain with frequencies in the gamma range (approx. 30-80Hz) is known to be relevant for a large number of cognitive processes. Interestingly, each subject reveals an individual frequency of the auditory gamma-band response (GBR) that coincides with the peak in the auditory steady state response (ASSR). A common resonance frequency of auditory cortex seems to underlie both the individual frequency of the GBR and the peak of the ASSR. This review sheds light on the functional role of oscillatory gamma activity for auditory processing. For successful processing, the auditory system has to track changes in auditory input over time and store information about past events in memory which allows the construction of auditory objects. Recent findings support the idea of gamma oscillations being involved in the partitioning of auditory input into discrete samples to facilitate higher order processing. We review experiments that seem to suggest that inter-individual differences in the resonance frequency are behaviorally relevant for gap detection and speech processing. A possible application of these resonance frequencies for brain computer interfaces is illustrated with regard to optimized individual presentation rates for auditory input to correspond with endogenous oscillatory activity. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2015 Elsevier B.V. All rights reserved.
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Schültke, Elisabeth; Trippel, Michael; Bräuer-Krisch, Elke; Renier, Michel; Bartzsch, Stefan; Requardt, Herwig; Döbrössy, Máté D; Nikkhah, Guido
2013-01-01
We have conducted the first in-vivo experiments in pencilbeam irradiation, a new synchrotron radiation technique based on the principle of microbeam irradiation, a concept of spatially fractionated high-dose irradiation. In an animal model of adult C57 BL/6J mice we have determined technical and physiological limitations with the present technical setup of the technique. Fifty-eight animals were distributed in eleven experimental groups, ten groups receiving whole brain radiotherapy with arrays of 50 µm wide beams. We have tested peak doses ranging between 172 Gy and 2,298 Gy at 3 mm depth. Animals in five groups received whole brain radiotherapy with a center-to-center (ctc) distance of 200 µm and a peak-to-valley ratio (PVDR) of ∼ 100, in the other five groups the ctc was 400 µm (PVDR ∼ 400). Motor and memory abilities were assessed during a six months observation period following irradiation. The lower dose limit, determined by the technical equipment, was at 172 Gy. The LD50 was about 1,164 Gy for a ctc of 200 µm and higher than 2,298 Gy for a ctc of 400 µm. Age-dependent loss in motor and memory performance was seen in all groups. Better overall performance (close to that of healthy controls) was seen in the groups irradiated with a ctc of 400 µm.
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Brain Metabolites in Autonomic Regulatory Insular Sites in Heart Failure
Woo, Mary A.; Yadav, Santosh K.; Macey, Paul M.; Fonarow, Gregg C.; Harper, Ronald M.; Kumar, Rajesh
2014-01-01
Autonomic, pain, and neuropsychologic comorbidities appear in heart failure (HF), likely resulting from brain changes, indicated as loss of structural integrity and functional deficits. Among affected brain sites, the anterior insulae are prominent in serving major regulatory roles in many of the disrupted functions commonly seen in HF. Metabolite levels, including N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (MI), could indicate the nature of anterior insula tissue injury in HF. The study aim was to assess anterior insular metabolites to determine processes mediating autonomic, pain, and neuropsychologic disruptions in HF. We performed magnetic resonance spectroscopy in bilateral anterior insulae in 11 HF and 53 controls, using a 3.0-Tesla magnetic resonance imaging scanner. Peaks for NAA at 2.02ppm, Cr at 3.02ppm, Cho at 3.2ppm, and MI at 3.56ppm were assigned, peak areas calculated, and metabolites expressed as ratios, including NAA/Cr, Cho/Cr, and MI/Cr. HF patients showed significantly increased Cho/Cr ratios, indicative of glial proliferation or injury, on the left anterior insula, and reduced NAA/Cr levels, suggesting neuronal loss/dysfunction, on the right anterior insula over controls. No differences in MI/Cr ratios appeared between groups. Right anterior insular neuronal loss and left glial alterations may contribute to distorted autonomic, pain, and neuropsychologic functions found in HF. PMID:25248953
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Activation of the mesocortical dopamine system by feeding: lack of a selective response to stress.
Taber, M T; Fibiger, H C
1997-03-01
There is wide agreement that catecholamine systems in the prefrontal cortex are activated by stressful stimuli. To date, however, the extent to which other stimuli can increase the activity of these systems has received little attention. In the present study, the effects of tail pinch stress and feeding on dopamine and noradrenaline release in the prefrontal cortex of rats were examined using in vivo brain microdialysis. Both stimuli increased dopamine release, with peak effects reaching 212% above baseline for tail pinch and 165% above baseline for feeding. The effects of the two stimuli on peak dopamine release were not significantly different. Both stimuli also significantly increased noradrenaline release, with peak effects reaching 128% above baseline for tail pinch and 98% above baseline for feeding. The effects of the two stimuli on peak noradrenaline release were not significantly different. These results indicate that activation of catecholaminergic afferents to the prefrontal cortex is not specific to stress, but also occurs in response to non-stressors with positive motivational valence.
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Effects of acute brainstem compression on auditory brainstem response in the guinea pig.
Tu, T Y; Yu, L H; Chiu, J H; Shu, C H; Shiao, A S; Lien, C F
1998-11-01
The purpose of this study was to establish the norm for parameters of auditory brainstem response (ABR) in the guinea pig and to investigate if acute brainstem compression results in significant changes to these parameters. Thirty-six guinea pigs with positive Preyer's reflex were anesthetized. A craniectomy was performed to remove the right occipital bone and the dura mater was opened to expose the brain, cerebellum and cerebellopontine angle (CPA). A small inflatable balloon was placed into the CPA precisely and slowly. ABR was recorded before incision of the skin as a baseline value, after placement and after inflation of the balloon with water at 0.1-ml intervals. Five stable peaks were recorded in 27 experimental animals. When the balloon was inflated with 0.1 ml water, the absolute latency (AL) of peaks IV and V and the interpeak latency (IPL) of peaks III and IV, and IV and V were prolonged. The amplitude ratios (AR) of peaks II, III, IV and V to peak I decreased. Inflation of the balloon with 0.2 ml of water caused further elongation of ALs of peaks IV and V and decreases in each AR. When the balloon volume increased to 0.3 ml, peak V became unrecognizable and peaks III and IV showed significant elongation of AL; peaks I and II did not show significant change in ALs. Further increase of the balloon volume to 0.4 ml resulted in disappearance of peaks III, IV and V; AL of peak II was also elongated. However, the amplitude and AL of peak I remained unchanged. Similar changes were observed in IPLs. This study establishes the norm of parameters of ABR in guinea pigs and demonstrates that acute brainstem compression causes elongation of ALs and IPLs of peaks II, III, IV and V. This suggests that peaks II, III, IV and V come from the brainstem and that peak I is not generated from the brainstem in the guinea pig.
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Checler, F; Vincent, J P; Kitabgi, P
1983-12-01
The present study was designed to compare the susceptibility of neurotensin (NT), [3H]NT, [D-Tyr11]NT and [D-Phe11]NT to degradation by 1) rat brain synaptic membranes in vitro and 2) after i.c.v. administration in the rat in vivo. Degradation was assessed by purifying the peptides using reverse phase high-performance liquid chromatography and by measuring the amount of radioactive or absorbing (OD 230) material under each peptide peak. In contrast to NT, [D-Tyr11]NT and [D-Phe11]NT were resistant to degradation by brain synaptic peptidases in vitro. Furthermore, NT was rapidly metabolized in brain tissues after i.c.v. administration, whereas [D-Tyr11]NT was metabolically stable. The present data confirm the central role of NT residue Tyr11 in the mechanisms of NT inactivation by brain synaptic peptidases. They account for the higher in vivo potency of [D-Tyr11]NT as compared with its in vitro potency. Finally, they explain, at least in part, the need to administer large doses of NT in the brain in order to observe neurobehavioral and neuropharmacological effects.
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Chen, Fuxiang; Su, Xingfen; Lin, Zhangya; Lin, Yuanxiang; Yu, Lianghong; Cai, Jiawei; Kang, Dezhi; Hu, Liwen
2017-01-01
Necroptosis is programmed cell death that has been recently proposed and reported to be involved in several neurologic diseases. However, the role of necroptosis in early brain injury after subarachnoid hemorrhage (SAH) is still unknown. The purpose of this study was to investigate whether necroptosis was involved in SAH-induced early brain injury, and to assess the possible neuroprotective effect of necrostatin-1 using an endovascular perforation rat model of SAH. Our results showed that the expression levels of necroptosis-related proteins including RIP1, RIP3 and MLKL in the basal cortex all increased at 3 hours after SAH ( P <0.05) and peaked at 48 hours after SAH ( P <0.05). However, they were greatly reduced after treatment with necrostatin-1 ( P <0.05). Concurrently, neurologic outcomes were significantly improved after necrostatin-1 treatment ( P <0.05). Furthermore, brain edema, blood-brain barrier disruption, necrotic cell death and neuroinflammation were also greatly inhibited after necrostatin-1 treatment. These results indicate that necroptosis is an important mechanism of cell death involved in the early brain injury after experimental SAH. Necrostatin-1 perhaps can serve as a promising neuroprotective agent for SAH treatment.
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Brain structure and verbal function across adulthood while controlling for cerebrovascular risks.
Sanfratello, L; Lundy, S L; Qualls, C; Knoefel, J E; Adair, J C; Caprihan, A; Stephen, J M; Aine, C J
2017-04-08
The development and decline of brain structure and function throughout adulthood is a complex issue, with cognitive aging trajectories influenced by a host of factors including cerebrovascular risk. Neuroimaging studies of age-related cognitive decline typically reveal a linear decrease in gray matter (GM) volume/density in frontal regions across adulthood. However, white matter (WM) tracts mature later than GM, particularly in regions necessary for executive functions and memory. Therefore, it was predicted that a middle-aged group (MC: 35-45 years) would perform best on a verbal working memory task and reveal greater regional WM integrity, compared with both young (YC: 18-25 years) and elder groups (EC: 60+ years). Diffusion tensor imaging (DTI) and magnetoencephalography (MEG) were obtained from 80 healthy participants. Objective measures of cerebrovascular risk and cognition were also obtained. As predicted, MC revealed best verbal working memory accuracy overall indicating some maturation of brain function between YC and MC. However, contrary to the prediction fractional anisotropy values (FA), a measure of WM integrity, were not greater in MC (i.e., there were no significant differences in FA between YC and MC but both groups showed greater FA than EC). An overall multivariate model for MEG ROIs showed greater peak amplitudes for MC and YC, compared with EC. Subclinical cerebrovascular risk factors (systolic blood pressure and blood glucose) were negatively associated with FA in frontal callosal, limbic, and thalamic radiation regions which correlated with executive dysfunction and slower processing speed, suggesting their contribution to age-related cognitive decline. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
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The effect of space radiation of the nervous system
NASA Astrophysics Data System (ADS)
Gauger, Grant E.; Tobias, Cornelius A.; Yang, Tracy; Whitney, Monroe
The long-term effects of irradiation by accelerated heavy ions on the structure and function of the nervous system have not been studied extensively. Although the adult brain is relatively resistant to low LET radiation, cellular studies indicate that individual heavy ions can produce serious membrane lesions and multiple chromatin breaks. Capillary hemorrhages may follow high LET particle irradiation of the developing brain as high RBE effects. Evidence has been accumulating that the glial system and blood-brain barrier (BBB) are relatively sensitive to injury by ionizing radiation. While DNA repair is active in neural systems, it may be assumed that a significant portion of this molecular process is misrepair. Since the expression of cell lethality usually requires cell division, and nerve cells have an extremely low rate of division, it is possible that some of the characteristic changes of premature aging may represent a delayed effect of chromatin misrepair in brain. Altered microcirculation, decreased local metabolism, entanglement and reduction in synaptic density, premature loss of neurons, myelin degeneration, and glial proliferation are late signs of such injuries. HZE particles are very efficient in producing carcinogenic cell transformation, reaching a peak for iron particles. The promotion of viral transformation is also efficient up to an energy transfer of approximately 300 keV/micron. The RBE for carcinogenesis in nerve tissues remains unknown. On the basis of available information concerning HZE particle flux in interplanetary space, only general estimates of the magnitude of the effects of long-term spaceflight on some nervous system parameters may be constructed.
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Zhao, Tengda; Cao, Miao; Niu, Haijing; Zuo, Xi-Nian; Evans, Alan; He, Yong; Dong, Qi; Shu, Ni
2015-10-01
Lifespan is a dynamic process with remarkable changes in brain structure and function. Previous neuroimaging studies have indicated age-related microstructural changes in specific white matter tracts during development and aging. However, the age-related alterations in the topological architecture of the white matter structural connectome across the human lifespan remain largely unknown. Here, a cohort of 113 healthy individuals (ages 9-85) with both diffusion and structural MRI acquisitions were examined. For each participant, the high-resolution white matter structural networks were constructed by deterministic fiber tractography among 1024 parcellation units and were quantified with graph theoretical analyses. The global network properties, including network strength, cost, topological efficiency, and robustness, followed an inverted U-shaped trajectory with a peak age around the third decade. The brain areas with the most significantly nonlinear changes were located in the prefrontal and temporal cortices. Different brain regions exhibited heterogeneous trajectories: the posterior cingulate and lateral temporal cortices displayed prolonged maturation/degeneration compared with the prefrontal cortices. Rich-club organization was evident across the lifespan, whereas hub integration decreased linearly with age, especially accompanied by the loss of frontal hubs and their connections. Additionally, age-related changes in structural connections were predominantly located within and between the prefrontal and temporal modules. Finally, based on the graph metrics of structural connectome, accurate predictions of individual age were obtained (r = 0.77). Together, the data indicated a dynamic topological organization of the brain structural connectome across human lifespan, which may provide possible structural substrates underlying functional and cognitive changes with age. © 2015 Wiley Periodicals, Inc.
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Ongoing compound field potentials from octopus brain are labile and vertebrate-like.
Bullock, T H
1984-05-01
Ongoing electrical activity was recorded from the brain of the virtually intact, semirestrained, unanesthetized octopus by semimicroelectrodes thrust through the cartilage into the optic, vertical or basal lobe. With flexible lead-in wires such electrodes were carried by and moved with the head without causing movement artifacts. Controls suggest that the activity reported comes from the brain; it is reversibly flattened by doses of urethane that do not embarrass respiration. Muscle potentials are only troublesome on occasion. Seen through a wideband filter, neuronal spikes are usually small or below noise level under these conditions; slow waves (1-70 Hz) dominate, with a maximum less than 25 Hz, usually less than 10 Hz and no consistent sharp peaks. The fall in power above ca. 25 Hz is usually slower than in the typical vertebrate EEG but the average power spectrum is much more like those of vertebrate brains than of cerebral ganglia of other invertebrates (insect, crustacean, gastropod). Variance among sample epochs is large, e.g. short spells may have relatively much more low frequency (less than 25 Hz) or more 'hashy' high frequency (greater than 50 Hz) energy; there may be runs of spikes. Fluctuation in the composition of ongoing activity is graphically shown by writing out in parallel the outputs of several narrow band (one octave) filters; this shows irregular low frequency waxing and waning of the amplitude in each band. The envelopes were computed and their peak power is around 1 Hz or lower; the waxing and waning in the several bands is sometimes strongly correlated, especially when the envelope amplitude is large and slow. Optic lobe activity tends usually to be faster, with more small spikey hash than in the vertical lobe. The described electrical activity of the brain is strikingly episodic; it is recorded during seconds or minutes separated by long intervals of nearly electrical silence (10-40 dB lower power; the difference larger at frequencies greater than 20 Hz). Active and quiet periods are usually not correlated with differences in visible behavior. Under my conditions the animal is usually not moving except for quiet ventilation and occasional local writhing of an arm. Potentials evoked by single flashes of light (0.2-1/sec) are conspicuous in the optic but not in the vertical lobe. They form a sequence of large, slow waves; the first peak may be at about 40 msec, others up to at least 400 msec.(ABSTRACT TRUNCATED AT 400 WORDS)
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Intrinsic connectivity in the human brain does not reveal networks for ‘basic’ emotions
Lindquist, Kristen A.; Dickerson, Bradford C.; Barrett, Lisa Feldman
2015-01-01
We tested two competing models for the brain basis of emotion, the basic emotion theory and the conceptual act theory of emotion, using resting-state functional connectivity magnetic resonance imaging (rs-fcMRI). The basic emotion view hypothesizes that anger, sadness, fear, disgust and happiness each arise from a brain network that is innate, anatomically constrained and homologous in other animals. The conceptual act theory of emotion hypothesizes that an instance of emotion is a brain state constructed from the interaction of domain-general, core systems within the brain such as the salience, default mode and frontoparietal control networks. Using peak coordinates derived from a meta-analysis of task-evoked emotion fMRI studies, we generated a set of whole-brain rs-fcMRI ‘discovery’ maps for each emotion category and examined the spatial overlap in their conjunctions. Instead of discovering a specific network for each emotion category, variance in the discovery maps was accounted for by the known domain-general network. Furthermore, the salience network is observed as part of every emotion category. These results indicate that specific networks for each emotion do not exist within the intrinsic architecture of the human brain and instead support the conceptual act theory of emotion. PMID:25680990
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ERIC Educational Resources Information Center
Spironelli, Chiara; Penolazzi, Barbara; Vio, Claudio; Angrilli, Alessandro
2010-01-01
Brain plasticity was investigated in 14 Italian children affected by developmental dyslexia after 6 months of phonological training. The means used to measure language reorganization was the recognition potential, an early wave, also called N150, elicited by automatic word recognition. This component peaks over the left temporo-occipital cortex…
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The Effects of Reinforcer Magnitude on Timing in Rats
ERIC Educational Resources Information Center
Ludvig, Elliot A.; Conover, Kent; Shizgal, Peter
2007-01-01
The relation between reinforcer magnitude and timing behavior was studied using a peak procedure. Four rats received multiple consecutive sessions with both low and high levels of brain stimulation reward (BSR). Rats paused longer and had later start times during sessions when their responses were reinforced with low-magnitude BSR. When estimated…
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Low-noise magnetoencephalography system cooled by a continuously operating reliquefier
NASA Astrophysics Data System (ADS)
Lee, Y. H.; Kwon, H.; Yu, K. K.; Kim, J. M.; Lee, S. K.; Kim, M.-Y.; Kim, K.
2017-08-01
We fabricated a low-noise magnetoencephalography (MEG) system based on a continuously operating reliquefier for cooling of low-temperature superconducting quantum interference device gradiometers. In order to reduce the vibration transmission, the gradiometers are mounted in the vacuum space of the helmet dewar with direct thermal contact with the liquid helium helmet. The reliquefier uses a 1.4 W pulse tube cryocooler with a remote motor, and a horizontal transfer tube with a downslope angle of 1°. The white noise of the system is 3.5 fTrms/√Hz (at 100 Hz). The vibration-induced peak at 1.4 Hz is 18 fTrms/√Hz averaged over the whole helmet array of 150 channels, which is the lowest among the reported values using reliquefier cooling and comparable to the noise peak cooled by conventional direct liquid helium cooling with axial gradiometers of the same baseline. The spontaneous brain activity signal showed nearly identical signal quality with the reliquefier turned on and off, and the reliquefier-based MEG system noise is well below the brain noise level.
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NASA Astrophysics Data System (ADS)
Pierro, Michele; Sassaroli, Angelo; Zheng, Feng; Fantini, Sergio
2011-02-01
We present a study of the relative phase of oscillations of cerebral oxy- and deoxy-hemoglobin concentrations in the low-frequency range, namely 0.04-0.12 Hz. We have characterized the potential contributions of noise to the measured phase distributions, and we have performed phase measurements on the brain of a human subject at rest, and on the brain of a human subject during stage I sleep. While phase distributions of pseudo hemodynamic oscillations generated from noise (obtained by applying to two independent sets of random numbers the same linear transformation that converts absorption coefficients at 690 and 830 nm into concentrations of oxy- and deoxy-hemoglobin) are peaked at 180º, those associated with real hemodynamic changes can be peaked around any value depending on the underlying physiology and hemodynamics. In particular, preliminary results reported here indicate a greater phase lead of deoxy-hemoglobin vs. oxy-hemoglobin low-frequency oscillations during stage I sleep (82º +/- 55º) than while the subject is awake (19º +/- 58º).
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Altschuler, E.L.; Dowla, F.U.
1998-11-24
The encephalolexianalyzer uses digital signal processing techniques on electroencephalograph (EEG) brain waves to determine whether or not someone is thinking about moving, e.g., tapping their fingers, or, alternatively, whether someone is actually moving, e.g., tapping their fingers, or at rest, i.e., not moving and not thinking of moving. The mu waves measured by a pair of electrodes placed over the motor cortex are signal processed to determine the power spectrum. At rest, the peak value of the power spectrum in the 8-13 Hz range is high, while when moving or thinking of moving, the peak value of the power spectrum in the 8-13 Hz range is low. This measured change in signal power spectrum is used to produce a control signal. The encephalolexianalyzer can be used to communicate either directly using Morse code, or via a cursor controlling a remote control; the encephalolexianalyzer can also be used to control other devices. The encephalolexianalyzer will be of great benefit to people with various handicaps and disabilities, and also has enormous commercial potential, as well as being an invaluable tool for studying the brain. 14 figs.
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Altschuler, Eric L.; Dowla, Farid U.
1998-01-01
The encephalolexianalyzer uses digital signal processing techniques on electroencephalograph (EEG) brain waves to determine whether or not someone is thinking about moving, e.g., tapping their fingers, or, alternatively, whether someone is actually moving, e.g., tapping their fingers, or at rest, i.e., not moving and not thinking of moving. The mu waves measured by a pair of electrodes placed over the motor cortex are signal processed to determine the power spectrum. At rest, the peak value of the power spectrum in the 8-13 Hz range is high, while when moving or thinking of moving, the peak value of the power spectrum in the 8-13 Hz range is low. This measured change in signal power spectrum is used to produce a control signal. The encephalolexianalyzer can be used to communicate either directly using Morse code, or via a cursor controlling a remote control; the encephalolexianalyzer can also be used to control other devices. The encephalolexianalyzer will be of great benefit to people with various handicaps and disabilities, and also has enormous commercial potential, as well as being an invaluable tool for studying the brain.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Moser, Virginia C., E-mail: Moser.ginger@epa.gov
Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., λ-cyhalothrin) as well as enriched active isomers (e.g., γ-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of λ- and γ-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5 h after oral gavagemore » dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for γ-cyhalothrin was lower than for λ-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the γ-isomer (1.29 mg/kg) compared to λ-cyhalothrin (2.65 mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of γ-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While γ-cyhalothrin was 2-fold more potent based on administered dose, the differences based on internal concentrations were less, with γ-cyhalothrin being 1.3- to 1.6-fold more potent than λ-cyhalothrin. These potency differences are consistent with the purity of the λ-isomer (approximately 43%) compared to the enriched isomer γ-cyhalothrin (approximately 98%). Thus, administered dose as well as differences in cyhalothrin isomers is a good predictor of behavioral effects. - Highlights: • Acute changes in locomotor activity were produced by λ- and γ-cyhalothrin. • γ-Cyhalothrin was about 2-fold more potent than λ-cyhalothrin. • Brain and plasma levels were tightly correlated across doses. • Activity changes correlated well with brain and plasma concentrations.« less
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NASA Astrophysics Data System (ADS)
Wang, Ruofan; Wang, Jiang; Li, Shunan; Yu, Haitao; Deng, Bin; Wei, Xile
2015-01-01
In this paper, we have combined experimental neurophysiologic recording and statistical analysis to investigate the nonlinear characteristic and the cognitive function of the brain. Spectrum and bispectrum analyses are proposed to extract multiple effective features of electroencephalograph (EEG) signals from Alzheimer's disease (AD) patients and further applied to distinguish AD patients from the normal controls. Spectral analysis based on autoregressive Burg method is first used to quantify the power distribution of EEG series in the frequency domain. Compared to the control group, the relative power spectral density of AD group is significantly higher in the theta frequency band, while lower in the alpha frequency bands. In addition, median frequency of spectrum is decreased, and spectral entropy ratio of these two frequency bands undergoes drastic changes at the P3 electrode in the central-parietal brain region, implying that the electrophysiological behavior in AD brain is much slower and less irregular. In order to explore the nonlinear high order information, bispectral analysis which measures the complexity of phase-coupling is further applied to P3 electrode in the whole frequency band. It is demonstrated that less bispectral peaks appear and the amplitudes of peaks fall, suggesting a decrease of non-Gaussianity and nonlinearity of EEG in ADs. Notably, the application of this method to five brain regions shows higher concentration of the weighted center of bispectrum and lower complexity reflecting phase-coupling by bispectral entropy. Based on spectrum and bispectrum analyses, six efficient features are extracted and then applied to discriminate AD from the normal in the five brain regions. The classification results indicate that all these features could differentiate AD patients from the normal controls with a maximum accuracy of 90.2%. Particularly, different brain regions are sensitive to different features. Moreover, the optimal combination of features obtained by discriminant analysis may improve the classification accuracy. These results demonstrate the great promise for scape EEG spectral and bispectral features as a potential effective method for detection of AD, which may facilitate our understanding of the pathological mechanism of the disease.
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Wang, Ruofan; Wang, Jiang; Li, Shunan; Yu, Haitao; Deng, Bin; Wei, Xile
2015-01-01
In this paper, we have combined experimental neurophysiologic recording and statistical analysis to investigate the nonlinear characteristic and the cognitive function of the brain. Spectrum and bispectrum analyses are proposed to extract multiple effective features of electroencephalograph (EEG) signals from Alzheimer's disease (AD) patients and further applied to distinguish AD patients from the normal controls. Spectral analysis based on autoregressive Burg method is first used to quantify the power distribution of EEG series in the frequency domain. Compared to the control group, the relative power spectral density of AD group is significantly higher in the theta frequency band, while lower in the alpha frequency bands. In addition, median frequency of spectrum is decreased, and spectral entropy ratio of these two frequency bands undergoes drastic changes at the P3 electrode in the central-parietal brain region, implying that the electrophysiological behavior in AD brain is much slower and less irregular. In order to explore the nonlinear high order information, bispectral analysis which measures the complexity of phase-coupling is further applied to P3 electrode in the whole frequency band. It is demonstrated that less bispectral peaks appear and the amplitudes of peaks fall, suggesting a decrease of non-Gaussianity and nonlinearity of EEG in ADs. Notably, the application of this method to five brain regions shows higher concentration of the weighted center of bispectrum and lower complexity reflecting phase-coupling by bispectral entropy. Based on spectrum and bispectrum analyses, six efficient features are extracted and then applied to discriminate AD from the normal in the five brain regions. The classification results indicate that all these features could differentiate AD patients from the normal controls with a maximum accuracy of 90.2%. Particularly, different brain regions are sensitive to different features. Moreover, the optimal combination of features obtained by discriminant analysis may improve the classification accuracy. These results demonstrate the great promise for scape EEG spectral and bispectral features as a potential effective method for detection of AD, which may facilitate our understanding of the pathological mechanism of the disease.
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LIMO EEG: a toolbox for hierarchical LInear MOdeling of ElectroEncephaloGraphic data.
Pernet, Cyril R; Chauveau, Nicolas; Gaspar, Carl; Rousselet, Guillaume A
2011-01-01
Magnetic- and electric-evoked brain responses have traditionally been analyzed by comparing the peaks or mean amplitudes of signals from selected channels and averaged across trials. More recently, tools have been developed to investigate single trial response variability (e.g., EEGLAB) and to test differences between averaged evoked responses over the entire scalp and time dimensions (e.g., SPM, Fieldtrip). LIMO EEG is a Matlab toolbox (EEGLAB compatible) to analyse evoked responses over all space and time dimensions, while accounting for single trial variability using a simple hierarchical linear modelling of the data. In addition, LIMO EEG provides robust parametric tests, therefore providing a new and complementary tool in the analysis of neural evoked responses.
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LIMO EEG: A Toolbox for Hierarchical LInear MOdeling of ElectroEncephaloGraphic Data
Pernet, Cyril R.; Chauveau, Nicolas; Gaspar, Carl; Rousselet, Guillaume A.
2011-01-01
Magnetic- and electric-evoked brain responses have traditionally been analyzed by comparing the peaks or mean amplitudes of signals from selected channels and averaged across trials. More recently, tools have been developed to investigate single trial response variability (e.g., EEGLAB) and to test differences between averaged evoked responses over the entire scalp and time dimensions (e.g., SPM, Fieldtrip). LIMO EEG is a Matlab toolbox (EEGLAB compatible) to analyse evoked responses over all space and time dimensions, while accounting for single trial variability using a simple hierarchical linear modelling of the data. In addition, LIMO EEG provides robust parametric tests, therefore providing a new and complementary tool in the analysis of neural evoked responses. PMID:21403915
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Manoli, Zoi; Parazzini, Marta; Ravazzani, Paolo; Samaras, Theodoros
2017-01-01
The lack of knowledge of the electric field distribution inside the brain of stroke patients receiving transcranial direct current stimulation (tDCS) calls for estimating it computationally. Moreover, the impact on this distribution of a novel clinical management approach which involves secondary motor areas (SMA) in stroke rehabilitation needs to be evaluated. Finally, the differences in the electric field distributions due to gender and age need to be investigated. This work presents the development of two different anatomical models (young adult female and elderly male) with an ischemic stroke region of spherical volume 10 cm 3 or 50 cm 3 , using numerical models of the Virtual Population (ViP). The stroke phase was considered as acute or chronic, resulting in different electrical properties of the area. Two different electrode montages were used - One over the lesion area and the contralateral supra-orbital region and the other over the SMA and the contralateral supra-orbital region. A quasi-electrostatic solver was used to numerically solve the Laplace equation with the finite-difference technique. Both the 99th percentile of the electric field intensity distribution ("E peak value") and the percentage of the tissue volumes with electric field intensity over 50% and 70% of the E peak value were assessed inside the target areas of the primary motor cortex (M1) and the SMA, as well as in other brain tissues (hypothalamus and cerebellum). In the acute phase of an ischemic stroke, the normalized electric field intensity distributions do not differ noticeably compared to those in the brain of a healthy person (mean square difference < 2%). The difference becomes larger (up to 4.5%) for the chronic phase of a large ischemic lesion. Moreover, the maximum values of the induced electric field in the tissues in the SMA are almost equal for both electrode montages. The peak values of the electric field distribution ("E peak values") in cerebellum and hypothalamus for both electrode montages are rather small but different from those of healthy patients. The largest difference of 21% decrease with respect to a healthy subject was noticed in the elder adult model with a large chronic lesion. The comparison of the different electrode montages shows that the use of a stimulating electrode over the affected area creates larger values of the electric field in M1, by up to 26% for a small chronic lesion in the young female model. On the contrary, the montage does not affect considerably (change less than 8%) the E peak values in the SMA. This implies that for exciting M1, the M1-Fp2 montage should be favored. The presence and the phase of an ischemic stroke lesion, as well as the configuration of electrode montages affect the distribution and the maximum value of the electric field induced in tissues. Moreover, patients whom seem to benefit most from tDCS are those in the chronic phase of an ischemic stroke, since contrasts in the tissue conductivity result in a higher electric field induced around the lesion volume, which could stimulate the remaining healthy tissue in the area. © 2016 American Association of Physicists in Medicine.
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Systematic profiling of spatiotemporal tissue and cellular stiffness in the developing brain.
Iwashita, Misato; Kataoka, Noriyuki; Toida, Kazunori; Kosodo, Yoichi
2014-10-01
Accumulating evidence implicates the significance of the physical properties of the niche in influencing the behavior, growth and differentiation of stem cells. Among the physical properties, extracellular stiffness has been shown to have direct effects on fate determination in several cell types in vitro. However, little evidence exists concerning whether shifts in stiffness occur in vivo during tissue development. To address this question, we present a systematic strategy to evaluate the shift in stiffness in a developing tissue using the mouse embryonic cerebral cortex as an experimental model. We combined atomic force microscopy measurements of tissue and cellular stiffness with immunostaining of specific markers of neural differentiation to correlate the value of stiffness with the characteristic features of tissues and cells in the developing brain. We found that the stiffness of the ventricular and subventricular zones increases gradually during development. Furthermore, a peak in tissue stiffness appeared in the intermediate zone at E16.5. The stiffness of the cortical plate showed an initial increase but decreased at E18.5, although the cellular stiffness of neurons monotonically increased in association with the maturation of the microtubule cytoskeleton. These results indicate that tissue stiffness cannot be solely determined by the stiffness of the cells that constitute the tissue. Taken together, our method profiles the stiffness of living tissue and cells with defined characteristics and can therefore be utilized to further understand the role of stiffness as a physical factor that determines cell fate during the formation of the cerebral cortex and other tissues. © 2014. Published by The Company of Biologists Ltd.
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Burkhart, C S; Dell-Kuster, S; Siegemund, M; Pargger, H; Marsch, S; Strebel, S P; Steiner, L A
2014-07-01
Data regarding immunomodulatory effects of parenteral n-3 fatty acids in sepsis are conflicting. In this study, the effect of administration of parenteral n-3 fatty acids on markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients was investigated. Fifty patients with sepsis were randomized to receive either 2 ml/kg/day of a lipid emulsion containing highly refined fish oil (equivalent to n-3 fatty acids 0.12 mg/kg/day) during 7 days after admission to the intensive care unit or standard treatment. Markers of brain injury and inflammatory mediators were measured on days 1, 2, 3 and 7. Assessment for sepsis-associated delirium was performed daily. The primary outcome was the difference in S-100β from baseline to peak level between both the intervention and the control group, compared by t-test. Changes of all markers over time were explored in both groups, fitting a generalized estimating equations model. Mean difference in change of S-100β from baseline to peak level was 0.34 (95% CI: -0.18-0.85) between the intervention and control group, respectively (P = 0.19). We found no difference in plasma levels of S-100β, neuron-specific enolase, interleukin (IL)-6, IL-8, IL-10, and C-reactive protein between groups over time. Incidence of sepsis-associated delirium was 75% in the intervention and 71% in the control groups (risk difference 4%, 95% CI -24-31%, P = 0.796). Administration of n-3 fatty acids did not affect markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
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Ickenstein, G W; Valaikiene, J; Koch, H; Hau, P; Erban, P; Schlachetzki, F
2008-04-01
The aim of this study was to evaluate brain perfusion differences in patients with high grade gliomas after partial tumor resection and irradiation/chemotherapy between tumor and non-tumor hemisphere by transcranial perfusion sonography (TPS) employing a contrast burst imaging (CBI) technique. Six patients with glioblastoma (WHO Grade IV) in the temporoparietal region within the defined axial diencephalic scanning plane were examined by TPS during follow-up. All subjects had an adequate acoustic temporal bone window. Transtemporal insonation on brain tumor and non-tumor hemisphere was performed with a bolus-injection of sulphur hexafluoride-based contrast agent (10 mg i.v., 5mg/ml--SonoVue, Bracco, Altana, Switzerland). Recorded images were analysed off-line by Quanticon Software (3D-Echotech, Munich, Germany) and time intensity curve parameters [area under the curve (AUC, dB s), peak intensity (PI, dB), time to peak (TTP, s)] in five regions of interest (ROI) [thalamus anterior, thalamus posterior, nucleus lentiformis, white matter, whole hemisphere] were evaluated. Statistical analyses were performed. Perfusion differences between brain tumor and non-tumor hemispheres were detected with contrast burst imaging (CBI) technique with a significantly greater mean AUC (5343.69 dB s vs. 4625.04 dB s, p<0.028) and a significantly prolonged TTP (32.72 s vs. 28.91 s, p<0.046) in the tumor hemisphere. Within our study population, TTP and AUC seem to be the most robust parameters for the evaluation of cerebral perfusion differences assessed by transcranial perfusion sonography with CBI technique. We hypothesize that these results correlate with microvascular changes due to treatment regimens, such as microvessel necrosis after irradiation and chemotherapy. Above that, TPS may be of value for the long-term follow-up of brain tumor therapy concept.
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The time-course of cortico-limbic neural responses to air hunger.
Binks, Andrew P; Evans, Karleyton C; Reed, Jeffrey D; Moosavi, Shakeeb H; Banzett, Robert B
2014-12-01
Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (∼ 45 mm Hg). Subjects rated dyspnea (air hunger) via visual analog scale (VAS). Tidal volume (V(T)) was alternated every 90 s between high VT (0.96 ± 0.23 L) that provided respiratory comfort (12 ± 6% full scale) and low V(T) (0.48 ± 0.08 L) which evoked air hunger (56 ± 11% full scale). BOLD signal was extracted from a priori brain regions and combined with VAS data to determine air hunger related neural time-course. Air hunger onset was associated with BOLD signal increases that followed two distinct temporal profiles within sub-regions of the anterior insula, anterior cingulate and prefrontal cortices (cortico-limbic circuitry): (1) fast, BOLD signal peak <30s and (2) slow, BOLD signal peak >40s. BOLD signal during air hunger offset followed fast and slow temporal profiles symmetrical, but inverse (signal decreases) to the time-courses of air hunger onset. We conclude that differential cortico-limbic circuit elements have unique contributions to dyspnea sensation over time. We suggest that previously unidentified sub-regions are responsible for either the acute awareness or maintenance of dyspnea. These data enhance interpretation of previous studies and inform hypotheses for future dyspnea research. Copyright © 2014 Elsevier B.V. All rights reserved.
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Hasler, Brant P; Forbes, Erika E; Franzen, Peter L
2014-10-30
Human and animal studies indicate that reward function is modulated by the circadian clock that governs our daily sleep/wake rhythm. For example, a robust circadian rhythm exists in positive affect, which is lower in the morning hours and peaks in the afternoon. A handful of functional neuroimaging studies suggest that systematic diurnal variation exists in brain activity related to other functions, but no published human studies have examined daily variation in the neural processing of reward. In the present study, we attempt to advance this literature by using functional neuroimaging methods to examine time-of-day changes in the responsivity of the reward circuit. Using a within-person design and a functional magnetic resonance imaging (fMRI) monetary reward task, we compared morning and afternoon reward-related brain activation in a sample of healthy young adults within 24h. Region of interest analyses focused on the striatum, and we hypothesized greater reward activation in the afternoon, concordant with the circadian peak in positive affect. Results were consistent with our hypothesis. In addition, we counterbalanced the order of morning and afternoon scans in order to explore the short-term stability of the neural response. Whole-brain analyses showed a markedly higher reactivity to reward throughout the brain in the first scan relative to the second scan, consistent with habituation to the monetary reward stimuli. However, these effects did not appear to explain the time-of-day findings. In summary, we report the first preliminary evidence of circadian variation in the neural processing of reward. These findings have both methodological and theoretical implications. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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Saroka, Kevin S.; Vares, David E.; Persinger, Michael A.
2016-01-01
In 1954 and 1960 Koenig and his colleagues described the remarkable similarities of spectral power density profiles and patterns between the earth-ionosphere resonance and human brain activity which also share magnitudes for both electric field (mV/m) and magnetic field (pT) components. In 2006 Pobachenko and colleagues reported real time coherence between variations in the Schumann and brain activity spectra within the 6–16 Hz band for a small sample. We examined the ratios of the average potential differences (~3 μV) obtained by whole brain quantitative electroencephalography (QEEG) between rostral-caudal and left-right (hemispheric) comparisons of 238 measurements from 184 individuals over a 3.5 year period. Spectral densities for the rostral-caudal axis revealed a powerful peak at 10.25 Hz while the left-right peak was 1.95 Hz with beat-differences of ~7.5 to 8 Hz. When global cerebral measures were employed, the first (7–8 Hz), second (13–14 Hz) and third (19–20 Hz) harmonics of the Schumann resonances were discernable in averaged QEEG profiles in some but not all participants. The intensity of the endogenous Schumann resonance was related to the ‘best-of-fitness’ of the traditional 4-class microstate model. Additional measurements demonstrated real-time coherence for durations approximating microstates in spectral power density variations between Schumann frequencies measured in Sudbury, Canada and Cumiana, Italy with the QEEGs of local subjects. Our results confirm the measurements reported by earlier researchers that demonstrated unexpected similarities in the spectral patterns and strengths of electromagnetic fields generated by the human brain and the earth-ionospheric cavity. PMID:26785376
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Saroka, Kevin S; Vares, David E; Persinger, Michael A
2016-01-01
In 1954 and 1960 Koenig and his colleagues described the remarkable similarities of spectral power density profiles and patterns between the earth-ionosphere resonance and human brain activity which also share magnitudes for both electric field (mV/m) and magnetic field (pT) components. In 2006 Pobachenko and colleagues reported real time coherence between variations in the Schumann and brain activity spectra within the 6-16 Hz band for a small sample. We examined the ratios of the average potential differences (~3 μV) obtained by whole brain quantitative electroencephalography (QEEG) between rostral-caudal and left-right (hemispheric) comparisons of 238 measurements from 184 individuals over a 3.5 year period. Spectral densities for the rostral-caudal axis revealed a powerful peak at 10.25 Hz while the left-right peak was 1.95 Hz with beat-differences of ~7.5 to 8 Hz. When global cerebral measures were employed, the first (7-8 Hz), second (13-14 Hz) and third (19-20 Hz) harmonics of the Schumann resonances were discernable in averaged QEEG profiles in some but not all participants. The intensity of the endogenous Schumann resonance was related to the 'best-of-fitness' of the traditional 4-class microstate model. Additional measurements demonstrated real-time coherence for durations approximating microstates in spectral power density variations between Schumann frequencies measured in Sudbury, Canada and Cumiana, Italy with the QEEGs of local subjects. Our results confirm the measurements reported by earlier researchers that demonstrated unexpected similarities in the spectral patterns and strengths of electromagnetic fields generated by the human brain and the earth-ionospheric cavity.
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Maitre, Nathalie L; Stark, Ann R; McCoy Menser, Carrie C; Chorna, Olena D; France, Daniel J; Key, Alexandra F; Wilkens, Ken; Moore-Clingenpeel, Melissa; Wilkes, Don M; Bruehl, Stephen
2017-09-01
Newborns requiring hospitalisation frequently undergo painful procedures. Prevention of pain in infants is of prime concern because of adverse associations with physiological and neurological development. However, pain mitigation is currently guided by behavioural observation assessments that have not been validated against direct evidence of pain processing in the brain. The aim of this study was to determine whether cry presence or amplitude is a valid indicator of pain processing in newborns. Prospective observational cohort. Newborn nursery. Healthy infants born at >37 weeks and <42 weeks gestation. We prospectively studied newborn cortical responses to light touch, cold and heel stick, and the amplitude of associated infant vocalisations using our previously published paradigms of time-locked electroencephalogram (EEG) with simultaneous audio recordings. Latencies of cortical peak responses to each of the three stimuli type were significantly different from each other. Of 54 infants, 13 (24%), 19 (35%) and 35 (65%) had cries in response to light touch, cold and heel stick, respectively. Cry in response to non-painful stimuli did not predict cry in response to heel stick. All infants with EEG data had measurable pain responses to heel stick, whether they cried or not. There was no association between presence or amplitude of cries and cortical nociceptive amplitudes. In newborns with distinct brain responses to light touch, cold and pain, cry presence or amplitude characteristics do not provide adequate behavioural markers of pain signalling in the brain. New bedside assessments of newborn pain may need to be developed using brain-based methodologies as benchmarks in order to provide optimal pain mitigation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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Soares, Edilene S; Stávale, Leila M; Mendonça, Monique C P; Coope, Andressa; Cruz-Höfling, Maria Alice da
2016-11-23
We have previously demonstrated that Phoneutria nigriventer venom (PNV) causes blood-brain barrier (BBB) breakdown, swelling of astrocytes end-feet and fluid permeation into brain interstitium in rats. Caveolae and water channels respond to BBB alterations by co-participation in shear stress response and edema formation/resolution. Herein, we showed post-natal developmental-related changes of two BBB-associated transporter proteins: the endothelial caveolin-1 (Cav-1), the major scaffolding protein from caveolae frame, and the astroglial aquaporin-4 (AQP4), the main water channel protein expressed in astrocytic peri-vascular end-feet processes, in the hippocampus of rats intraperitoneally-administered PNV. Western blotting protein levels; immunohistochemistry (IHC) protein distribution in CA1, CA2, and CA3 subfields; and gene expression by Real Time-Polymerase Chain Reaction (qPCR) were assessed in post-natal Day 14 (P14) and 8-10-week-old rats over critical periods of envenomation. The intensity and duration of the toxic manifestations indicate P14 neonate rats more vulnerable to PNV than adults. Histologically, the capillaries of P14 and 8-10-week-old rats treated with PNV showed perivascular edema, while controls did not. The intensity of the toxic manifestations in P14 decreases temporally (2 > 5 > 24 h), while inversely the expression of AQP4 and Cav-1 peaked at 24 h when clinically PNV-treated animals do not differ from saline controls. IHC of AQP4 revealed that hippocampal CA1 showed the least expression at 2 h when toxic manifestation was maximal. Subfield IHC quantification revealed that in P14 rats Cav-1 peaked at 24 h when toxic manifestations were absent, whereas in 8-10-week-old rats Cav-1 peaked at 2 h when toxic signs were highest, and progressively attenuated such increases until 24 h, remaining though significantly above baseline. Considering astrocyte-endothelial physical and functional interactions, we hypothesize that age-related modulations of AQP4 and Cav-1 might be linked both to changes in functional properties of astrocytes during post-natal development and in the BBB breakdown induced by the venom of P. nigriventer .
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An animal-to-human scaling law for blast-induced traumatic brain injury risk assessment.
Jean, Aurélie; Nyein, Michelle K; Zheng, James Q; Moore, David F; Joannopoulos, John D; Radovitzky, Raúl
2014-10-28
Despite recent efforts to understand blast effects on the human brain, there are still no widely accepted injury criteria for humans. Recent animal studies have resulted in important advances in the understanding of brain injury due to intense dynamic loads. However, the applicability of animal brain injury results to humans remains uncertain. Here, we use advanced computational models to derive a scaling law relating blast wave intensity to the mechanical response of brain tissue across species. Detailed simulations of blast effects on the brain are conducted for different mammals using image-based biofidelic models. The intensity of the stress waves computed for different external blast conditions is compared across species. It is found that mass scaling, which successfully estimates blast tolerance of the thorax, fails to capture the brain mechanical response to blast across mammals. Instead, we show that an appropriate scaling variable must account for the mass of protective tissues relative to the brain, as well as their acoustic impedance. Peak stresses transmitted to the brain tissue by the blast are then shown to be a power function of the scaling parameter for a range of blast conditions relevant to TBI. In particular, it is found that human brain vulnerability to blast is higher than for any other mammalian species, which is in distinct contrast to previously proposed scaling laws based on body or brain mass. An application of the scaling law to recent experiments on rabbits furnishes the first physics-based injury estimate for blast-induced TBI in humans.
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Kuboyama, Kazuya; Fujikawa, Akihiro; Suzuki, Ryoko; Tanga, Naomi; Noda, Masaharu
2016-08-26
Protein-tyrosine phosphatase receptor type Z (PTPRZ) is predominantly expressed in the developing brain as a CS proteoglycan. PTPRZ has long (PTPRZ-A) and short type (PTPRZ-B) receptor forms by alternative splicing. The extracellular CS moiety of PTPRZ is required for high-affinity binding to inhibitory ligands, such as pleiotrophin (PTN), midkine, and interleukin-34; however, its functional significance in regulating PTPRZ activity remains obscure. We herein found that protein expression of CS-modified PTPRZ-A began earlier, peaking at approximately postnatal days 5-10 (P5-P10), and then that of PTN peaked at P10 at the developmental stage corresponding to myelination onset in the mouse brain. Ptn-deficient mice consistently showed a later onset of the expression of myelin basic protein, a major component of the myelin sheath, than wild-type mice. Upon ligand application, PTPRZ-A/B in cultured oligodendrocyte precursor cells exhibited punctate localization on the cell surface instead of diffuse distribution, causing the inactivation of PTPRZ and oligodendrocyte differentiation. The same effect was observed with the removal of CS chains with chondroitinase ABC but not polyclonal antibodies against the extracellular domain of PTPRZ. These results indicate that the negatively charged CS moiety prevents PTPRZ from spontaneously clustering and that the positively charged ligand PTN induces PTPRZ clustering, potentially by neutralizing electrostatic repulsion between CS chains. Taken altogether, these data indicate that PTN-PTPRZ-A signaling controls the timing of oligodendrocyte precursor cell differentiation in vivo, in which the CS moiety of PTPRZ receptors maintains them in a monomeric active state until its ligand binding. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
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Oeur, R Anna; Karton, Clara; Post, Andrew; Rousseau, Philippe; Hoshizaki, T Blaine; Marshall, Shawn; Brien, Susan E; Smith, Aynsley; Cusimano, Michael D; Gilchrist, Michael D
2015-08-01
Concussions typically resolve within several days, but in a few cases the symptoms last for a month or longer and are termed persistent postconcussive symptoms (PPCS). These persisting symptoms may also be associated with more serious brain trauma similar to subdural hematoma (SDH). The objective of this study was to investigate the head dynamic and brain tissue responses of injury reconstructions resulting in concussion, PPCS, and SDH. Reconstruction cases were obtained from sports medicine clinics and hospitals. All subjects received a direct blow to the head resulting in symptoms. Those symptoms that resolved in 9 days or fewer were defined as concussions (n = 3). Those with symptoms lasting longer than 18 months were defined as PPCS (n = 3), and 3 patients presented with SDHs (n = 3). A Hybrid III headform was used in reconstruction to obtain linear and rotational accelerations of the head. These dynamic response data were then input into the University College Dublin Brain Trauma Model to calculate maximum principal strain and von Mises stress. A Kruskal-Wallis test followed by Tukey post hoc tests were used to compare head dynamic and brain tissue responses between injury groups. Statistical significance was set at p < 0.05. A significant difference was identified for peak resultant linear and rotational acceleration between injury groups. Post hoc analyses revealed the SDH group had higher linear and rotational acceleration responses (316 g and 23,181 rad/sec(2), respectively) than the concussion group (149 g and 8111 rad/sec(2), respectively; p < 0.05). No significant differences were found between groups for either brain tissue measures of maximum principal strain or von Mises stress. The reconstruction of accidents resulting in a concussion with transient symptoms (low severity) and SDHs revealed a positive relationship between an increase in head dynamic response and the risk for more serious brain injury. This type of relationship was not found for brain tissue stress and strain results derived by finite element analysis. Future research should be undertaken using a larger sample size to confirm these initial findings. Understanding the relationship between the head dynamic and brain tissue response and the nature of the injury provides important information for developing strategies for injury prevention.
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McDonnell, Liam A; Heeren, Ron M A; de Lange, Robert P J; Fletcher, Ian W
2006-09-01
To expand the role of high spatial resolution secondary ion mass spectrometry (SIMS) in biological studies, numerous developments have been reported in recent years for enhancing the molecular ion yield of high mass molecules. These include both surface modification, including matrix-enhanced SIMS and metal-assisted SIMS, and polyatomic primary ions. Using rat brain tissue sections and a bismuth primary ion gun able to produce atomic and polyatomic primary ions, we report here how the sensitivity enhancements provided by these developments are additive. Combined surface modification and polyatomic primary ions provided approximately 15.8 times more signal than using atomic primary ions on the raw sample, whereas surface modification and polyatomic primary ions yield approximately 3.8 and approximately 8.4 times more signal. This higher sensitivity is used to generate chemically specific images of higher mass biomolecules using a single molecular ion peak.
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Spatial-temporal-spectral EEG patterns of BOLD functional network connectivity dynamics
NASA Astrophysics Data System (ADS)
Lamoš, Martin; Mareček, Radek; Slavíček, Tomáš; Mikl, Michal; Rektor, Ivan; Jan, Jiří
2018-06-01
Objective. Growing interest in the examination of large-scale brain network functional connectivity dynamics is accompanied by an effort to find the electrophysiological correlates. The commonly used constraints applied to spatial and spectral domains during electroencephalogram (EEG) data analysis may leave part of the neural activity unrecognized. We propose an approach that blindly reveals multimodal EEG spectral patterns that are related to the dynamics of the BOLD functional network connectivity. Approach. The blind decomposition of EEG spectrogram by parallel factor analysis has been shown to be a useful technique for uncovering patterns of neural activity. The simultaneously acquired BOLD fMRI data were decomposed by independent component analysis. Dynamic functional connectivity was computed on the component’s time series using a sliding window correlation, and between-network connectivity states were then defined based on the values of the correlation coefficients. ANOVA tests were performed to assess the relationships between the dynamics of between-network connectivity states and the fluctuations of EEG spectral patterns. Main results. We found three patterns related to the dynamics of between-network connectivity states. The first pattern has dominant peaks in the alpha, beta, and gamma bands and is related to the dynamics between the auditory, sensorimotor, and attentional networks. The second pattern, with dominant peaks in the theta and low alpha bands, is related to the visual and default mode network. The third pattern, also with peaks in the theta and low alpha bands, is related to the auditory and frontal network. Significance. Our previous findings revealed a relationship between EEG spectral pattern fluctuations and the hemodynamics of large-scale brain networks. In this study, we suggest that the relationship also exists at the level of functional connectivity dynamics among large-scale brain networks when no standard spatial and spectral constraints are applied on the EEG data.
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Design and fabrication of a flexible substrate microelectrode array for brain machine interfaces.
Patrick, Erin; Ordonez, Matthew; Alba, Nicolas; Sanchez, Justin C; Nishida, Toshikazu
2006-01-01
We report a neural microelectrode array design that leverages the recording properties of conventional microwire electrode arrays with the additional features of precise control of the electrode geometries. Using microfabrication techniques, a neural probe array is fabricated that possesses a flexible polyimide-based cable. The performance of the design was tested with electrochemical impedance spectroscopy and in vivo studies. The gold-plated electrode site has an impedance value of 0.9 M Omega at 1 kHz. Acute neural recording provided high neuronal yields, peak-to-peak amplitudes (as high as 100 microV), and signal-to-noise ratios (27 dB).
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Brain-water diffusion coefficients reflect the severity of inherited prion disease
Hyare, H.; Wroe, S.; Siddique, D.; Webb, T.; Fox, N. C.; Stevens, J.; Collinge, J.; Yousry, T.; Thornton, J. S.
2010-01-01
Objective: Inherited prion diseases are progressive neurodegenerative conditions, characterized by cerebral spongiosis, gliosis, and neuronal loss, caused by mutations within the prion protein (PRNP) gene. We wished to assess the potential of diffusion-weighted MRI as a biomarker of disease severity in inherited prion diseases. Methods: Twenty-five subjects (mean age 45.2 years) with a known PRNP mutation including 19 symptomatic patients, 6 gene-positive asymptomatic subjects, and 7 controls (mean age 54.1 years) underwent conventional and diffusion-weighted MRI. An index of normalized brain volume (NBV) and region of interest (ROI) mean apparent diffusion coefficient (ADC) for the head of caudate, putamen, and pulvinar nuclei were recorded. ADC histograms were computed for whole brain (WB) and gray matter (GM) tissue fractions. Clinical assessment utilized standardized clinical scores. Mann-Whitney U test and regression analyses were performed. Results: Symptomatic patients exhibited an increased WB mean ADC (p = 0.006) and GM mean ADC (p = 0.024) compared to controls. Decreased NBV and increased mean ADC measures significantly correlated with clinical measures of disease severity. Using a stepwise multivariate regression procedure, GM mean ADC was an independent predictor of Clinician's Dementia Rating score (p = 0.001), Barthel Index of activities of daily living (p = 0.001), and Rankin disability score (p = 0.019). Conclusions: Brain volume loss in inherited prion diseases is accompanied by increased cerebral apparent diffusion coefficient (ADC), correlating with increased disease severity. The association between gray matter ADC and clinical neurologic status suggests this measure may prove a useful biomarker of disease activity in inherited prion diseases. GLOSSARY ADAS-Cog = Alzheimer's Disease Assessment Scale–Cognitive subscale; ADC = apparent diffusion coefficient; ADL = Barthel Activities of Daily Living scale; BET = brain extraction tool; BPRS = Brief Psychiatric Rating Scale; BSE = bovine spongiform encephalopathy; CDR = Clinician's Dementia Rating Scale; CGIS = Clinician's Global Impression of Disease; CI = confidence interval; DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; FOV = field of view; GM = gray matter; LC = left head of caudate; LP = left putamen; LPu = left pulvinar; MMSE = Mini-Mental State Examination; NBV = normalized brain volume; PH = peak height; PL = peak location; RC = right head of caudate; RP = right putamen; RPu = right pulvinar; ROI = region of interest; sCJD = sporadic Creutzfeldt-Jakob disease; TE = echo time; TI = inversion time; TR = repetition time; vCJD = variant Creutzfeldt-Jakob disease; WB = whole brain; WM = white matter. PMID:20177119
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Transcranial Alternating Current Stimulation Attenuates Neuronal Adaptation.
Kar, Kohitij; Duijnhouwer, Jacob; Krekelberg, Bart
2017-03-01
We previously showed that brief application of 2 mA (peak-to-peak) transcranial currents alternating at 10 Hz significantly reduces motion adaptation in humans. This is but one of many behavioral studies showing that weak currents applied to the scalp modulate neural processing. Transcranial stimulation has been shown to improve perception, learning, and a range of clinical symptoms. Few studies, however, have measured the neural consequences of transcranial current stimulation. We capitalized on the strong link between motion perception and neural activity in the middle temporal (MT) area of the macaque monkey to study the neural mechanisms that underlie the behavioral consequences of transcranial alternating current stimulation. First, we observed that 2 mA currents generated substantial intracranial fields, which were much stronger in the stimulated hemisphere (0.12 V/m) than on the opposite side of the brain (0.03 V/m). Second, we found that brief application of transcranial alternating current stimulation at 10 Hz reduced spike-frequency adaptation of MT neurons and led to a broadband increase in the power spectrum of local field potentials. Together, these findings provide a direct demonstration that weak electric fields applied to the scalp significantly affect neural processing in the primate brain and that this includes a hitherto unknown mechanism that attenuates sensory adaptation. SIGNIFICANCE STATEMENT Transcranial stimulation has been claimed to improve perception, learning, and a range of clinical symptoms. Little is known, however, how transcranial current stimulation generates such effects, and the search for better stimulation protocols proceeds largely by trial and error. We investigated, for the first time, the neural consequences of stimulation in the monkey brain. We found that even brief application of alternating current stimulation reduced the effects of adaptation on single-neuron firing rates and local field potentials; this mechanistic insight explains previous behavioral findings and suggests a novel way to modulate neural information processing using transcranial currents. In addition, by developing an animal model to help understand transcranial stimulation, this study will aid the rational design of stimulation protocols for the treatment of mental illnesses, and the improvement of perception and learning. Copyright © 2017 the authors 0270-6474/17/372325-11$15.00/0.
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Automated data processing of { 1H-decoupled} 13C MR spectra acquired from human brain in vivo
NASA Astrophysics Data System (ADS)
Shic, Frederick; Ross, Brian
2003-06-01
In clinical 13C infusion studies, broadband excitation of 200 ppm of the human brain yields 13C MR spectra with a time resolution of 2-5 min and generates up to 2000 metabolite peaks over 2 h. We describe a fast, automated, observer-independent technique for processing { 1H-decoupled} 13C spectra. Quantified 13C spectroscopic signals, before and after the administration of [1- 13C]glucose and/or [1- 13C]acetate in human subjects are determined. Stepwise improvements of data processing are illustrated by examples of normal and pathological results. Variation in analysis of individual 13C resonances ranged between 2 and 14%. Using this method it is possible to reliably identify subtle metabolic effects of brain disease including Alzheimer's disease and epilepsy.
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Reward, salience, and attentional networks are activated by religious experience in devout Mormons
Ferguson, Michael A.; Nielsen, Jared A.; King, Jace B.; Dai, Li; Giangrasso, Danielle M.; Holman, Rachel; Korenberg, Julie R.; Anderson, Jeffrey S.
2017-01-01
High-level cognitive and emotional experience arises from brain activity, but the specific brain substrates for religious and spiritual euphoria remain unclear. We demonstrate using functional magnetic resonance imaging scans in 19 devout Mormons that a recognizable feeling central to their devotional practice was reproducibly associated with activation in nucleus accumbens, ventromedial prefrontal cortex, and frontal attentional regions. Nucleus accumbens activation preceded peak spiritual feelings by 1–3 s and was replicated in four separate tasks. Attentional activation in the anterior cingulate and frontal eye fields was greater in the right hemisphere. The association of abstract ideas and brain reward circuitry may interact with frontal attentional and emotive salience processing, suggesting a mechanism whereby doctrinal concepts may come to be intrinsically rewarding and motivate behavior in religious individuals. PMID:27834117
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Rawashdeh, Oliver; Hudson, Randall L.; Stepien, Iwona; Dubocovich, Margarita L.
2016-01-01
Ramelteon, an MT1/MT2 melatonin receptor agonist, is used for the treatment of sleep-onset insomnia and circadian sleep disorders. Ramelteon phase shifts circadian rhythms in rodents and humans when given at the end of the subjective day; however, its efficacy at other circadian times is not known. Here, the authors determined in C3H/ HeN mice the maximal circadian sensitivity for ramelteon in vivo on the onset of circadian running-wheel activity rhythms, and in vitro on the peak of circadian rhythm of neuronal firing in suprachiasmatic nucleus (SCN) brain slices. The phase response curve (PRC) for ramelteon (90 μg/mouse, subcutaneous [sc]) on circadian wheel-activity rhythms shows maximal sensitivity during the late mid to end of the subjective day, between CT8 and CT12 (phase advance), and late subjective night and early subjective day, between CT20 and CT2 (phase delay), using a 3-day-pulse treatment regimen in C3H/HeN mice. The PRC for ramelteon resembles that for melatonin in C3H/ HeN mice, showing the same magnitude of maximal shifts at CT10 and CT2, except that the range of sensitivity for ramelteon (CT8–CT12) during the subjective day is broader. Furthermore, in SCN brain slices in vitro, ramelteon (10 pM) administered at CT10 phase advances (5.6 ± 0.29 h, n = 3) and at CT2 phase delays (−3.2 ± 0.12 h, n = 6) the peak of circadian rhythm of neuronal firing, with the shifts being significantly larger than those induced by melatonin (10 pM) at the same circadian times (CT10: 2.7 ± 0.15 h, n = 4, p < .05; CT2: −1.13 ± 0.08 h, n = 6, p < .001, respectively). The phase shifts induced by both melatonin and ramelteon in the SCN brain slice at either CT10 or CT2 corresponded with the period of sensitivity observed in vivo. In conclusion, melatonin and ramelteon showed identical periods of circadian sensitivity at CT10 (advance) and CT2 (delay) to shift the onset of circadian activity rhythms in vivo and the peak of SCN neuronal firing rhythms in vitro. PMID:21182402
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Vesicular glutamate transporters VGLUT1 and VGLUT2 in the developing mouse barrel cortex.
Liguz-Lecznar, M; Skangiel-Kramska, J
2007-04-01
Three vesicular glutamate transporters have been identified in mammals. Two of them, VGLUT1 and VGLUT2, define the glutamatergic phenotype and their distribution in the brain is almost complementary. In the present study we examined the distribution and expression levels of these two VGLUTs during postnatal development of the mouse barrel cortex. We also investigated changes in the localization of VGLUT1 and VGLUT2 within particular compartments of the barrel field (barrels/septa) during its development. We found differences in the time course of developmental expression, with VGLUT1 peaking around P14, while VGLUT2 increased gradually until adulthood. Over the examined period (P3 - adult) both transporters had stronger expression in the barrel interiors, and in this compartment VGLUT2 dominated, whereas in the inter-barrel septa VGLUT1 dominated over VGLUT2. Furthermore, we found that some nerve terminals in the barrel cortex coexpressed both transporters until adulthood. Colocalization was observed within the barrels, but not within the septa.
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Cantagallo, Anna; Di Russo, Francesco; Favilla, Marco; Zoccolotti, Pierluigi
2015-04-15
The capability of quickly (as soon as possible) producing fast uncorrected and accurate isometric force impulses was examined to assess the motor efficiency of patients with moderate to severe traumatic brain injury (TBI) and good motor recovery at a clinical evaluation. Twenty male right-handed patients with moderate to severe TBI and 24 age-matched healthy male right-handed controls participated in the study. The experimental task required subjects to aim brief and uncorrected isometric force impulses to targets visually presented along with subjects' force displays. Both TBI patients and controls were able to produce force impulses whose mean peak amplitudes varied proportionally to the target load with no detectable group difference. Patients with TBI, however, were slower than controls in initiating their responses (reaction times [RTs] were longer by 125 msec) and were also slower during the execution of their motor responses, reaching the peak forces requested 23 msec later than controls (time to peak force: 35% delay). Further, their mean dF/dt (35 kg/sec) was slower than that of controls (53 kg/sec), again indicating a 34% impairment with respect to controls. Overall, patients with TBI showed accurate but delayed and slower isometric force impulses. Thus, an evaluation taking into account also response time features is more effective in picking up motor impairments than the standard clinical scales focusing on accuracy of movement only.
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Red-shifted aequorin-based bioluminescent reporters for in vivo imaging of Ca2 signaling.
Curie, Thomas; Rogers, Kelly L; Colasante, Cesare; Brûlet, Philippe
2007-01-01
Real-time visualization of calcium (Ca(2+)) dynamics in the whole animal will enable important advances in understanding the complexities of cellular function. The genetically encoded bioluminescent Ca(2+) reporter green fluorescent protein-aequorin (GA) allows noninvasive detection of intracellular Ca(2+) signaling in freely moving mice. However, the emission spectrum of GA is not optimal for detection of activity from deep tissues in the whole animal. To overcome this limitation, two new reporter genes were constructed by fusing the yellow fluorescent protein (Venus) and the monomeric red fluorescent protein (mRFP1) to aequorin. Transfer of aequorin chemiluminescence energy to Venus (VA) is highly efficient and produces a 58 nm red shift in the peak emission spectrum of aequorin. This substantially improves photon transmission through tissue, such as the skin and thoracic cage. Although the Ca(2+)-induced bioluminescence spectrum of mRFP1-aequorin (RA) is similar to that of aequorin, there is also a small peak above 600 nm corresponding to the peak emission of mRFP1. Small amounts of energy transfer between aequorin and mRFP1 yield an emission spectrum with the highest percentage of total light above 600 nm compared with GA and VA. Accordingly, RA is also detected with higher sensitivity from brain areas. VA and RA will therefore improve optical access to Ca(2+) signaling events in deeper tissues, such as the heart and brain, and offer insight for engineering new hybrid molecules.
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Individual Alpha Peak Frequency Predicts 10 Hz Flicker Effects on Selective Attention.
Gulbinaite, Rasa; van Viegen, Tara; Wieling, Martijn; Cohen, Michael X; VanRullen, Rufin
2017-10-18
Rhythmic visual stimulation ("flicker") is primarily used to "tag" processing of low-level visual and high-level cognitive phenomena. However, preliminary evidence suggests that flicker may also entrain endogenous brain oscillations, thereby modulating cognitive processes supported by those brain rhythms. Here we tested the interaction between 10 Hz flicker and endogenous alpha-band (∼10 Hz) oscillations during a selective visuospatial attention task. We recorded EEG from human participants (both genders) while they performed a modified Eriksen flanker task in which distractors and targets flickered within (10 Hz) or outside (7.5 or 15 Hz) the alpha band. By using a combination of EEG source separation, time-frequency, and single-trial linear mixed-effects modeling, we demonstrate that 10 Hz flicker interfered with stimulus processing more on incongruent than congruent trials (high vs low selective attention demands). Crucially, the effect of 10 Hz flicker on task performance was predicted by the distance between 10 Hz and individual alpha peak frequency (estimated during the task). Finally, the flicker effect on task performance was more strongly predicted by EEG flicker responses during stimulus processing than during preparation for the upcoming stimulus, suggesting that 10 Hz flicker interfered more with reactive than proactive selective attention. These findings are consistent with our hypothesis that visual flicker entrained endogenous alpha-band networks, which in turn impaired task performance. Our findings also provide novel evidence for frequency-dependent exogenous modulation of cognition that is determined by the correspondence between the exogenous flicker frequency and the endogenous brain rhythms. SIGNIFICANCE STATEMENT Here we provide novel evidence that the interaction between exogenous rhythmic visual stimulation and endogenous brain rhythms can have frequency-specific behavioral effects. We show that alpha-band (10 Hz) flicker impairs stimulus processing in a selective attention task when the stimulus flicker rate matches individual alpha peak frequency. The effect of sensory flicker on task performance was stronger when selective attention demands were high, and was stronger during stimulus processing and response selection compared with the prestimulus anticipatory period. These findings provide novel evidence that frequency-specific sensory flicker affects online attentional processing, and also demonstrate that the correspondence between exogenous and endogenous rhythms is an overlooked prerequisite when testing for frequency-specific cognitive effects of flicker. Copyright © 2017 the authors 0270-6474/17/3710173-12$15.00/0.
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Post, Andrew; Oeur, Anna; Walsh, Evan; Hoshizaki, Blaine; Gilchrist, Michael D
2014-01-01
American football reports high incidences of head injuries, in particular, concussion. Research has described concussion as primarily a rotation dominant injury affecting the diffuse areas of brain tissue. Current standards do not measure how helmets manage rotational acceleration or how acceleration loading curves influence brain deformation from an impact and thus are missing important information in terms of how concussions occur. The purpose of this study was to investigate a proposed three-dimensional impact protocol for use in evaluating football helmets. The dynamic responses resulting from centric and non-centric impact conditions were examined to ascertain the influence they have on brain deformations in different functional regions of the brain that are linked to concussive symptoms. A centric and non-centric protocol was used to impact an American football helmet; the resulting dynamic response data was used in conjunction with a three-dimensional finite element analysis of the human brain to calculate brain tissue deformation. The direction of impact created unique loading conditions, resulting in peaks in different regions of the brain associated with concussive symptoms. The linear and rotational accelerations were not predictive of the brain deformation metrics used in this study. In conclusion, the test protocol used in this study revealed that impact conditions influences the region of loading in functional regions of brain tissue that are associated with the symptoms of concussion. The protocol also demonstrated that using brain deformation metrics may be more appropriate when evaluating risk of concussion than using dynamic response data alone.
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Wijetunge, Chalini D; Saeed, Isaam; Boughton, Berin A; Spraggins, Jeffrey M; Caprioli, Richard M; Bacic, Antony; Roessner, Ute; Halgamuge, Saman K
2015-10-01
Matrix Assisted Laser Desorption Ionization-Imaging Mass Spectrometry (MALDI-IMS) in 'omics' data acquisition generates detailed information about the spatial distribution of molecules in a given biological sample. Various data processing methods have been developed for exploring the resultant high volume data. However, most of these methods process data in the spectral domain and do not make the most of the important spatial information available through this technology. Therefore, we propose a novel streamlined data analysis pipeline specifically developed for MALDI-IMS data utilizing significant spatial information for identifying hidden significant molecular distribution patterns in these complex datasets. The proposed unsupervised algorithm uses Sliding Window Normalization (SWN) and a new spatial distribution based peak picking method developed based on Gray level Co-Occurrence (GCO) matrices followed by clustering of biomolecules. We also use gist descriptors and an improved version of GCO matrices to extract features from molecular images and minimum medoid distance to automatically estimate the number of possible groups. We evaluated our algorithm using a new MALDI-IMS metabolomics dataset of a plant (Eucalypt) leaf. The algorithm revealed hidden significant molecular distribution patterns in the dataset, which the current Component Analysis and Segmentation Map based approaches failed to extract. We further demonstrate the performance of our peak picking method over other traditional approaches by using a publicly available MALDI-IMS proteomics dataset of a rat brain. Although SWN did not show any significant improvement as compared with using no normalization, the visual assessment showed an improvement as compared to using the median normalization. The source code and sample data are freely available at http://exims.sourceforge.net/. awgcdw@student.unimelb.edu.au or chalini_w@live.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Xia, Xiaohua; Huo, Weiran; Wan, Ruyan; Zhang, Linxia; Xia, Xiaopei; Chang, Zhongjie
2017-01-01
Sox3 is a single-exon gene located on the X chromosome in most vertebrates. It belongs to the SoxB1 subfamily, which is part of the larger Sox family. Previous studies have revealed that Sox3 is expressed in many fish species. However, how Sox3 influences the development of Misgurnus anguillicaudatus remains unknown. In this study, a Sox3 homologue, termed MaSox3, was cloned from the brain of M. anguillicaudatus using homology-based cloning and the rapid amplification of cDNA ends method. Sequence analysis reveals that MaSox3 encodes a hydrophilic protein, which contains a characteristic HMG-box DNA-binding domain of 79 amino acids, and shares high homology with Sox3 in other species. Additionally, quantitative real-time reverse transcription PCR and in situ hybridization showed that MaSox3 is consistently expressed during embryogenesis, with peak expression during the neurula stage and broad expression in the central nervous system. Moreover, tissue distribution analyses have revealed that MaSox3 is abundant in the adult brain, the particle cell layer, and the gonad. Additionally, its expression is observed in primary spermatocyte cells, primary oocytes and previtellogenic oocyte cells. Taken together, all of these results suggest that the expression of the MaSox3 gene is highly conserved during vertebrate evolution and involved in a wide range of developmental processes including embryogenesis, neurogenesis and gonad development.
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Pereira, Glauber B; Meng, Fanxue; Kockara, Neriman T; Yang, Baoli; Wight, Patricia A
2013-02-01
Myelin proteolipid protein gene (Plp1) expression is temporally regulated in brain, which peaks during the active myelination period of CNS development. Previous studies with Plp1-lacZ transgenic mice demonstrated that (mouse) Plp1 intron 1 DNA is required for high levels of expression in oligodendrocytes. Deletion-transfection analysis revealed the intron contains a single positive regulatory element operative in the N20.1 oligodendroglial cell line, which was named ASE (antisilencer/enhancer) based on its functional properties in these cells. To investigate the role of the ASE in vivo, the element was deleted from the native gene in mouse using a Cre/lox strategy. Although removal of the ASE from Plp1-lacZ constructs profoundly decreased expression in transfected oligodendroglial cell lines (N20.1 and Oli-neu), the element was dispensable to achieve normal levels of Plp1 gene expression in mouse during development (except perhaps at postnatal day 15) and throughout the remyelination period following cuprizone-induced (acute) demyelination. Thus, it is possible that the ASE is non-functional in vivo, or that loss of the ASE from the native gene in mouse can be compensated for by the presence of other regulatory elements within the Plp1 gene. © 2012 International Society for Neurochemistry.
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Diehl, Hanna C; Beine, Birte; Elm, Julian; Trede, Dennis; Ahrens, Maike; Eisenacher, Martin; Marcus, Katrin; Meyer, Helmut E; Henkel, Corinna
2015-03-01
Mass spectrometry imaging (MSI) has become a powerful and successful tool in the context of biomarker detection especially in recent years. This emerging technique is based on the combination of histological information of a tissue and its corresponding spatial resolved mass spectrometric information. The identification of differentially expressed protein peaks between samples is still the method's bottleneck. Therefore, peptide MSI compared to protein MSI is closer to the final goal of identification since peptides are easier to measure than proteins. Nevertheless, the processing of peptide imaging samples is challenging due to experimental complexity. To address this issue, a method development study for peptide MSI using cryoconserved and formalin-fixed paraffin-embedded (FFPE) rat brain tissue is provided. Different digestion times, matrices, and proteases were tested to define an optimal workflow for peptide MSI. All practical experiments were done in triplicates and analyzed by the SCiLS Lab software, using structures derived from myelin basic protein (MBP) peaks, principal component analysis (PCA) and probabilistic latent semantic analysis (pLSA) to rate the experiments' quality. Blinded experimental evaluation in case of defining countable structures in the datasets was performed by three individuals. Such an extensive method development for peptide matrix-assisted laser desorption/ionization (MALDI) imaging experiments has not been performed so far, and the resulting problems and consequences were analyzed and discussed.
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Gosselin, Marie-Christine; Kühn, Sven; Crespo-Valero, Pedro; Cherubini, Emilio; Zefferer, Marcel; Christ, Andreas; Kuster, Niels
2011-09-01
The maximum spatial peak exposure of each commercial mobile phone determined in compliance with the relevant safety and product standards is publicly available. However, this information is not sufficient for epidemiological studies aiming to correlate the use of mobile phones with specific cancers or to behavioral alterations, as the dominant location of the exposure may be anywhere in the head between the chin to above the ear, depending on the phone design. The objective of this study was to develop a methodology to determine tissue-specific exposure by expanding the post-processing of the measured surface or volume scans using standardized compliance testing equipment, that is, specific absorption rate (SAR) scanners. The transformation matrix was developed using the results from generic dipoles to evaluate the relation between the SAR in many brain regions of the Virtual Family anatomical phantoms and in virtual brain regions mapped onto the homogeneous SAM head. A set of transformation factors was derived to correlate the SAR induced in the SAM head to the SAR in the anatomical heads. The evaluation included the uncertainty associated with each factor, arising from the anatomical differences between the phantoms (typically less than 6 dB (4×)). The applicability of these factors was validated by performing simulations of four head models exposed to four realistic mobile phone models. The new methodology enables the reliable determination of the maximum and averaged exposure of specific tissues and functional brain regions to mobile phones when combined with mobile phone power control data, and therefore greatly strengthens epidemiological evaluations and improves information for the consumer. Copyright © 2011 Wiley-Liss, Inc.
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Lightweight, compact, and high-performance 3T MR system for imaging the brain and extremities.
Foo, Thomas K F; Laskaris, Evangelos; Vermilyea, Mark; Xu, Minfeng; Thompson, Paul; Conte, Gene; Van Epps, Christopher; Immer, Christopher; Lee, Seung-Kyun; Tan, Ek T; Graziani, Dominic; Mathieu, Jean-Baptise; Hardy, Christopher J; Schenck, John F; Fiveland, Eric; Stautner, Wolfgang; Ricci, Justin; Piel, Joseph; Park, Keith; Hua, Yihe; Bai, Ye; Kagan, Alex; Stanley, David; Weavers, Paul T; Gray, Erin; Shu, Yunhong; Frick, Matthew A; Campeau, Norbert G; Trzasko, Joshua; Huston, John; Bernstein, Matt A
2018-03-13
To build and evaluate a small-footprint, lightweight, high-performance 3T MRI scanner for advanced brain imaging with image quality that is equal to or better than conventional whole-body clinical 3T MRI scanners, while achieving substantial reductions in installation costs. A conduction-cooled magnet was developed that uses less than 12 liters of liquid helium in a gas-charged sealed system, and standard NbTi wire, and weighs approximately 2000 kg. A 42-cm inner-diameter gradient coil with asymmetric transverse axes was developed to provide patient access for head and extremity exams, while minimizing magnet-gradient interactions that adversely affect image quality. The gradient coil was designed to achieve simultaneous operation of 80-mT/m peak gradient amplitude at a slew rate of 700 T/m/s on each gradient axis using readily available 1-MVA gradient drivers. In a comparison of anatomical imaging in 16 patients using T 2 -weighted 3D fluid-attenuated inversion recovery (FLAIR) between the compact 3T and whole-body 3T, image quality was assessed as equivalent to or better across several metrics. The ability to fully use a high slew rate of 700 T/m/s simultaneously with 80-mT/m maximum gradient amplitude resulted in improvements in image quality across EPI, DWI, and anatomical imaging of the brain. The compact 3T MRI system has been in continuous operation at the Mayo Clinic since March 2016. To date, over 200 patient studies have been completed, including 96 comparison studies with a clinical 3T whole-body MRI. The increased gradient performance has reliably resulted in consistently improved image quality. © 2018 International Society for Magnetic Resonance in Medicine.
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Xu, Wencheng; Shekhar, Sameer; Abbaspour-Tamijani, Abbas; Towe, Bruce C.; Miranda, Félix A.; Chae, Junseok
2011-01-01
The ability to safely monitor neuropotentials is essential in establishing methods to study the brain. Current research focuses on the wireless telemetry aspect of implantable sensors in order to make these devices ubiquitous and safe. Chronic implants necessitate superior reliability and durability of the integrated electronics. The power consumption of implanted electronics must also be limited to within several milliwatts to microwatts to minimize heat trauma in the human body. In order to address these severe requirements, we developed an entirely passive and wireless microsystem for recording neuropotentials. An external interrogator supplies a fundamental microwave carrier to the microsystem. The microsystem comprises varactors that perform nonlinear mixing of neuropotential and fundamental carrier signals. The varactors generate third-order mixing products that are wirelessly backscattered to the external interrogator where the original neuropotential signals are recovered. Performance of the neuro-recording microsystem was demonstrated by wireless recording of emulated and in vivo neuropotentials. The obtained results were wireless recovery of neuropotentials as low as approximately 500 microvolts peak-to-peak (μVpp) with a bandwidth of 10 Hz to 3 kHz (for emulated signals) and with 128 epoch signal averaging of repetitive signals (for in vivo signals). PMID:22267898
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Naganawa, Shinji; Satake, Hiroko; Iwano, Shingo; Kawai, Hisashi; Kubota, Seiji; Komada, Tomohiro; Kawamura, Minako; Sakurai, Yasuo; Fukatsu, Hiroshi
2008-02-01
The BLADE and PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) techniques have been proposed to reduce the effect of head motion. Preliminary results have shown that BLADE also reduces pulsation artifacts from venous sinuses. The purpose of this study was to compare T1-weighted FLAIR acquired with BLADE (T1W-FLAIR BLADE) and T1-weighted spin-echo (T1W-SE) for the detection of contrast enhancement in a phantom and in patients with suspected brain lesions and to compare the degree of flow-related artifacts in the patients. A phantom filled with diluted Gd-DTPA was scanned in addition to 27 patients. In the phantom study, the peak contrast-to-noise ratio of T1W-FLAIR BLADE was larger than that of T1W-SE, and the position of the peak was shifted to a lower concentration. In patients, the degree of flow-related artifacts was significantly higher in T1W-SE. Among the 27 patients, 9 had metastatic tumor, and 18 did not. On a patient-by-patient basis, the sensitivity and specificity for the detection of metastatic lesions on axial T1W-SE were 100% and 55.6% respectively, while on axial T1W-FLAIR BLADE they were 100% and 100%. T1W-FLAIR BLADE seems to be capable of replacing T1W-SE, at least for axial post-contrast imaging to detect brain metastases.
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Key role of T cell defects in age-related vulnerability to West Nile virus.
Brien, James D; Uhrlaub, Jennifer L; Hirsch, Alec; Wiley, Clayton A; Nikolich-Zugich, Janko
2009-11-23
West Nile virus (WNV) infection causes a life-threatening meningoencephalitis that becomes increasingly more prevalent over the age of 50 and is 40-50x more prevalent in people over the age of 70, compared with adults under the age of 40. In a mouse model of age-related vulnerability to WNV, we demonstrate that death correlates with increased viral titers in the brain and that this loss of virus control with age was the result of defects in the CD4 and CD8 T cell response against WNV. Specific age-related defects in T cell responses against dominant WNV epitopes were detected at the level of cytokine and lytic granule production, each of which are essential for resistance against WNV, and in the ability to generate multifunctional anti-WNV effector T cells, which are believed to be critical for robust antiviral immunity. In contrast, at the peak of the response, old and adult T cells exhibited superimposable peptide sensitivity. Most importantly, although the adult CD4 or CD8 T cells readily protected immunodeficient mice upon adoptive transfer, old T cells of either subset were unable to provide WNV-specific protection. Consistent with a profound qualitative and quantitative defect in T cell immunity, old brains contained at least 12x fewer total effector CD8 T cells compared with adult mice at the peak of brain infection. These findings identify potential targets for immunomodulation and treatment to combat lethal WNV infection in the elderly.
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NASA Astrophysics Data System (ADS)
Sousa, Fernanda; Mandal, Subhra; Garrovo, Chiara; Astolfo, Alberto; Bonifacio, Alois; Latawiec, Diane; Menk, Ralf Hendrik; Arfelli, Fulvia; Huewel, Sabine; Legname, Giuseppe; Galla, Hans-Joachim; Krol, Silke
2010-12-01
In the present study, the in vivo distribution of polyelectrolyte multilayer coated gold nanoparticles is shown, starting from the living animal down to cellular level. The coating was designed with functional moieties to serve as a potential nano drug for prion disease. With near infrared time-domain imaging we followed the biodistribution in mice up to 7 days after intravenous injection of the nanoparticles. The peak concentration in the head of mice was detected between 19 and 24 h. The precise particle distribution in the brain was studied ex vivo by X-ray microtomography, confocal laser and fluorescence microscopy. We found that the particles mainly accumulate in the hippocampus, thalamus, hypothalamus, and the cerebral cortex.In the present study, the in vivo distribution of polyelectrolyte multilayer coated gold nanoparticles is shown, starting from the living animal down to cellular level. The coating was designed with functional moieties to serve as a potential nano drug for prion disease. With near infrared time-domain imaging we followed the biodistribution in mice up to 7 days after intravenous injection of the nanoparticles. The peak concentration in the head of mice was detected between 19 and 24 h. The precise particle distribution in the brain was studied ex vivo by X-ray microtomography, confocal laser and fluorescence microscopy. We found that the particles mainly accumulate in the hippocampus, thalamus, hypothalamus, and the cerebral cortex. Electronic supplementary information (ESI) available: Fig. S1-S6. See DOI: 10.1039/c0nr00345j
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Proton spectroscopy in the narcoleptic syndrome. Is there evidence of a brainstem lesion?
Ellis, C M; Simmons, A; Lemmens, G; Williams, S C; Parkes, J D
1998-02-01
There is controversy regarding the relationship of structural or biochemical brainstem lesions to "idiopathic" narcolepsy. Most cases of the narcoleptic syndrome are considered to be idiopathic because no structural lesion is detectable, although some cases of secondary narcolepsy are known to be associated with no structural brainstem lesions. Using proton spectroscopy, we determined levels of ventral pontine metabolite pools in 12 normal subjects and 12 subjects with idiopathic narcolepsy. REM sleep is generated in ventral pontine areas. Proton spectroscopy was used to study levels of N-acetyl aspartate (NAA) as a marker of cell mass, creatine and phosphocreatine (Cr + PCr), and choline (Cho). The intensity of the peaks, as determined by the area under the peak (AUP), was measured. The AUP correlates with the quantity of chemical present. In this study, the ratios of NAA to Cr + PCr were similar in normal subjects and in narcoleptic subjects with idiopathic narcolepsy. No differences in measured metabolic ratio were observed in subjects who slept during the scan procedure compared with those who remained awake. Subjects with "symptomatic" narcolepsy accompanied by an obvious structural brain lesion were not studied. Proton spectroscopy of the brain initiates a new kind of neurochemistry, allowing the noninvasive study of metabolic pools in the living human brain without the use of any kind of tracer or radioactive molecule. In this study, there was no evidence of cell loss in the ventral pontine areas of subjects with the narcoleptic syndrome.
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Zhao, Dongxing; Meyer-Gerspach, Anne Christin; Deloose, Eveline; Iven, Julie; Weltens, Nathalie; Depoortere, Inge; O'daly, Owen; Tack, Jan; Van Oudenhove, Lukas
2018-01-29
The motilin agonist, erythromycin, induces gastric phase III of the migrating motor complex, which in turn generates hunger peaks. To identify the brain mechanisms underlying these orexigenic effects, 14 healthy women participated in a randomized, placebo-controlled crossover study. Functional magnetic resonance brain images were acquired for 50 minutes interprandially. Intravenous infusion of erythromycin (40 mg) or saline started 10 minutes after the start of scanning. Blood samples (for glucose and hormone levels) and hunger ratings were collected at fixed timepoints. Thirteen volunteers completed the study, without any adverse events. Brain regions involved in homeostatic and hedonic control of appetite and food intake responded to erythromycin, including pregenual anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, amygdala, caudate, pallidum and putamen bilaterally, right accumbens, hypothalamus, and midbrain. Octanoylated ghrelin levels decreased, whereas both glucose and insulin increased after erythromycin. Hunger were higher after erythromycin, and these differences covaried with the brain response in most of the abovementioned regions. The motilin agonist erythromycin increases hunger by modulating neurocircuitry related to homeostatic and hedonic control of appetite and feeding. These results confirm recent behavioural findings identifying motilin as a key orexigenic hormone in humans, and identify the brain mechanisms underlying its effect.
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Li, F; Zhang, Y; Ma, S L
2016-12-01
To observe the changes of expression of α-synuclein （α-syn） and neuronal apoptosis in brain cortex of acute alcoholism rats and to explore the mechanism of the damage caused by ethanol to the neurons. The model of acute alcoholism rat was established by 50% alcohol gavage. The α-syn and caspase-3 were detected by immunohistochemical staining and imaging analysis at 1 h, 3 h, 6 h and 12 h after acute alcoholism. The number of positive cell and mean of optical density were detected and the trend change was analyzed. The variance analysis and t -test were also performed. The number of α-syn positive cell and average optical density in brain cortex of acute alcoholism rat increased significantly and peaked at 6 hour with a following slight decrease at 12 h, but still higher than the groups at 1 h and 3 h. Within 12 hours after poisoning, the number of caspase-3 positive cell and average optical density in brain cortex of rats gradually increased. The abnormal aggregation of α-syn caused by brain edema and hypoxia may participate the early stage of neuronal apoptosis in brain cortex after acute alcoholism. Copyright© by the Editorial Department of Journal of Forensic Medicine
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NASA Astrophysics Data System (ADS)
Hatano, Ben; Matsumoto, Yoshihisa; Otani, Naoki; Saitoh, Daizoh; Tokuno, Shinichi; Satoh, Yasushi; Nawashiro, Hiroshi; Matsushita, Yoshitaro; Sato, Shunichi
2011-03-01
The detailed mechanism of blast-induced traumatic brain injury (bTBI) has not been revealed yet. Thus, reliable laboratory animal models for bTBI are needed to investigate the possible diagnosis and treatment for bTBI. In this study, we used laser-induced shock wave (LISW) to induce TBI in rats and investigated the histopathological similarities to actual bTBI. After craniotomy, the rat brain was exposed to a single shot of LISW with a diameter of 3 mm at various laser fluences. At 24 h after LISW exposure, perfusion fixation was performed and the extracted brain was sectioned; the sections were stained with hematoxylin-eosin. Evans blue (EB) staining was also used to evaluate disruption of the blood brain barrier. At certain laser fluence levels, neural cell injury and hemorrhagic lesions were observed in the cortex and subcortical region. However, injury was limited in the tissue region that interacted with the LISW. The severity of injury increased with increasing laser fluence and hence peak pressure of the LISW. Fluorescence originating from EB was diffusively observed in the injuries at high fluence levels. Due to the grade and spatial controllability of injuries and the histological observations similar to those in actual bTBI, brain injuries caused by LISWs would be useful models to study bTBI.
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ICA model order selection of task co-activation networks.
Ray, Kimberly L; McKay, D Reese; Fox, Peter M; Riedel, Michael C; Uecker, Angela M; Beckmann, Christian F; Smith, Stephen M; Fox, Peter T; Laird, Angela R
2013-01-01
Independent component analysis (ICA) has become a widely used method for extracting functional networks in the brain during rest and task. Historically, preferred ICA dimensionality has widely varied within the neuroimaging community, but typically varies between 20 and 100 components. This can be problematic when comparing results across multiple studies because of the impact ICA dimensionality has on the topology of its resultant components. Recent studies have demonstrated that ICA can be applied to peak activation coordinates archived in a large neuroimaging database (i.e., BrainMap Database) to yield whole-brain task-based co-activation networks. A strength of applying ICA to BrainMap data is that the vast amount of metadata in BrainMap can be used to quantitatively assess tasks and cognitive processes contributing to each component. In this study, we investigated the effect of model order on the distribution of functional properties across networks as a method for identifying the most informative decompositions of BrainMap-based ICA components. Our findings suggest dimensionality of 20 for low model order ICA to examine large-scale brain networks, and dimensionality of 70 to provide insight into how large-scale networks fractionate into sub-networks. We also provide a functional and organizational assessment of visual, motor, emotion, and interoceptive task co-activation networks as they fractionate from low to high model-orders.
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ICA model order selection of task co-activation networks
Ray, Kimberly L.; McKay, D. Reese; Fox, Peter M.; Riedel, Michael C.; Uecker, Angela M.; Beckmann, Christian F.; Smith, Stephen M.; Fox, Peter T.; Laird, Angela R.
2013-01-01
Independent component analysis (ICA) has become a widely used method for extracting functional networks in the brain during rest and task. Historically, preferred ICA dimensionality has widely varied within the neuroimaging community, but typically varies between 20 and 100 components. This can be problematic when comparing results across multiple studies because of the impact ICA dimensionality has on the topology of its resultant components. Recent studies have demonstrated that ICA can be applied to peak activation coordinates archived in a large neuroimaging database (i.e., BrainMap Database) to yield whole-brain task-based co-activation networks. A strength of applying ICA to BrainMap data is that the vast amount of metadata in BrainMap can be used to quantitatively assess tasks and cognitive processes contributing to each component. In this study, we investigated the effect of model order on the distribution of functional properties across networks as a method for identifying the most informative decompositions of BrainMap-based ICA components. Our findings suggest dimensionality of 20 for low model order ICA to examine large-scale brain networks, and dimensionality of 70 to provide insight into how large-scale networks fractionate into sub-networks. We also provide a functional and organizational assessment of visual, motor, emotion, and interoceptive task co-activation networks as they fractionate from low to high model-orders. PMID:24339802
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BrainMap VBM: An environment for structural meta-analysis.
Vanasse, Thomas J; Fox, P Mickle; Barron, Daniel S; Robertson, Michaela; Eickhoff, Simon B; Lancaster, Jack L; Fox, Peter T
2018-05-02
The BrainMap database is a community resource that curates peer-reviewed, coordinate-based human neuroimaging literature. By pairing the results of neuroimaging studies with their relevant meta-data, BrainMap facilitates coordinate-based meta-analysis (CBMA) of the neuroimaging literature en masse or at the level of experimental paradigm, clinical disease, or anatomic location. Initially dedicated to the functional, task-activation literature, BrainMap is now expanding to include voxel-based morphometry (VBM) studies in a separate sector, titled: BrainMap VBM. VBM is a whole-brain, voxel-wise method that measures significant structural differences between or within groups which are reported as standardized, peak x-y-z coordinates. Here we describe BrainMap VBM, including the meta-data structure, current data volume, and automated reverse inference functions (region-to-disease profile) of this new community resource. CBMA offers a robust methodology for retaining true-positive and excluding false-positive findings across studies in the VBM literature. As with BrainMap's functional database, BrainMap VBM may be synthesized en masse or at the level of clinical disease or anatomic location. As a use-case scenario for BrainMap VBM, we illustrate a trans-diagnostic data-mining procedure wherein we explore the underlying network structure of 2,002 experiments representing over 53,000 subjects through independent components analysis (ICA). To reduce data-redundancy effects inherent to any database, we demonstrate two data-filtering approaches that proved helpful to ICA. Finally, we apply hierarchical clustering analysis (HCA) to measure network- and disease-specificity. This procedure distinguished psychiatric from neurological diseases. We invite the neuroscientific community to further exploit BrainMap VBM with other modeling approaches. © 2018 Wiley Periodicals, Inc.
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Diagnosis and treatment of urea cycle disorder in Japan.
Nakamura, Kimitoshi; Kido, Jun; Mitsubuchi, Hiroshi; Endo, Fumio
2014-08-01
Urea cycle disorder (UCD) is an inborn error of the metabolic pathway producing urea from ammonia, which occurs primarily in the liver. Decreased excretion of nitrogen in the urea cycle due to deficiency of carbamoyl phosphate synthase I (CPSI), ornithine transcarbamylase (OTC), argininosuccinate synthase (ASS), argininosuccinate lyase (ASL), and N-acetyl glutamate synthase (NAGS) causes hyperammonemia. We examined the clinical manifestations, treatment, and prognosis of 177 patients with UCD from January 1999 to March 2009 in Japan. Compared with a previous study conducted in Japan, a larger number of patients survived without mental retardation, even when the peak blood ammonia was >360 μmol/L. In those with peak blood ammonia >360 μmol/L, an indicator of poor prognosis, the frequency of convulsions, mental retardation, brain abnormality on magnetic resonance imaging, hemodialysis, liver transplantation, and intake of non-protein formulas was significantly higher than in those with peak blood ammonia <360 μmol/L. In this article, we have reported the current state of UCD to evaluate prognosis and its relationship with peak blood ammonia and hemodialysis. © 2014 Japan Pediatric Society.
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Joshi, Elizabeth M; Need, Anne; Schaus, John; Chen, Zhaogen; Benesh, Dana; Mitch, Charles; Morton, Stuart; Raub, Thomas J; Phebus, Lee; Barth, Vanessa
2014-12-17
Positron emission tomography (PET) imaging has become a useful noninvasive technique to explore molecular biology within living systems; however, the utility of this method is limited by the availability of suitable radiotracers to probe specific targets and disease biology. Methods to identify potential areas of improvement in the ability to predict small molecule performance as tracers prior to radiolabeling would speed the discovery of novel tracers. In this retrospective analysis, we characterized the brain penetration or peak SUV (standardized uptake value), binding potential (BP), and brain exposure kinetics across a series of known, nonradiolabeled PET ligands using in vivo LC-MS/MS (liquid chromatography coupled to mass spectrometry) and correlated these parameters with the reported PET ligand performance in nonhuman primates and humans available in the literature. The PET tracers studied included those reported to label G protein-coupled receptors (GPCRs), intracellular enzymes, and transporters. Additionally, data for each tracer was obtained from a mouse brain uptake assay (MBUA), previously published, where blood-brain barrier (BBB) penetration and clearance parameters were assessed and compared against similar data collected on a broad compound set of central nervous system (CNS) therapeutic compounds. The BP and SUV identified via nonradiolabeled LC-MS/MS, while different from the published values observed in the literature PET tracer data, allowed for an identification of initial criteria values we sought to facilitate increased potential for success from our early discovery screening paradigm. Our analysis showed that successful, as well as novel, clinical PET tracers exhibited BP of greater than 1.5 and peak SUVs greater than approximately 150% at 5 min post dose in rodents. The brain kinetics appeared similar between both techniques despite differences in tracer dose, suggesting linearity across these dose ranges. The assessment of tracers in a CNS exposure model, the mouse brain uptake assessment (MBUA), showed that those compound with initial brain-to-plasma ratios >2 and unbound fraction in brain homogenate >0.01 were more likely to be clinically successful PET ligands. Taken together, early incorporation of a LC/MS/MS cold tracer discovery assay and a parallel MBUA can be an useful screening paradigm to prioritize and rank order potential novel PET radioligands during early tracer discovery efforts. Compounds considered for continued in vivo PET assessments can be identified quickly by leveraging in vitro affinity and selectivity measures, coupled with data from a MBUA, primarily the 5 min brain-to-plasma ratio and unbound fraction data. Coupled utilization of these data creates a strategy to efficiently screen for the identification of appropriate chemical space to invest in for radiotracer discovery.
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Brain Activity Unique to Orgasm in Women: An fMRI Analysis.
Wise, Nan J; Frangos, Eleni; Komisaruk, Barry R
2017-11-01
Although the literature on imaging of regional brain activity during sexual arousal in women and men is extensive and largely consistent, that on orgasm is relatively limited and variable, owing in part to the methodologic challenges posed by variability in latency to orgasm in participants and head movement. To compare brain activity at orgasm (self- and partner-induced) with that at the onset of genital stimulation, immediately before the onset of orgasm, and immediately after the cessation of orgasm and to upgrade the methodology for obtaining and analyzing functional magnetic resonance imaging (fMRI) findings. Using fMRI, we sampled equivalent time points across female participants' variable durations of stimulation and orgasm in response to self- and partner-induced clitoral stimulation. The first 20-second epoch of orgasm was contrasted with the 20-second epochs at the beginning of stimulation and immediately before and after orgasm. Separate analyses were conducted for whole-brain and brainstem regions of interest. For a finer-grained analysis of the peri-orgasm phase, we conducted a time-course analysis on regions of interest. Head movement was minimized to a mean less than 1.3 mm using a custom-fitted thermoplastic whole-head and neck brace stabilizer. Ten women experienced orgasm elicited by self- and partner-induced genital stimulation in a Siemens 3-T Trio fMRI scanner. Brain activity gradually increased leading up to orgasm, peaked at orgasm, and then decreased. We found no evidence of deactivation of brain regions leading up to or during orgasm. The activated brain regions included sensory, motor, reward, frontal cortical, and brainstem regions (eg, nucleus accumbens, insula, anterior cingulate cortex, orbitofrontal cortex, operculum, right angular gyrus, paracentral lobule, cerebellum, hippocampus, amygdala, hypothalamus, ventral tegmental area, and dorsal raphe). Insight gained from the present findings could provide guidance toward a rational basis for treatment of orgasmic disorders, including anorgasmia. This is evidently the first fMRI study of orgasm elicited by self- and partner-induced genital stimulation in women. Methodologic solutions to the technical issues posed by excessive head movement and variable latencies to orgasm were successfully applied in the present study, enabling identification of brain regions involved in orgasm. Limitations include the small sample (N = 10), which combined self- and partner-induced stimulation datasets for analysis and which qualify the generalization of our conclusions. Extensive cortical, subcortical, and brainstem regions reach peak levels of activity at orgasm. Wise NJ, Frangos E, Komisaruk BR. Brain Activity Unique to Orgasm in Women: An fMRI Analysis. J Sex Med 2017;14:1380-1391. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
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Naseer, Noman; Hong, Keum-Shik
2013-10-11
This paper presents a study on functional near-infrared spectroscopy (fNIRS) indicating that the hemodynamic responses of the right- and left-wrist motor imageries have distinct patterns that can be classified using a linear classifier for the purpose of developing a brain-computer interface (BCI). Ten healthy participants were instructed to imagine kinesthetically the right- or left-wrist flexion indicated on a computer screen. Signals from the right and left primary motor cortices were acquired simultaneously using a multi-channel continuous-wave fNIRS system. Using two distinct features (the mean and the slope of change in the oxygenated hemoglobin concentration), the linear discriminant analysis classifier was used to classify the right- and left-wrist motor imageries resulting in average classification accuracies of 73.35% and 83.0%, respectively, during the 10s task period. Moreover, when the analysis time was confined to the 2-7s span within the overall 10s task period, the average classification accuracies were improved to 77.56% and 87.28%, respectively. These results demonstrate the feasibility of an fNIRS-based BCI and the enhanced performance of the classifier by removing the initial 2s span and/or the time span after the peak value. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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Gee, Dylan G; Fetcho, Robert N; Jing, Deqiang; Li, Anfei; Glatt, Charles E; Drysdale, Andrew T; Cohen, Alexandra O; Dellarco, Danielle V; Yang, Rui R; Dale, Anders M; Jernigan, Terry L; Lee, Francis S; Casey, B J
2016-04-19
Anxiety disorders peak in incidence during adolescence, a developmental window that is marked by dynamic changes in gene expression, endocannabinoid signaling, and frontolimbic circuitry. We tested whether genetic alterations in endocannabinoid signaling related to a common polymorphism in fatty acid amide hydrolase (FAAH), which alters endocannabinoid anandamide (AEA) levels, would impact the development of frontolimbic circuitry implicated in anxiety disorders. In a pediatric imaging sample of over 1,000 3- to 21-y-olds, we show effects of the FAAH genotype specific to frontolimbic connectivity that emerge by ∼12 y of age and are paralleled by changes in anxiety-related behavior. Using a knock-in mouse model of the FAAH polymorphism that controls for genetic and environmental backgrounds, we confirm phenotypic differences in frontoamygdala circuitry and anxiety-related behavior by postnatal day 45 (P45), when AEA levels begin to decrease, and also, at P75 but not before. These results, which converge across species and level of analysis, highlight the importance of underlying developmental neurobiology in the emergence of genetic effects on brain circuitry and function. Moreover, the results have important implications for the identification of risk for disease and precise targeting of treatments to the biological state of the developing brain as a function of developmental changes in gene expression and neural circuit maturation.
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Wang, Yang; Fan, Rong; Luo, Jiekun; Tang, Tao; Xing, Zhihua; Xia, Zian; Peng, Weijun; Wang, Wenzhu; Lv, Huiying; Huang, Wei; Liang, Yizeng; Yi, Lunzhao; Lu, Hongmei; Huang, Xi
2015-04-01
Damage of blood-brain barrier is a common result of traumatic brain injury. This damage can open the blood-brain barrier and allow drug passage. An ultraperformance liquid chromatography with tandem mass spectrometry method was established to determine the concentration of rhein in the biofluids (plasma and cerebrospinal fluid) of patients with a compromised blood-brain barrier following traumatic brain injury after rhubarb administration. Furthermore, the pharmacokinetic profiles were analyzed. A triple-quadruple tandem mass spectrometer with electrospray ionization was used for rhein detection. The mass transition followed was m/z 283.06→239.0. The calibration curve was linear in the concentration range of 10-8000 ng/mL for the biofluids. The intra- and interday precisions were less than 10%. The relative standard deviation of recovery was less than 15% in biological matrices. The pharmacokinetic data showed that rhein was rapidly transported into biofluids, and exhibited a peak concentration 1 h after rhubarb administration. The elimination rate of rhein was slow. The AUCcerebrospinal fluid /AUCplasma (AUC is area under curve) of rhein was approximately 17%, indicating that portions of rhein could pass the impaired blood-brain barrier. The method was successfully applied to quantify rhein in the biofluids of all patients. The data presented can help to guide clinical applications of rhubarb for treating traumatic brain injury. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Honda, Shin-Ichiro; Wakatsuki, Toru; Harada, Nobuhiro
2011-01-01
Aromatase in the mouse brain is expressed only in the nerve cells of specific brain regions with a transient peak during the neonatal period when sexual behaviors become organized. The aromatase-knockout (ArKO) mouse, generated to shed light on the physiological functions of estrogen in the brain, exhibited various abnormal behaviors, concomitant with undetectable estrogen and increased androgen in the blood. To further elucidate the effects of neurosteroidal estrogens on behavioral phenotypes, we first prepared an brain-specific aromatase transgenic (bsArTG) mouse by introduction of a human aromatase transgene controlled under a −6.5 kb upstream region of the brain-specific promoter of the mouse aromatase gene into fertilized mouse eggs, because the −6.5 kb promoter region was previously shown to contain the minimal essential element responsible for brain-specific spatiotemporal expression. Then, an ArKO mouse expressing the human aromatase only in the brain was generated by crossing the bsArTG mouse with the ArKO mouse. The resulting mice (ArKO/bsArTG mice) nearly recovered from abnormal sexual, aggressive, and locomotive (exploratory) behaviors, in spite of having almost the same serum levels of estrogen and androgen as the adult ArKO mouse. These results suggest that estrogens locally synthesized in the specific neurons of the perinatal mouse brain directly act on the neurons and play crucial roles in the organization of neuronal networks participating in the control of sexual, aggressive, and locomotive (exploratory) behaviors. PMID:22654807
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Wetzel, Hanna N; Zhang, Tongli; Norman, Andrew B
2017-09-01
A recombinant humanized anti-cocaine monoclonal antibody (mAb), h2E2, is at an advanced stage of pre-clinical development as an immunotherapy for cocaine abuse. It is hypothesized that h2E2 binds to and sequesters cocaine in the blood. A three-compartment model of the effects of h2E2 on cocaine's distribution was constructed. The model assumes that h2E2 binds to cocaine and that the h2E2-cocaine complex does not enter the brain but distributes between the central and peripheral compartments. Free cocaine is eliminated from both the central and peripheral compartments, and h2E2 and the h2E2-cocaine complex are eliminated from the central compartment only. This model was tested against a new dataset measuring cocaine concentrations in the brain and plasma over 1h in the presence and absence of h2E2. The mAb significantly increased plasma cocaine concentrations with a concomitant significant decrease in brain concentration. Plasma concentrations declined over the 1-hour sampling period in both groups. With a set of parameters within reasonable physiological ranges, the three-compartment model was able to qualitatively and quantitatively simulate the increased plasma concentration in the presence of the antibody and the decreased peak brain concentration in the presence of antibody. Importantly, the model explained the decline in plasma concentrations over time as distribution of the cocaine-h2E2 complex into a peripheral compartment. This model will facilitate the targeting of ideal mAb PK/PD properties thus accelerating the identification of lead candidate anti-drug mAbs. Copyright © 2017 Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Haj-Hosseini, Neda; Richter, Johan; Milos, Peter; Hallbeck, Martin; Wârdell, Karin
2017-02-01
In the routine of stereotactic biopsy on suspected tumors located deep in the brain or patients with multiple lesions, tissue samples are harvested to determine the type of malignancy. Biopsies are taken from pre-calculated positions based on the preoperative radiologic images susceptible to brain shift. In such cases the biopsy procedure may need to be repeated leading to a longer operation time. To provide guidance for targeting diagnostic tumor tissue and to avoid vessel rupture on the insertion path of the tumor, an application specific fiber optic probe was developed. The setup incorporated spectroscopy for 5-aminolevulinic acid induced protopophyrin IX (PpIX) fluorescence in the tumor and laser Doppler for measuring microvascular blood flow which recorded backscattered light (TLI) at 780 nm and blood perfusion. The recorded signals were compared to the histopathologic diagnosis of the tissue samples (n=16) and to the preoperative radiologic images. All together 146 fluorescence and 276 laser Doppler signals were recorded along 5 trajectories in 4 patients. On all occasions strong PpIX fluorescence peaks were visible during real-time guidance. Comparing the gliotic tumor marginal zone with the tumor, the PpIX (51 vs. 528 a.u., [0-1790], p < 0.05) was higher and TLI (2.9 vs. 2.0 a.u., [0-4.1], p < 0.05) was lower in tumor. The autofluorescence (104 vs.70 a.u., [0-442], p > 0.05) and blood perfusion (8.3 vs. 17 a.u., [0-254], p > 0.05) were not significantly different. In conclusion, the optical guidance probe made real-time tumor detection and vessel tracking possible during the stereotactic biopsy procedures. Moreover, the fluorescence and blood perfusion in the tumor could be studied at controlled positions in the brain and the tumor.
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Normal lactate concentration range in the neonatal brain.
Tomiyasu, Moyoko; Aida, Noriko; Shibasaki, Jun; Tachibana, Yasuhiko; Endo, Mamiko; Nozawa, Kumiko; Shimizu, Eiji; Tsuji, Hiroshi; Obata, Takayuki
2016-11-01
Lactate peaks are occasionally observed during in vivo magnetic resonance spectroscopy (MRS) scans of the neonatal brain, even in healthy patients. The purpose of this study was to investigate the normal range of neonatal brain lactate concentration, as a definitive normal range would be clinically valuable. Using a clinical 3T scanner (echo/repetition times, 30/5000ms), single-voxel MRS data were obtained from the basal ganglia (BG) and centrum semiovale (CS) in 48 healthy neonates (postconceptional age (PCA), 30-43weeks), nine infants (age, 1-12months old), and 20 children (age, 4-15years). Lactate concentrations were calculated using an MRS signal quantification program, LCModel. Correlations between regional lactate concentration and PCA (neonates), or age (all subjects) were investigated. Absolute lactate concentrations of the BG and CS were as follows: neonates, 0.77mM (0-2.02) [median (range)] and 0.77 (0-1.42), respectively; infants, 0.38 (0-0.79) and 0.49 (0.17-1.17); and children, 0.17 (0-0.76) and 0.22 (0-0.80). Overall, subjects' lactate concentrations decreased significantly with age (Spearman: BG, n=61, ρ=-0.38, p=0.003; CS, n=68, ρ=-0.57, p<0.001). However, during the neonatal period no correlations were detected between lactate concentration in either region and PCA. We determined normal ranges of neonatal lactate concentration, which may prove useful for diagnostic purposes. Further studies regarding changes in brain lactate concentration during development would help clarify the reasons for higher concentrations observed during the neonatal period, and contribute to improvements in diagnoses. Copyright © 2016 Elsevier Inc. All rights reserved.
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Trakoolwilaiwan, Thanawin; Behboodi, Bahareh; Lee, Jaeseok; Kim, Kyungsoo; Choi, Ji-Woong
2018-01-01
The aim of this work is to develop an effective brain-computer interface (BCI) method based on functional near-infrared spectroscopy (fNIRS). In order to improve the performance of the BCI system in terms of accuracy, the ability to discriminate features from input signals and proper classification are desired. Previous studies have mainly extracted features from the signal manually, but proper features need to be selected carefully. To avoid performance degradation caused by manual feature selection, we applied convolutional neural networks (CNNs) as the automatic feature extractor and classifier for fNIRS-based BCI. In this study, the hemodynamic responses evoked by performing rest, right-, and left-hand motor execution tasks were measured on eight healthy subjects to compare performances. Our CNN-based method provided improvements in classification accuracy over conventional methods employing the most commonly used features of mean, peak, slope, variance, kurtosis, and skewness, classified by support vector machine (SVM) and artificial neural network (ANN). Specifically, up to 6.49% and 3.33% improvement in classification accuracy was achieved by CNN compared with SVM and ANN, respectively.
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Goertz, David E.; Hynynen, Kullervo
2015-01-01
Focused ultrasound with microbubbles is an emerging technique for blood brain barrier (BBB) opening. Here, a comprehensive theoretical model of a bubble-fluid-vessel system has been developed which accounts for the bubble’s non-spherical oscillations inside a microvessel, and its resulting acoustic emissions. Numerical simulations of unbound and confined encapsulated bubbles were performed to evaluate the effect of the vessel wall on acoustic emissions and vessel wall stresses. Using a Marmottant shell model, the normalized second harmonic to fundamental emissions first decreased as a function of pressure (>50 kPa) until reaching a minima ("transition point") at which point they increased. The transition point of unbound compared to confined bubble populations occurred at different pressures and was associated with an accompanying increase in shear and circumferential wall stresses. As the wall stresses depend on the bubble to vessel wall distance, the stresses were evaluated for bubbles with their wall at a constant distance to a flat wall. As a result, the wall stresses were bubble size and frequency dependent and the peak stress values induced by bubbles larger than resonance remained constant versus frequency at a constant mechanical index. PMID:25546853
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Levy, R.P.; Fabrikant, J.I.; Phillips, M.H.
1989-12-01
Angiographically occult vascular malformations (AOVMs) of the brain have been recognized for many years to cause neurologic morbidity and mortality. They generally become symptomatic due to intracranial hemorrhage, focal mass effect, seizures or headaches. The true incidence of AOVMs is unknown, but autopsy studies suggest that they are more common than high-flow angiographically demonstrable arteriovenous malformations (AVMs). We have developed stereotactic heavy-charged-particle Bragg peak radiosurgery for the treatment of inoperable intracranial vascular malformations, using the helium ion beams at the Lawrence Berkeley Laboratory 184-inch Synchrocyclotron and Bevatron. This report describes the protocol for patient selection, radiosurgical treatment planning method, clinicalmore » and neuroradiologic results and complications encountered, and discusses the strengths and limitations of the method. 10 refs., 1 fig.« less
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Effect of respiratory and cardiac gating on the major diffusion-imaging metrics
Hamaguchi, Hiroyuki; Sugimori, Hiroyuki; Nakanishi, Mitsuhiro; Nakagawa, Shin; Fujiwara, Taro; Yoshida, Hirokazu; Takamori, Sayaka; Shirato, Hiroki
2016-01-01
The effect of respiratory gating on the major diffusion-imaging metrics and that of cardiac gating on mean kurtosis (MK) are not known. For evaluation of whether the major diffusion-imaging metrics—MK, fractional anisotropy (FA), and mean diffusivity (MD) of the brain—varied between gated and non-gated acquisitions, respiratory-gated, cardiac-gated, and non-gated diffusion-imaging of the brain were performed in 10 healthy volunteers. MK, FA, and MD maps were constructed for all acquisitions, and the histograms were constructed. The normalized peak height and location of the histograms were compared among the acquisitions by use of Friedman and post hoc Wilcoxon tests. The effect of the repetition time (TR) on the diffusion-imaging metrics was also tested, and we corrected for its variation among acquisitions, if necessary. The results showed a shift in the peak location of the MK and MD histograms to the right with an increase in TR (p ≤ 0.01). The corrected peak location of the MK histograms, the normalized peak height of the FA histograms, the normalized peak height and the corrected peak location of the MD histograms varied significantly between the gated and non-gated acquisitions (p < 0.05). These results imply an influence of respiration and cardiac pulsation on the major diffusion-imaging metrics. The gating conditions must be kept identical if reproducible results are to be achieved. PMID:27073115
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Haffmans, J; De Kloet, R; Dzoljic, M R
1984-06-04
The glucose utilization during specific delta opiate agonist-induced epileptiform phenomena, determined by the [14C]2-deoxyglucose technique (2-DG), was examined in various rat brain areas at different time intervals. The peak in EEG spiking response and the most intensive 2-DG uptake occurred 5 min after intraventricular (i.v.t.) administration of the delta opiate receptor agonist. The most pronounced 2-DG uptake at this time interval can be observed in the subiculum, including the CA1 hippocampal area, frontal cortex and central amygdala. A general decrease of glucose consumption, compared to control values, is observed after 10 min, in all regions, with exception of the subiculum. Since functional activity and 2-DG uptake are correlated, we suggest that the subiculum and/or CA1 area, are probably the brain regions most involved in the enkephalin-induced epileptic phenomena.
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Computer assisted diagnostic system in tumor radiography.
Faisal, Ahmed; Parveen, Sharmin; Badsha, Shahriar; Sarwar, Hasan; Reza, Ahmed Wasif
2013-06-01
An improved and efficient method is presented in this paper to achieve a better trade-off between noise removal and edge preservation, thereby detecting the tumor region of MRI brain images automatically. Compass operator has been used in the fourth order Partial Differential Equation (PDE) based denoising technique to preserve the anatomically significant information at the edges. A new morphological technique is also introduced for stripping skull region from the brain images, which consequently leading to the process of detecting tumor accurately. Finally, automatic seeded region growing segmentation based on an improved single seed point selection algorithm is applied to detect the tumor. The method is tested on publicly available MRI brain images and it gives an average PSNR (Peak Signal to Noise Ratio) of 36.49. The obtained results also show detection accuracy of 99.46%, which is a significant improvement than that of the existing results.
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The heart-break of social rejection versus the brain wave of social acceptance
van der Molen, Maurits W.; Sahibdin, Priya P.; Franken, Ingmar H. A.
2014-01-01
The effect of social rejection on cardiac and brain responses was examined in a study in which participants had to decide on the basis of pictures of virtual peers whether these peers would like them or not. Physiological and behavioral responses to expected and unexpected acceptance and rejection were compared. It was found that participants expected that about 50% of the virtual judges gave them a positive judgment. Cardiac deceleration was strongest for unexpected social rejection. In contrast, the brain response was strongest to expected acceptance and was characterized by a positive deflection peaking around 325 ms following stimulus onset and the observed difference was maximal at fronto-central positions. The cardiac and electro-cortical responses were not related. It is hypothesized that these differential response patterns might be related to earlier described differential involvement of the dorsal and ventral portion of the anterior cingulate cortex. PMID:23887821
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Teoh, Jia-Jie; Iwano, Tomohiko; Kunii, Masataka; Atik, Nur; Avriyanti, Erda; Yoshimura, Shin-ichiro; Moriwaki, Kenta
2017-01-01
BIG1, an activator protein of the small GTPase, Arf, and encoded by the Arfgef1 gene, is one of candidate genes for epileptic encephalopathy. To know the involvement of BIG1 in epileptic encephalopathy, we analyzed BIG1-deficient mice and found that BIG1 regulates neurite outgrowth and brain development in vitro and in vivo. The loss of BIG1 decreased the size of the neocortex and hippocampus. In BIG1-deficient mice, the neuronal progenitor cells (NPCs) and the interneurons were unaffected. However, Tbr1+ and Ctip2+ deep layer (DL) neurons showed spatial-temporal dependent apoptosis. This apoptosis gradually progressed from the piriform cortex (PIR), peaked in the neocortex, and then progressed into the hippocampus from embryonic day 13.5 (E13.5) to E17.5. The upper layer (UL) and DL order in the neocortex was maintained in BIG1-deficient mice, but the excitatory neurons tended to accumulate before their destination layers. Further pulse-chase migration assay showed that the migration defect was non-cell autonomous and secondary to the progression of apoptosis into the BIG1-deficient neocortex after E15.5. In BIG1-deficient mice, we observed an ectopic projection of corticothalamic axons from the primary somatosensory cortex (S1) into the dorsal lateral geniculate nucleus (dLGN). The thalamocortical axons were unable to cross the diencephalon–telencephalon boundary (DTB). In vitro, BIG1-deficient neurons showed a delay in neuronal polarization. BIG1-deficient neurons were also hypersensitive to low dose glutamate (5 μM), and died via apoptosis. This study showed the role of BIG1 in the survival of DL neurons in developing embryonic brain and in the generation of neuronal polarity. PMID:28414797
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Andersson, Jan D; Varnäs, Katarina; Cselényi, Zsolt; Gulyás, Balázs; Wensbo, David; Finnema, Sjoerd J; Swahn, Britt-Marie; Svensson, Samuel; Nyberg, Svante; Farde, Lars; Halldin, Christer
2010-10-01
Beta-amyloid accumulation is associated with the pathogenesis of Alzheimer's disease (AD). AZD2184, a new radioligand for high-contrast positron emission tomography (PET) imaging of Abeta-deposits, has recently been developed and characterized in vitro and in rodents ex vivo. The objective of this study was to label AZD2184 with carbon-11, to perform in vivo characterization of [(11)C]AZD2184 ([(11)C]5) in the cynomolgus monkey brain as well as whole-body dosimetry, and to examine the metabolism of the labeled radioligand. [(11)C]5 was prepared by a two-step radiosynthesis starting with the reaction of 5-(6-(tert-butyldimethylsilyloxy)benzo[d]thiazol-2-yl)pyridin-2-amine with [(11)C]methyl iodide followed by deprotection using water. Four brain PET measurements in two cynomolgus monkeys and one whole-body PET measurement were performed with [(11)C]5. There was a high and rapid brain uptake (2.2-3.4% of injected dose at 2 min). The distribution of brain radioactivity was fairly uniform, with early to late-brain concentration ratios (peak vs. 60 min) higher for [(11)C]5 than ratios previously reported for [(11)C]PIB (8.2 and 4.6, respectively). Based on the whole-body data, it was estimated that an effective dose in an adult male would be 6.2 muSv/MBq and thus would be safe from a radiation point of view for multiple scans within the same year. [(11)C]5 shows binding characteristics, suggesting low levels of white-matter retention, and may thus provide improved contrast when compared with currently used PET radioligands for visualization of Abeta-deposits. On the basis of the labeling chemistry and the results of the biological evaluation, we conclude that [(11)C]5 should be useful for routine clinical studies. (c) 2010 Wiley-Liss, Inc.
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Gautier, Yentl; Luneau, Isabelle; Coquery, Nicolas; Meurice, Paul; Malbert, Charles-Henri; Guerin, Sylvie; Kemp, Bas; Bolhuis, J Elizabeth; Clouard, Caroline; Le Huërou-Luron, Isabelle; Blat, Sophie; Val-Laillet, David
2018-06-13
This study explores the long-term effects of exposure to a maternal Western diet (WD) vs. standard diet (SD) in the Yucatan minipig, on the adult progeny at lean status ( n = 32), and then overweight status. We investigated eating behavior, cognitive abilities, brain basal glucose metabolism, dopamine transporter availability, microbiota activity, blood lipids, and glucose tolerance. Although both groups demonstrated similar cognitive abilities in a holeboard test, WD pigs expressed a higher stress level than did SD pigs (immobility, P < 0.05) and lower performance in an alley maze ( P = 0.06). WD pigs demonstrated lower dopamine transporter binding potential in the hippocampus and parahippocampal cortex ( P < 0.05 for both), as well as a trend in putamen ( P = 0.07), associated with lower basal brain activity in the prefrontal cortex and nucleus accumbens ( P < 0.05) compared with lean SD pigs. Lean WD pigs demonstrated a lower glucose tolerance than did SD animals (higher glucose peak, P < 0.05) and a tendency to a higher incremental area under the curve of insulin from 0 to 30 minutes after intravenous glucose injection ( P < 0.1). Both groups developed glucose intolerance with overweight, but WD animals were less impacted than SD animals. These results demonstrate that maternal diet shaped the offspring's brain functions and cognitive responses long term, even after being fed a balanced diet from weaning, but behavioral effects were only revealed in WD pigs under anxiogenic situation; however, WD animals seemed to cope better with the obesogenic diet from a metabolic standpoint.-Gautier, Y., Luneau, I., Coquery, N., Meurice, P., Malbert, C.-H., Guerin, S., Kemp, B., Bolhuis, J. E., Clouard, C., Le Huërou-Luron, I., Blat, S., Val-Laillet, D. Maternal Western diet during gestation and lactation modifies adult offspring's cognitive and hedonic brain processes, behavior, and metabolism in Yucatan minipigs.
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Bushi, Doron; Stein, Efrat Shavit; Golderman, Valery; Feingold, Ekaterina; Gera, Orna; Chapman, Joab; Tanne, David
2017-01-01
Brain thrombin activity is increased following acute ischemic stroke and may play a pathogenic role through the protease-activated receptor 1 (PAR1). In order to better assess these factors, we obtained a novel detailed temporal and spatial profile of thrombin activity in a mouse model of permanent middle cerebral artery occlusion (pMCAo). Thrombin activity was measured by fluorescence spectroscopy on coronal slices taken from the ipsilateral and contralateral hemispheres 2, 5, and 24 h following pMCAo ( n = 5, 6, 5 mice, respectively). Its spatial distribution was determined by punch samples taken from the ischemic core and penumbra and further confirmed using an enzyme histochemistry technique ( n = 4). Levels of PAR1 were determined using western blot. Two hours following pMCAo, thrombin activity in the stroke core was already significantly higher than the contralateral area (11 ± 5 vs. 2 ± 1 mU/ml). At 5 and 24 h, thrombin activity continued to rise linearly ( r = 0.998, p = 0.001) and to expand in the ischemic hemisphere beyond the ischemic core reaching deleterious levels of 271 ± 117 and 123 ± 14 mU/ml (mean ± SEM) in the basal ganglia and ischemic cortex, respectively. The peak elevation of thrombin activity in the ischemic core that was confirmed by fluorescence histochemistry was in good correlation with the infarcts areas. PAR1 levels in the ischemic core decreased as stroke progressed and thrombin activity increased. In conclusion, there is a time- and space-related increase in brain thrombin activity in acute ischemic stroke that is closely related to the progression of brain damage. These results may be useful in the development of therapeutic strategies for ischemic stroke that involve the thrombin-PAR1 pathway in order to prevent secondary thrombin related brain damage.
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Photoacoustic micro-imaging of focused ultrasound induced blood-brain-barrier opening in a rat model
NASA Astrophysics Data System (ADS)
Wang, Po-Hsun; Hsu, Po-Hung; Liu, Hao-Li; Wang, Churng-Ren Chris; Li, Meng-Lin
2010-02-01
Blood brain barrier (BBB) prevents most of the drug from transmitting into the brain tissue and decreases the treatment performance for brain disease. One of the methods to overcome the difficulty of drug delivery is to locally increase the permeability of BBB with high-intensity focused ultrasound. In this study, we have investigated the feasibility of photoacoustic microscopy of focused-ultrasound induced BBB opening in a rat model in vivo with gold nanorods (AuNRs) as a contrast agent. This study takes advantage of the strong near-infrared absorption of AuNRs and their extravasation tendency from BBB opening foci due to their nano-scale size. Before the experiments, craniotomy was performed on rats to provide a path for focused ultrasound beam. Localized BBB opening at the depth of about 3 mm from left cortex of rat brains was achieved by delivering 1.5 MHz focused ultrasound energy into brain tissue in the presence of microbubbles. PEGylated AuNRs with a peak optical absorption at ~800 nm were then intravenously administered. Pre-scan prior to BBB disruption and AuNR injection was taken to mark the signal background. After injection, the distribution of AuNRs in rat brains was monitored up to 2 hours. Experimental results show that imaging AuNRs reveals BBB disruption area in left brains while there are no changes observed in the right brains. From our results, photoacoustic imaging plus AuNRs shows the promise as a novel monitoring strategy in identifying the location and variation of focused-ultrasound BBB-opening in a rat model.
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Spectral Variability in the Aged Brain during Fine Motor Control
Quandt, Fanny; Bönstrup, Marlene; Schulz, Robert; Timmermann, Jan E.; Zimerman, Maximo; Nolte, Guido; Hummel, Friedhelm C.
2016-01-01
Physiological aging is paralleled by a decline of fine motor skills accompanied by structural and functional alterations of the underlying brain network. Here, we aim to investigate age-related changes in the spectral distribution of neuronal oscillations during fine skilled motor function. We employ the concept of spectral entropy in order to describe the flatness and peaked-ness of a frequency spectrum to quantify changes in the spectral distribution of the oscillatory motor response in the aged brain. Electroencephalogram was recorded in elderly (n = 32) and young (n = 34) participants who performed either a cued finger movement or a pinch or a whole hand grip task with their dominant right hand. Whereas young participant showed distinct, well-defined movement-related power decreases in the alpha and upper beta band, elderly participants exhibited a flat broadband, frequency-unspecific power desynchronization. This broadband response was reflected by an increase of spectral entropy over sensorimotor and frontal areas in the aged brain. Neuronal activation patterns differed between motor tasks in the young brain, while the aged brain showed a similar activation pattern in all tasks. Moreover, we found a wider recruitment of the cortical motor network in the aged brain. The present study adds to the understanding of age-related changes of neural coding during skilled motor behavior, revealing a less predictable signal with great variability across frequencies in a wide cortical motor network in the aged brain. The increase in entropy in the aged brain could be a reflection of random noise-like activity or could represent a compensatory mechanism that serves a functional role. PMID:28066231
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Brain Development and Its Relationship to Early Childhood Education.
ERIC Educational Resources Information Center
Slegers, Brenda
New research on brain development has profound implications in the areas of child development and education. This review of the research describes how the brain develops to shape children's growing intelligence, addressing such questions as: (1) What are the brain's functions? (2) What are the critical or sensitive periods in brain development?…
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Liang, Yu-Zhi; Zeng, Zhi-Lei; Hua, Lin-Lin; Li, Jin-Feng; Wang, Yun-Liang; Bi, Xi-Zhuang
2016-06-01
To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with ischemia reperfusion. A total of 60 male Wistar rats were randomly divided into the normal group, sham group, diabetic cerebral infarction group and single cerebral infarction group according to the random number table, with 15 rats in each group. The high sucrose diet and intraperitoneal injection of streptozotocin were performed for the modeling of diabetic rats, while the thread-occlusion method was employed to build the model of cerebral ischemia reperfusion. The immunohistochemical staining was performed to detect the expression of angiostatin, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in the brain tissue. The expression of angiostatin after the reperfusion in the brain tissue of rats in the single cerebral infarction group and diabetic cerebral infarction group was increased 6 h after the reperfusion, reached to the peak on 1 d and then decreased gradually. The expression of angiostatin in the diabetic cerebral infarction group 6 h, 1 d, 3 d and 7 d after the reperfusion was significantly higher than that in the single cerebral infarction group (P < 0.05). VEGF began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak at 6 h and then decreased gradually. The expression of VEGF in the diabetic cerebral infarction group at each time point after the reperfusion was significantly lower than that in the single cerebral infarction group (P < 0.05). MMP-9 began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak on 1 d and then decreased gradually. The expression of MMP-9 in the diabetic cerebral infarction group at each time point after the reperfusion was significantly higher than that in the single cerebral infarction group (P < 0.05). The high glucose environment in which the diabetic cerebral infarction is occurred is to induce the formation of MMP-9 at first and then activate and increase the expression of angiostatin. Afterwards, the expression of VEGF is inhibited, resulting in the poor angiogenesis after cerebral infarction, which thus makes the injury of brain tissue after cerebral infarction even worse than the non-diabetes mellitus. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.
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Mohaibes, Raheem J; Fiol-deRoque, María A; Torres, Manuel; Ordinas, Margarita; López, David J; Castro, José A; Escribá, Pablo V; Busquets, Xavier
2017-09-01
We have compared the effect of the commonly used ω-3 fatty acid, docosahexaenoic acid ethyl ester (DHA-EE), and of its 2-hydroxylated DHA form (DHA-H), on brain lipid composition, behavior and lifespan in a new human transgenic Drosophila melanogaster model of Alzheimer's disease (AD). The transgenic flies expressed human Aβ42 and tau, and the overexpression of these human transgenes in the CNS of these flies produced progressive defects in motor function (antigeotaxic behavior) while reducing the animal's lifespan. Here, we demonstrate that both DHA-EE and DHA-H increase the longer chain fatty acids (≥18C) species in the heads of the flies, although only DHA-H produced an unknown chromatographic peak that corresponded to a non-hydroxylated lipid. In addition, only treatment with DHA-H prevented the abnormal climbing behavior and enhanced the lifespan of these transgenic flies. These benefits of DHA-H were confirmed in the well characterized transgenic PS1/APP mouse model of familial AD (5xFAD mice), mice that develop defects in spatial learning and in memory, as well as behavioral deficits. Hence, it appears that the modulation of brain lipid composition by DHA-H could have remedial effects on AD associated neurodegeneration. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017. Published by Elsevier B.V.
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Nature, life and mind. An essay on the essence.
Marinkovic, S; Pajić, S; Tomić, O
Our long-standing scientific work and love to the fine art and nature for many years succeeded in making a unifying description of the three domains, at a time when a high specialisation in science, and even in art, has neglected the necessary entirety. Some neurons of a rat cerebral cortex were labelled with true blue and photographed under a fluorescent microscope. A monkey brain was sectioned in the axial plane. Several slices of the human motor cortex were stained with cresyl violet. A cerebral hemisphere image was modified, and another image was created in Adobe Photoshop. Some 10 billion years after the Big Bang life appeared on the Earth, reaching its peak with development of the brain. The humans started exploration of the local nature to survive, and the universe for psychological support. The antique philosophers Leucippes, Democritus and Heraclitus were the first to create a unifying atomic theory and to suggest the eternal movement of the matter. Newton and Kepler explained the movement of the celestial objects, whereas Einstein, Planck, Bohr, Hubbel, Howking and many others connected the quantum physics and elementary forces with the essence of the universe. Leonardo da Vinci, and later many others as well, united science and art. Philosophers and mathematicians created the phenomena which do not exist in nature. Nature designed the human brain, more complex than the universe itself, which in turn created millions of the artworks and scientific discoveries. The might of the mind in some domains overcomes the power of nature.
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Music for the Very Young: How to Use the Suzuki Method in the Preschool Classroom
ERIC Educational Resources Information Center
Garner, Alison Maerker
2008-01-01
Music learning and music performance involve all aspects of the individual: cognitive, emotional, social, and psychomotor. John Feierabend shows that music requires a special kind of intellectual process that is unique to the discipline. Brain density reaches its peak in a child's first few years of life; hence, as with language, music learning…
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Modulation of neurotoxic behavior in F-344 rats by temporal disposition of benzo(a)pyrene.
Saunders, Crystal R; Ramesh, Aramandla; Shockley, Dolores C
2002-03-24
The behavioral changes caused by benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound, were monitored, and also its metabolite levels in cerebellum and cortex were measured in BaP treated rats to see if any relationship existed between these two aspects. Rats were administered 0, 25, 50, 100, and 200 mg/kg of BaP in peanut oil by oral gavage. Plasma, and brain tissue (cerebellum and cortex) samples were collected at 0, 2, 4, 6, 12, 24, 48, 72 and 96 h post administration. Neurotoxic effects peaked at 2 h after dosing and lasted 48 h after dosing for all dose groups. The metabolite levels remained the same from 2 to 4 h, reached a peak at 6 h post gavage and showed a gradual decline returning to baseline levels at 72 h when the motor activity of treatment groups also returned to control levels, indicating recovery from the effects of BaP. A significant (P<0.05) correlation between neurotoxic effects and BaP plasma, and brain metabolite concentrations suggests that metabolism plays an important role in modulating the neurobehavioral effects of BaP.
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Age-dependent tissue-specific exposure of cell phone users.
Christ, Andreas; Gosselin, Marie-Christine; Christopoulou, Maria; Kühn, Sven; Kuster, Niels
2010-04-07
The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.
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Neurofeedback training for peak performance.
Graczyk, Marek; Pąchalska, Maria; Ziółkowski, Artur; Mańko, Grzegorz; Łukaszewska, Beata; Kochanowicz, Kazimierz; Mirski, Andrzej; Kropotov, Iurii D
2014-01-01
One of the applications of the Neurofeedback methodology is peak performance in sport. The protocols of the neurofeedback are usually based on an assessment of the spectral parameters of spontaneous EEG in resting state conditions. The aim of the paper was to study whether the intensive neurofeedback training of a well-functioning Olympic athlete who has lost his performance confidence after injury in sport, could change the brain functioning reflected in changes in spontaneous EEG and event related potentials (ERPs). The case is presented of an Olympic athlete who has lost his performance confidence after injury in sport. He wanted to resume his activities by means of neurofeedback training. His QEEG/ERP parameters were assessed before and after 4 intensive sessions of neurotherapy. Dramatic and statistically significant changes that could not be explained by error measurement were observed in the patient. Neurofeedback training in the subject under study increased the amplitude of the monitoring component of ERPs generated in the anterior cingulate cortex, accompanied by an increase in beta activity over the medial prefrontal cortex. Taking these changes together, it can be concluded that that even a few sessions of neurofeedback in a high performance brain can significantly activate the prefrontal cortical areas associated with increasing confidence in sport performance.
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Age-dependent tissue-specific exposure of cell phone users
NASA Astrophysics Data System (ADS)
Christ, Andreas; Gosselin, Marie-Christine; Christopoulou, Maria; Kühn, Sven; Kuster, Niels
2010-04-01
The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.
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Three-dimensional MRI perfusion maps: a step beyond volumetric analysis in mental disorders
Fabene, Paolo F; Farace, Paolo; Brambilla, Paolo; Andreone, Nicola; Cerini, Roberto; Pelizza, Luisa; Versace, Amelia; Rambaldelli, Gianluca; Birbaumer, Niels; Tansella, Michele; Sbarbati, Andrea
2007-01-01
A new type of magnetic resonance imaging analysis, based on fusion of three-dimensional reconstructions of time-to-peak parametric maps and high-resolution T1-weighted images, is proposed in order to evaluate the perfusion of selected volumes of interest. Because in recent years a wealth of data have suggested the crucial involvement of vascular alterations in mental diseases, we tested our new method on a restricted sample of schizophrenic patients and matched healthy controls. The perfusion of the whole brain was compared with that of the caudate nucleus by means of intrasubject analysis. As expected, owing to the encephalic vascular pattern, a significantly lower time-to-peak was observed in the caudate nucleus than in the whole brain in all healthy controls, indicating that the suggested method has enough sensitivity to detect subtle perfusion changes even in small volumes of interest. Interestingly, a less uniform pattern was observed in the schizophrenic patients. The latter finding needs to be replicated in an adequate number of subjects. In summary, the three-dimensional analysis method we propose has been shown to be a feasible tool for revealing subtle vascular changes both in normal subjects and in pathological conditions. PMID:17229290
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Lenz, Kathryn M; Nelson, Lars H
2018-01-01
Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer's disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life. We also summarize the effects of early life perturbations on microglia function in the developing brain, the role that biological sex plays in microglia function, and the potential role that microglia may play in developmental brain disorders. Finally, given how new the field of developmental neuroimmunology is, we highlight what has yet to be learned about how innate immune cells shape the development of brain and behavior.
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Brain development and the nature versus nurture debate.
Stiles, Joan
2011-01-01
Over the past three decades, developmental neurobiologists have made tremendous progress in defining basic principles of brain development. This work has changed the way we think about how brains develop. Thirty years ago, the dominant model was strongly deterministic. The relationship between brain and behavioral development was viewed as unidirectional; that is, brain maturation enables behavioral development. The advent of modern neurobiological methods has provided overwhelming evidence that it is the interaction of genetic factors and the experience of the individual that guides and supports brain development. Brains do not develop normally in the absence of critical genetic signaling, and they do not develop normally in the absence of essential environmental input. The fundamental facts about brain development should be of critical importance to neuropsychologists trying to understand the relationship between brain and behavioral development. However, the underlying assumptions of most contemporary psychological models reflect largely outdated ideas about how the biological system develops and what it means for something to be innate. Thus, contemporary models of brain development challenge the foundational constructs of the nature versus nurture formulation in psychology. The key to understanding the origins and emergence of both the brain and behavior lies in understanding how inherited and environmental factors are engaged in the dynamic and interactive processes that define and guide development of the neurobehavioral system. Copyright © 2011 Elsevier B.V. All rights reserved.
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2008-06-26
Homo sapiens decorin variant C mRNA, complete cds. 2.117 PKNOX2 HUM408A08B Human fetal brain (TFujiwara) Homo sapiens cDNA clone GEN -408A08 5’, mRNA...mRNA, complete cds. 2.117 PKNOX2 HUM408A08B Human fetal brain (TFujiwara) Homo sapiens cDNA clone GEN -408A08 5’, mRNA sequence. 2.076 SEC23B...RAS oncogene family ; RAB33B, member RAS oncogene family 205300_s_at 0.37 U1SNRNPBP U11/U12 snRNP 35K 220728_at 0.349 218689_at 0.342 FANCF Fanconi
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Guan, Jingxia; Zhang, Shaofeng; Zhou, Qin; Yuan, Zhenhua; Lu, Zuneng
2016-09-01
To investigate the effect of thrombin preconditioning (TPC) on the intracerebral hemorrhage (ICH)-induced proliferation, migration, and function of subventriclular zone (SVZ) cells and to find new strategies that enhance endogenous neurogenesis after ICH. Male Sprague-Dawley rats were randomly divided into 3 groups (ICH, TPC, and control group). Rats of each group were randomly divided into 5 subgroups (3-d, 7-d, 14-d, 21-d, and 28-d subgroup). ICH was caused by intrastrial stereotactic administration of collagenase type IV. Brdu was used to label newborn SVZ cells. Organotypic brain slices were cultured to dynamically observe the migration of SVZ cells at living brain tissue. Migration of Dil-labeled SVZ cells in living brain slices was traced by time-lapse microscopy. To assess whether SVZ cells migrating to injured striatum had the ability to form synapses with other cells, brain slices from each group were double immunolabeled with Brdu and synapsin I. The number of Brdu-positive cells markedly increased in the ipsilateral SVZ and striatum 3 days after TPC, peaked at 14 days (P < 0.01), continued to 21 days, and then gradually decreased at 28 days with significant difference compared to the ICH group at each time point (P < 0.01). Migration of Dil-labeled SVZ cells in brain slices in each group was observed and imaged during a 12-h period. Dil-labeled SVZ cells in the TPC group were observed to migrate laterally toward striatum with time with a faster velocity compared to the ICH group (P < 0.01). Our study also demonstrated that TPC induced strong colocalization of Brdu and synapsin I in the ipsilateral striatum between 3 and 28 days after injury.TPC made colocalization of Brdu and synapsin I appear earlier and continue for a longer time compared to the ICH group. Our results demonstrated that TPC could promote proliferation, migration, and function of SVZ cells after ICH, which may provide a new idea for enhancing endogenous neurogenesis and developing new therapeutic strategies against ICH-induced brain injury.
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Studies in nonlinear optics and functional magnetic resonance imaging
NASA Astrophysics Data System (ADS)
Dai, Tehui
There are two parts in this thesis. The first part will involve a study in the anomalous dispersion phase matched second-harmonic generation, and the second part will be a study in functional magnetic resonance imaging (fMRI) and a biophysical model of the human muscle. In part I, we report on a series of tricyanovinylaniline chromophores for use as dopants in poled poly(methyl methacrylate) waveguides for anomalous-dispersion phase- matched second-harmonic generation. Second-harmonic generation measurements as a function of mode index confirmed anomalous dispersion phase-matching efficiencies as large as 245%/Wcm2 over a propagation length of ~35 μm. The waveguide coupling technique limited the interaction length. The photostability of the chromophores was measured directly and found to agree qualitatively with second-harmonic measurements over time and was found to be improved over previously reported materials. In part II, we designed a system that could record joint force and surface electromyography (EMG) simultaneously with fMRI data. I-Egh quality force and EMG data were obtained at the same time that excellent fMRI brain images were achieved. Using this system we determined the relationship between the fMRI-measured brain activation and the handgrip force, and between the fMRI-measured brain activation and the EMG of finger flexor muscles. We found that in the whole brain and in the majority of motor function-related cortical fields, the degree of muscle activation is directly proportional to the amplitude of the brain signal determined by the fMRI measurement. The similarity in the relationship between muscle output and fMRI signal in a number of brain areas suggests that multiple cortical fields are involved in controlling muscle force. The factors that may contribute to the fMRI signals are discussed. A biophysical twitch force model was developed to predict force response under electrical stimulation. Comparison between experimental and modeled force profiles, peak forces, and force duration shows excellent agreement between the model and the experimental data. It is concluded that the present model allows us to reproduce the main features of muscle activation under stimulation.
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Mobile phone types and SAR characteristics of the human brain.
Lee, Ae-Kyoung; Hong, Seon-Eui; Kwon, Jong-Hwa; Choi, Hyung-Do; Cardis, Elisabeth
2017-04-07
Mobile phones differ in terms of their operating frequency, outer shape, and form and location of the antennae, all of which affect the spatial distributions of their electromagnetic field and the level of electromagnetic absorption in the human head or brain. For this paper, the specific absorption rate (SAR) was calculated for four anatomical head models at different ages using 11 numerical phone models of different shapes and antenna configurations. The 11 models represent phone types accounting for around 86% of the approximately 1400 commercial phone models released into the Korean market since 2002. Seven of the phone models selected have an internal dual-band antenna, and the remaining four possess an external antenna. Each model was intended to generate an average absorption level equivalent to that of the same type of commercial phone model operating at the maximum available output power. The 1 g peak spatial SAR and ipsilateral and contralateral brain-averaged SARs were reported for all 11 phone models. The effects of the phone type, phone position, operating frequency, and age of head models on the brain SAR were comprehensively determined.
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Williams, Shawniqua T; Conte, Mary M; Goldfine, Andrew M; Noirhomme, Quentin; Gosseries, Olivia; Thonnard, Marie; Beattie, Bradley; Hersh, Jennifer; Katz, Douglas I; Victor, Jonathan D; Laureys, Steven; Schiff, Nicholas D
2013-01-01
Zolpidem produces paradoxical recovery of speech, cognitive and motor functions in select subjects with severe brain injury but underlying mechanisms remain unknown. In three diverse patients with known zolpidem responses we identify a distinctive pattern of EEG dynamics that suggests a mechanistic model. In the absence of zolpidem, all subjects show a strong low frequency oscillatory peak ∼6–10 Hz in the EEG power spectrum most prominent over frontocentral regions and with high coherence (∼0.7–0.8) within and between hemispheres. Zolpidem administration sharply reduces EEG power and coherence at these low frequencies. The ∼6–10 Hz activity is proposed to arise from intrinsic membrane properties of pyramidal neurons that are passively entrained across the cortex by locally-generated spontaneous activity. Activation by zolpidem is proposed to arise from a combination of initial direct drug effects on cortical, striatal, and thalamic populations and further activation of underactive brain regions induced by restoration of cognitively-mediated behaviors. DOI: http://dx.doi.org/10.7554/eLife.01157.001 PMID:24252875
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Mobile phone types and SAR characteristics of the human brain
NASA Astrophysics Data System (ADS)
Lee, Ae-Kyoung; Hong, Seon-Eui; Kwon, Jong-Hwa; Choi, Hyung-Do; Cardis, Elisabeth
2017-04-01
Mobile phones differ in terms of their operating frequency, outer shape, and form and location of the antennae, all of which affect the spatial distributions of their electromagnetic field and the level of electromagnetic absorption in the human head or brain. For this paper, the specific absorption rate (SAR) was calculated for four anatomical head models at different ages using 11 numerical phone models of different shapes and antenna configurations. The 11 models represent phone types accounting for around 86% of the approximately 1400 commercial phone models released into the Korean market since 2002. Seven of the phone models selected have an internal dual-band antenna, and the remaining four possess an external antenna. Each model was intended to generate an average absorption level equivalent to that of the same type of commercial phone model operating at the maximum available output power. The 1 g peak spatial SAR and ipsilateral and contralateral brain-averaged SARs were reported for all 11 phone models. The effects of the phone type, phone position, operating frequency, and age of head models on the brain SAR were comprehensively determined.
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Transcranial focused ultrasound stimulation of human primary visual cortex
NASA Astrophysics Data System (ADS)
Lee, Wonhye; Kim, Hyun-Chul; Jung, Yujin; Chung, Yong An; Song, In-Uk; Lee, Jong-Hwan; Yoo, Seung-Schik
2016-09-01
Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.
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Genomic connectivity networks based on the BrainSpan atlas of the developing human brain
NASA Astrophysics Data System (ADS)
Mahfouz, Ahmed; Ziats, Mark N.; Rennert, Owen M.; Lelieveldt, Boudewijn P. F.; Reinders, Marcel J. T.
2014-03-01
The human brain comprises systems of networks that span the molecular, cellular, anatomic and functional levels. Molecular studies of the developing brain have focused on elucidating networks among gene products that may drive cellular brain development by functioning together in biological pathways. On the other hand, studies of the brain connectome attempt to determine how anatomically distinct brain regions are connected to each other, either anatomically (diffusion tensor imaging) or functionally (functional MRI and EEG), and how they change over development. A global examination of the relationship between gene expression and connectivity in the developing human brain is necessary to understand how the genetic signature of different brain regions instructs connections to other regions. Furthermore, analyzing the development of connectivity networks based on the spatio-temporal dynamics of gene expression provides a new insight into the effect of neurodevelopmental disease genes on brain networks. In this work, we construct connectivity networks between brain regions based on the similarity of their gene expression signature, termed "Genomic Connectivity Networks" (GCNs). Genomic connectivity networks were constructed using data from the BrainSpan Transcriptional Atlas of the Developing Human Brain. Our goal was to understand how the genetic signatures of anatomically distinct brain regions relate to each other across development. We assessed the neurodevelopmental changes in connectivity patterns of brain regions when networks were constructed with genes implicated in the neurodevelopmental disorder autism (autism spectrum disorder; ASD). Using graph theory metrics to characterize the GCNs, we show that ASD-GCNs are relatively less connected later in development with the cerebellum showing a very distinct expression of ASD-associated genes compared to other brain regions.
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Identification of a novel dynamic red blindness in human by event-related brain potentials.
Zhang, Jiahua; Kong, Weijia; Yang, Zhongle
2010-12-01
Dynamic color is an important carrier that takes information in some special occupations. However, up to the present, there are no available and objective tests to evaluate dynamic color processing. To investigate the characteristics of dynamic color processing, we adopted two patterns of visual stimulus called "onset-offset" which reflected static color stimuli and "sustained moving" without abrupt mode which reflected dynamic color stimuli to evoke event-related brain potentials (ERPs) in primary color amblyopia patients (abnormal group) and subjects with normal color recognition ability (normal group). ERPs were recorded by Neuroscan system. The results showed that in the normal group, ERPs in response to the dynamic red stimulus showed frontal positive amplitudes with a latency of about 180 ms, a negative peak at about 240 ms and a peak latency of the late positive potential (LPP) in a time window between 290 and 580 ms. In the abnormal group, ERPs in response to the dynamic red stimulus were fully lost and characterized by vanished amplitudes between 0 and 800 ms. No significant difference was noted in ERPs in response to the dynamic green and blue stimulus between the two groups (P>0.05). ERPs of the two groups in response to the static red, green and blue stimulus were not much different, showing a transient negative peak at about 170 ms and a peak latency of LPP in a time window between 350 and 650 ms. Our results first revealed that some subjects who were not identified as color blindness under static color recognition could not completely apperceive a sort of dynamic red stimulus by ERPs, which was called "dynamic red blindness". Furthermore, these results also indicated that low-frequency ERPs induced by "sustained moving" may be a good and new method to test dynamic color perception competence.
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Neurosurgical applications of ion beams
NASA Astrophysics Data System (ADS)
Fabrikant, Jacob I.; Levy, Richard P.; Phillips, Mark H.; Frankel, Kenneth A.; Lyman, John T.
1989-04-01
The program at Donner Pavilion has applied nuclear medicine research to the diagnosis and radiosurgical treatment of life-threatening intracranial vascular disorders that affect more than half a million Americans. Stereotactic heavy-charged-particle Bragg peak radiosurgery, using narrow beams of heavy ions, demonstrates superior biological and physical characteristics in brain over X-and γ-rays, viz., improved dose distribution in the Bragg peak and sharp lateral and distal borders and less scattering of the beam. Examination of CNS tissue response and alteration of cerebral blood-flow dynamics related to heavy-ion Bragg peak radiosurgery is carried out using three-dimensional treatment planning and quantitative imaging utilizing cerebral angiography, computerized tomography (CT), magnetic resonance imaging (MRI), cine-CT, xenon X-ray CT and positron emission tomography (PET). Also under examination are the physical properties of narrow heavy-ion beams for improving methods of dose delivery and dose distribution and for establishing clinical RBE/LET and dose-response relationships for human CNS tissues. Based on the evaluation and treatment with stereotactically directed narrow beams of heavy charged particles of over 300 patients, with cerebral angiography, CT scanning and MRI and PET scanning of selected patients, plus extensive clinical and neuroradiological followup, it appears that Stereotactic charged-particle Bragg peak radiosurgery obliterates intracranial arteriovenous malformations or protects against rebleeding with reduced morbidity and no mortality. Discussion will include the method of evaluation, the clinical research protocol, the Stereotactic neuroradiological preparation, treatment planning, the radiosurgery procedure and the protocol for followup. Emphasis will be placed on the neurological results, including the neuroradiological and clinical response and early and late delayed injury in brain leading to complications (including vasogenic edema, arterial occlusion, venous thrombosis and radiation necrosis). Clinical results in both children and adults will be illustrated and health outcome will be related to the advantages of charged-particle treatment planning, the radiosurgical procedure, dose distribution and dose localization.
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The effects of exercise on cardiovascular biomarkers in patients with chronic heart failure.
Ahmad, Tariq; Fiuzat, Mona; Mark, Daniel B; Neely, Ben; Neely, Megan; Kraus, William E; Kitzman, Dalane W; Whellan, David J; Donahue, Mark; Zannad, Faiez; Piña, Ileana L; Adams, Kirkwood; O'Connor, Christopher M; Felker, G Michael
2014-02-01
Exercise training is recommended for chronic heart failure (HF) patients to improve functional status and reduce risk of adverse outcomes. Elevated plasma levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cardiac troponin T (cTnT) are associated with increased risk of adverse outcomes in this patient population. Whether exercise training leads to improvements in biomarkers and how such improvements relate to clinical outcomes are unclear. Amino-terminal pro-brain natriuretic peptide, hs-CRP, and cTnT levels were assessed at baseline and 3 months in a cohort of 928 subjects from the HF-ACTION study, a randomized clinical trial of exercise training versus usual care in chronic HF patients with reduced left ventricular ejection fraction (<35%). Linear and logistic regressions were used to assess 3-month biomarker levels as a function of baseline value, treatment assignment (exercise training vs usual care), and volume of exercise. Linear regression and Cox proportional hazard modeling were used to evaluate the relations between changes in biomarker levels and clinical outcomes of interest that included change in peak oxygen consumption (peak VO2), hospitalizations, and mortality. Exercise training was not associated with significant changes in levels of NT-proBNP (P = .10), hs-CRP (P = .80), or detectable cTnT levels (P = .83) at 3 months. Controlling for baseline biomarker levels or volume of exercise did not alter these findings. Decreases in plasma concentrations of NT-proBNP, but not hs-CRP or cTnT, were associated with increases in peak VO2 (P < .001) at 3 months and decreased risk of hospitalizations or mortality (P ≤ .04), even after adjustment for a comprehensive set of known predictors. Exercise training did not lead to meaningful changes in biomarkers of myocardial stress, inflammation, or necrosis in patients with chronic HF. Only improvements in NT-proBNP translated to reductions in peak VO2 and reduced risk of clinical events. © 2014.
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Roggeveen, Suzanne; van Os, Jim; Lousberg, Richel
2015-01-01
This study aimed to investigate whether third generation mobile phone radiation peaks result in event related potentials. Thirty-one healthy females participated. In this single-blind, cross-over design, a 15 minute mobile phone exposure was compared to two 15 minute sham phone conditions, one preceding and one following the exposure condition. Each participant was measured on two separate days, where mobile phone placement was varied between the ear and heart. EEG activity and radiofrequency radiation were recorded jointly. Epochs of 1200ms, starting 200ms before and lasting until 1000ms after the onset of a radiation peak, were extracted from the exposure condition. Control epochs were randomly selected from the two sham phone conditions. The main a-priori hypothesis to be tested concerned an increase of the area in the 240-500ms post-stimulus interval, in the exposure session with ear-placement. Using multilevel regression analyses the placement*exposure interaction effect was significant for the frontal and central cortical regions, indicating that only in the mobile phone exposure with ear-placement an enlarged cortical reactivity was found. Post-hoc analyses based on visual inspection of the ERPs showed a second significantly increased area between 500-1000ms post-stimulus for almost every EEG location measured. It was concluded that, when a dialing mobile phone is placed on the ear, its radiation, although unconsciously, is electrically detected by the brain. The question of whether or not this cortical reactivity results in a negative health outcome has to be answered in future longitudinal experiments. PMID:25962168
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Roggeveen, Suzanne; van Os, Jim; Lousberg, Richel
2015-01-01
This study aimed to investigate whether third generation mobile phone radiation peaks result in event related potentials. Thirty-one healthy females participated. In this single-blind, cross-over design, a 15 minute mobile phone exposure was compared to two 15 minute sham phone conditions, one preceding and one following the exposure condition. Each participant was measured on two separate days, where mobile phone placement was varied between the ear and heart. EEG activity and radiofrequency radiation were recorded jointly. Epochs of 1200 ms, starting 200 ms before and lasting until 1000 ms after the onset of a radiation peak, were extracted from the exposure condition. Control epochs were randomly selected from the two sham phone conditions. The main a-priori hypothesis to be tested concerned an increase of the area in the 240-500 ms post-stimulus interval, in the exposure session with ear-placement. Using multilevel regression analyses the placement*exposure interaction effect was significant for the frontal and central cortical regions, indicating that only in the mobile phone exposure with ear-placement an enlarged cortical reactivity was found. Post-hoc analyses based on visual inspection of the ERPs showed a second significantly increased area between 500-1000 ms post-stimulus for almost every EEG location measured. It was concluded that, when a dialing mobile phone is placed on the ear, its radiation, although unconsciously, is electrically detected by the brain. The question of whether or not this cortical reactivity results in a negative health outcome has to be answered in future longitudinal experiments.
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Are chirps better than clicks and tonebursts for evoking middle latency responses?
Atcherson, Samuel R; Moore, Page C
2014-06-01
The middle latency response (MLR) is considered a valid clinical tool for assessing the integrity of cortical and subcortical structures. Several investigators have demonstrated that a rising frequency chirp stimulus is capable of eliciting not only larger wave V amplitudes but larger MLR components as well. However, the chirp has never been specifically examined in a hemispheric electrode montage setup that is typical for neurodiagnostic application and site-of-lesion testing. The purpose of this study was to examine the effect of chirp, click, and toneburst stimuli on MLR waveform peak latency and peak-to-peak amplitude in a hemispheric electrode montage setup. This study used a repeated-measures design. A total of 10 young adult participants (3 males, 7 females) with normal hearing were recruited and had negative histories of audiologic, otologic, and neurologic involvement, and no reported language or learning difficulties. MLR latencies (Na, Pa, Nb, and Pb) and peak-to-peak amplitudes (Na-Pa, Pa-Nb, and Nb-Pb) were measured for all conditions and were statistically evaluated for left hemisphere-right ear (C3-A2) and right hemisphere-left ear (C4-A1) recordings. Statistical analyses revealed no significant difference between C3-A2 and C4-A1 peak-to-peak amplitudes; therefore, data were collapsed. Stimulus comparisons revealed that Na evoked by tonebursts were statistically prolonged compared with both chirp and click, and that both Na-Pa and Pa-Nb peak-to-peak amplitudes were statistically larger for chirps compared with both clicks and tonebursts, and for clicks compared with tonebursts. The results of this study support the hypothesis that a chirp would offer a clinical advantage to the click and toneburst in overall peak-to-peak amplitude. As expected, normal-hearing participants did not exhibit hemispheric differences when comparing C3-A2 and C4-A1 peak-to-peak amplitudes demonstrating symmetric auditory brain function. However, chirp-evoked MLRs will require further study to determine its usefulness in clinical practice. American Academy of Audiology.
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ERIC Educational Resources Information Center
Eliot, Lise
2001-01-01
Discusses the connection between brain development and human educational needs based on neuroscience research. Considers brain development from conception, including cell structure, myelination, and regional development of the brain, stressing the importance of a child's early environment and the prenatal vulnerability of the brain. (JPB)
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Developmental implications of children's brain networks and learning.
Chan, John S Y; Wang, Yifeng; Yan, Jin H; Chen, Huafu
2016-10-01
The human brain works as a synergistic system where information exchanges between functional neuronal networks. Rudimentary networks are observed in the brain during infancy. In recent years, the question of how functional networks develop and mature in children has been a hotly discussed topic. In this review, we examined the developmental characteristics of functional networks and the impacts of skill training on children's brains. We first focused on the general rules of brain network development and on the typical and atypical development of children's brain networks. After that, we highlighted the essentials of neural plasticity and the effects of learning on brain network development. We also discussed two important theoretical and practical concerns in brain network training. Finally, we concluded by presenting the significance of network training in typically and atypically developed brains.
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Rojas-Líbano, Daniel; Wimmer Del Solar, Jonathan; Aguilar-Rivera, Marcelo; Montefusco-Siegmund, Rodrigo; Maldonado, Pedro Esteban
2018-05-16
An important unresolved question about neural processing is the mechanism by which distant brain areas coordinate their activities and relate their local processing to global neural events. A potential candidate for the local-global integration are slow rhythms such as respiration. In this article, we asked if there are modulations of local cortical processing which are phase-locked to (peripheral) sensory-motor exploratory rhythms. We studied rats on an elevated platform where they would spontaneously display exploratory and rest behaviors. Concurrent with behavior, we monitored whisking through EMG and the respiratory rhythm from the olfactory bulb (OB) local field potential (LFP). We also recorded LFPs from dorsal hippocampus, primary motor cortex, primary somatosensory cortex and primary visual cortex. We defined exploration as simultaneous whisking and sniffing above 5 Hz and found that this activity peaked at about 8 Hz. We considered rest as the absence of whisking and sniffing, and in this case, respiration occurred at about 3 Hz. We found a consistent shift across all areas toward these rhythm peaks accompanying behavioral changes. We also found, across areas, that LFP gamma (70-100 Hz) amplitude could phase-lock to the animal's OB respiratory rhythm, a finding indicative of respiration-locked changes in local processing. In a subset of animals, we also recorded the hippocampal theta activity and found that occurred at frequencies overlapped with respiration but was not spectrally coherent with it, suggesting a different oscillator. Our results are consistent with the notion of respiration as a binder or integrator of activity between brain regions.
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Katzenberger, Rebeccah J.; Ganetzky, Barry; Wassarman, David A.
2016-01-01
Outcomes of traumatic brain injury (TBI) vary because of differences in primary and secondary injuries. Primary injuries occur at the time of a traumatic event, whereas secondary injuries occur later as a result of cellular and molecular events activated in the brain and other tissues by primary injuries. We used a Drosophila melanogaster TBI model to investigate secondary injuries that cause acute mortality. By analyzing mortality percentage within 24 hr of primary injuries, we previously found that age at the time of primary injuries and diet afterward affect the severity of secondary injuries. Here, we show that secondary injuries peaked in activity 1–8 hr after primary injuries. Additionally, we demonstrate that age and diet activated distinct secondary injuries in a genotype-specific manner, and that concurrent activation of age- and diet-regulated secondary injuries synergistically increased mortality. To identify genes involved in secondary injuries that cause mortality, we compared genome-wide mRNA expression profiles of uninjured and injured flies under age and diet conditions that had different mortalities. During the peak period of secondary injuries, innate immune response genes were the predominant class of genes that changed expression. Furthermore, age and diet affected the magnitude of the change in expression of some innate immune response genes, suggesting roles for these genes in inhibiting secondary injuries that cause mortality. Our results indicate that the complexity of TBI outcomes is due in part to distinct, genetically controlled, age- and diet-regulated mechanisms that promote secondary injuries and that involve a subset of innate immune response genes. PMID:27754853
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SAR Simulation with Magneto Chiral Effects for Human Head Radiated from Cellular Phones
NASA Astrophysics Data System (ADS)
Torres-Silva, H.
2008-09-01
A numerical method for a microwave signal emitted by a cellular phone, propagating in a magneto-chiral media, characterized by an extended Born-Fedorov formalism, is presented. It is shown that the use of a cell model, combined with a real model of the human head, derived from the magnetic resonance of images allows a good determination of the near fields induced in the head when the brain chirality and the battery magnetic field are considered together. The results on a 2-Dim human head model show the evolution of the specific absorption rate, (SAR coefficient) and the spatial peak specific absorption rate which are sensitives to the magneto-chiral factor, which is important in the brain layer. For GSM/PCN phones, extremely low frequency real pulsed magnetic fields (in the order of 10 to 60 milligauss) are added to the model through the whole of the user's head. The more important conclusion of our work is that the head absorption is bigger than the results for a classical model without the magneto chiral effect. Hot spots are produced due to the combination of microwave and the magnetic field produced by the phone's operation. The FDTD method was used to compute the SARs inside the MRI based head models consisting of various tissues for 1.8 GHz. As a result, we found that in the head model having more than four kinds of tissue, the localized peak SAR reaches maximum inside the head for over five tissues including skin, bone, blood and brain cells.
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Ketamine: differential neurophysiological dynamics in functional networks in the rat brain
Ahnaou, A; Huysmans, H; Biermans, R; Manyakov, N V; Drinkenburg, W H I M
2017-01-01
Recently, the N-methyl-d-aspartate-receptor (NMDAR) antagonist ketamine has emerged as a fast-onset mechanism to achieve antidepressant activity, whereas its psychomimetic, dissociative and amnestic effects have been well documented to pharmacologically model schizophrenia features in rodents. Sleep–wake architecture, neuronal oscillations and network connectivity are key mechanisms supporting brain plasticity and cognition, which are disrupted in mood disorders such as depression and schizophrenia. In rats, we investigated the dynamic effects of acute and chronic subcutaneous administration of ketamine (2.5, 5 and 10 mg kg−1) on sleep–wake cycle, multichannels network interactions assessed by coherence and phase–amplitude cross-frequency coupling, locomotor activity (LMA), cognitive information processing as reflected by the mismatch negativity-like (MMN) component of event-related brain potentials (ERPs). Acute ketamine elicited a short, lasting inhibition of rapid eye movement (REM) sleep, increased coherence in higher gamma frequency oscillations independent of LMA, altered theta-gamma phase–amplitude coupling, increased MMN peak-amplitude response and evoked higher gamma oscillations. In contrast, chronic ketamine reduced large-scale communication among cortical regions by decreasing oscillations and coherent activity in the gamma frequency range, shifted networks activity towards slow alpha rhythm, decreased MMN peak response and enhanced aberrant higher gamma neuronal network oscillations. Altogether, our data show that acute and chronic ketamine elicited differential changes in network connectivity, ERPs and event-related oscillations (EROs), supporting possible underlying alterations in NMDAR–GABAergic signaling. The findings underscore the relevance of intermittent dosing of ketamine to accurately maintain the functional integrity of neuronal networks for long-term plastic changes and therapeutic effect. PMID:28926001
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Demirkaya, K; Demirdöğen, B Can; Torun, Z Öncel; Erdem, O; Çırak, E; Tunca, Y M
2017-10-01
Mineral trioxide aggregate (MTA) is a calcium silicate dental cement used for various applications in dentistry. This study was undertaken to test whether the presence of three commercial brands of calcium silicate dental cements in the dental extraction socket of rats would affect the brain aluminium (Al) levels and oxidative stress parameters. Right upper incisor was extracted and polyethylene tubes filled with MTA Angelus, MTA Fillapex or Theracal LC, or left empty for the control group, were inserted into the extraction socket. Rats were killed 7, 30 or 60 days after operation. Brain tissues were obtained before killing. Al levels were measured by atomic absorption spectrometry. Thiobarbituric acid reactive substances (TBARS) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were determined using spectrophotometry. A transient peak was observed in brain Al level of MTA Angelus group on day 7, while MTA Fillapex and Theracal LC groups reached highest brain Al level on day 60. Brain TBARS level, CAT, SOD and GPx activities transiently increased on day 7 and then returned to almost normal levels. This in vivo study for the first time indicated that initial washout may have occurred in MTA Angelus, while element leaching after the setting is complete may have taken place for MTA Fillapex and Theracal LC. Moreover, oxidative stress was induced and antioxidant enzymes were transiently upregulated. Further studies to search for oxidative neuronal damage should be done to completely understand the possible toxic effects of calcium silicate cements on the brain.
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Sun, Deqing; Xue, Aiying; Zhang, Bin; Lou, Haiyan; Shi, Huanying; Zhang, Xiumei
2015-12-01
Acetylpuerarin (AP) is an acetylated derivative of puerarin (PUE). The study aimed to prepare polysorbate 80-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles to improve the permeability of AP across the blood-brain barrier (BBB) and enhance its brain-protective effects. AP-loaded PLGA nanoparticles (AP-PLGA-NPs) were prepared using a solvent diffusion methodology. The NPs were characterized. The pharmacokinetics, tissue distributions and brain-protective effects of AP-PLGA-NPs were evaluated in animals. AP-PLGA-NPs were successfully prepared with a mean particle size of 145.0 nm and a zeta potential of -14.81 mV. The in-vitro release of AP from the PLGA-NPs showed a biphasic release profile. AP was metabolized into PUE in rats. The AUC0-∞ values of AP and PUE for AP-PLGA-NPs were 2.90- and 2.29-fold as great as those for AP solution, respectively. The values of the relative targeting efficiency in the brain were 2.40 and 2.58 for AP and PUE, and the ratios of peak concentration were 1.91 and 1.89 for AP and PUE, respectively. Compared with the crude drug, AP-PLGA-NPs showed better brain-protective effects in rats. Polysorbate 80-coated PLGA-NPs can improve the permeability of AP cross the BBB and enhance its brain-protective effects in rats. © 2015 Royal Pharmaceutical Society.
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Imaging brain development: the adolescent brain.
Blakemore, Sarah-Jayne
2012-06-01
The past 15 years have seen a rapid expansion in the number of studies using neuroimaging techniques to investigate maturational changes in the human brain. In this paper, I review MRI studies on structural changes in the developing brain, and fMRI studies on functional changes in the social brain during adolescence. Both MRI and fMRI studies point to adolescence as a period of continued neural development. In the final section, I discuss a number of areas of research that are just beginning and may be the subject of developmental neuroimaging in the next twenty years. Future studies might focus on complex questions including the development of functional connectivity; how gender and puberty influence adolescent brain development; the effects of genes, environment and culture on the adolescent brain; development of the atypical adolescent brain; and implications for policy of the study of the adolescent brain. Copyright © 2011 Elsevier Inc. All rights reserved.
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Sebastiani, Anne; Granold, Matthias; Ditter, Anja; Sebastiani, Philipp; Gölz, Christina; Pöttker, Bruno; Luh, Clara; Schaible, Eva-Verena; Radyushkin, Konstantin; Timaru-Kast, Ralph; Werner, Christian; Schäfer, Michael K; Engelhard, Kristin; Moosmann, Bernd; Thal, Serge C
2016-02-01
The gamma-aminobutyric acid modulator propofol induces neuronal cell death in healthy immature brains by unbalancing neurotrophin homeostasis via p75 neurotrophin receptor signaling. In adulthood, p75 neurotrophin receptor becomes down-regulated and propofol loses its neurotoxic effect. However, acute brain lesions, such as traumatic brain injury, reactivate developmental-like programs and increase p75 neurotrophin receptor expression, probably to foster reparative processes, which in turn could render the brain sensitive to propofol-mediated neurotoxicity. This study investigates the influence of delayed single-bolus propofol applications at the peak of p75 neurotrophin receptor expression after experimental traumatic brain injury in adult mice. Randomized laboratory animal study. University research laboratory. Adult C57BL/6N and nerve growth factor receptor-deficient mice. Sedation by IV propofol bolus application delayed after controlled cortical impact injury. Propofol sedation at 24 hours after traumatic brain injury increased lesion volume, enhanced calpain-induced αII-spectrin cleavage, and increased cell death in perilesional tissue. Thirty-day postinjury motor function determined by CatWalk (Noldus Information Technology, Wageningen, The Netherlands) gait analysis was significantly impaired in propofol-sedated animals. Propofol enhanced pro-brain-derived neurotrophic factor/brain-derived neurotrophic factor ratio, which aggravates p75 neurotrophin receptor-mediated cell death. Propofol toxicity was abolished both by pharmacologic inhibition of the cell death domain of the p75 neurotrophin receptor (TAT-Pep5) and in mice lacking the extracellular neurotrophin binding site of p75 neurotrophin receptor. This study provides first evidence that propofol sedation after acute brain lesions can have a deleterious impact and implicates a role for the pro-brain-derived neurotrophic factor-p75 neurotrophin receptor pathway. This observation is important as sedation with propofol and other compounds with GABA receptor activity are frequently used in patients with acute brain pathologies to facilitate sedation or surgical and interventional procedures.
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Mohamed, J Shaik; Benninghoff, Abby D; Holt, G Joan; Khan, Izhar A
2007-02-01
The cDNAs of the G protein-coupled receptor 54 (GPR54) and three prepro-gonadotropin-releasing hormones, GnRH-I (seabream GnRH), GnRH-II (chicken GnRH-II), and GnRH-III (salmon GnRH) were isolated and cloned from the brain of the teleost fish cobia, Rachycentron canadum. The cobia GPR54 cDNA was 95 and 51-56% identical to those of tilapia and mammalian models respectively. The GnRH cDNA sequences of cobia showed strong identities to those of tilapia, Atlantic croaker, red drum, and the seabass and seabream species. The real-time quantitative RT-PCR methods allowed detection of all three GnRH mRNAs on the first day after hatching (DAH). The GnRH-I mRNA levels, which were the lowest among the three GnRHs, increased gradually with two distinct peaks in larvae at 3 and 4 DAH. On the other hand, GnRH-II and GnRH-III mRNAs were significantly higher in larvae at 2 and 6 DAH compared with those on the preceding days. In addition, significant peaks of all the three GnRH mRNAs were observed in the brains of 26-day-old fish. The finding of higher GnRH-I and GnRH-II mRNAs in males than females at 153 DAH may be related to early puberty observed during the first year in laboratory-reared male cobia. Moreover, this study demonstrates for the first time the expression of GPR54 mRNA during larval development in a vertebrate species. The concomitant expression patterns of GPR54 and GnRH mRNAs during different stages of larval and juvenile developments, and during early puberty in male cobia suggest a potential relationship between GPR54 and multiple GnRHs during these stages of development consistent with the role of GPR54 in controlling GnRH release in mammals. The increase in GPR54 and GnRH mRNAs observed during early puberty in cobia is consistent with a similar change reported in pubertal rats. This finding together with the localization of GPR54 mRNAs on GnRH neurons in fish and mammals suggests that the GPR54-GnRH interactions may be conserved in different vertebrate groups.
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Gillick, Bernadette T.; Kirton, Adam; Carmel, Jason B.; Minhas, Preet; Bikson, Marom
2014-01-01
Background: Transcranial direct current stimulation (tDCS) has been investigated mainly in adults and doses may not be appropriate in pediatric applications. In perinatal stroke where potential applications are promising, rational adaptation of dosage for children remains under investigation. Objective: Construct child-specific tDCS dosing parameters through case study within a perinatal stroke tDCS safety and feasibility trial. Methods: 10-year-old subject with a diagnosis of presumed perinatal ischemic stroke and hemiparesis was identified. T1 magnetic resonance imaging (MRI) scans used to derive computerized model for current flow and electrode positions. Workflow using modeling results and consideration of dosage in previous clinical trials was incorporated. Prior ad hoc adult montages vs. de novo optimized montages provided distinct risk benefit analysis. Approximating adult dose required consideration of changes in both peak brain current flow and distribution which further tradeoff between maximizing efficacy and adding safety factors. Electrode size, position, current intensity, compliance voltage, and duration were controlled independently in this process. Results: Brain electric fields modeled and compared to values previously predicted models (Datta et al., 2011; Minhas et al., 2012). Approximating conservative brain current flow patterns and intensities used in previous adult trials for comparable indications, the optimal current intensity established was 0.7 mA for 10 min with a tDCS C3/C4 montage. Specifically 0.7 mA produced comparable peak brain current intensity of an average adult receiving 1.0 mA. Electrode size of 5 × 7 cm2 with 1.0 mA and low-voltage tDCS was employed to maximize tolerability. Safety and feasibility confirmed with subject tolerating the session well and no serious adverse events. Conclusion: Rational approaches to dose customization, with steps informed by computational modeling, may improve guidance for pediatric stroke tDCS trials. PMID:25285077
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Ross, Matthew K; Jones, Toni L; Filipov, Nikolay M
2009-04-01
2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine (atrazine, ATR) is a toxicologically important and widely used herbicide. Recent studies have shown that it can elicit neurological, immunological, developmental, and biochemical alterations in several model organisms, including in mice. Because disposition data in mice are lacking, we evaluated ATR's metabolism and tissue dosimetry after single oral exposures (5-250 mg/kg) in C57BL/6 mice using liquid chromatography/mass spectrometry (Ross and Filipov, 2006). ATR was metabolized and cleared rapidly; didealkyl ATR (DACT) was the major metabolite detected in urine, plasma, and tissues. Plasma ATR peaked at 1 h postdosing and rapidly declined, whereas DACT peaked at 2 h and slowly declined. Most ATR and metabolite residues were excreted within the first 24 h. However, substantial amounts of DACT were still present in 25- to 48-h and 49- to 72-h urine. ATR reached maximal brain levels (0.06-1.5 microM) at 4 h (5-125 mg/kg) and 1 h (250 mg/kg) after dosing, but levels quickly declined to <0.1 microM by 12 h in all the groups. In contrast, strikingly high concentrations of DACT (1.5-50 microM), which are comparable with liver DACT levels, were detectable in brain at 2 h. Brain DACT levels slowly declined, paralleling the kinetics of plasma DACT. Our findings suggest that in mice ATR is widely distributed and extensively metabolized and that DACT is a major metabolite detected in the brain at high levels and is ultimately excreted in urine. Our study provides a starting point for the establishment of models that link target tissue dose to biological effects caused by ATR and its in vivo metabolites.
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Oscillatory motor network activity during rest and movement: an fNIRS study
Bajaj, Sahil; Drake, Daniel; Butler, Andrew J.; Dhamala, Mukesh
2014-01-01
Coherent network oscillations (<0.1 Hz) linking distributed brain regions are commonly observed in the brain during both rest and task conditions. What oscillatory network exists and how network oscillations change in connectivity strength, frequency and direction when going from rest to explicit task are topics of recent inquiry. Here, we study network oscillations within the sensorimotor regions of able-bodied individuals using hemodynamic activity as measured by functional near-infrared spectroscopy (fNIRS). Using spectral interdependency methods, we examined how the supplementary motor area (SMA), the left premotor cortex (LPMC) and the left primary motor cortex (LM1) are bound as a network during extended resting state (RS) and between-tasks resting state (btRS), and how the activity of the network changes as participants execute left, right, and bilateral hand (LH, RH, and BH) finger movements. We found: (i) power, coherence and Granger causality (GC) spectra had significant peaks within the frequency band (0.01–0.04 Hz) during RS whereas the peaks shifted to a bit higher frequency range (0.04–0.08 Hz) during btRS and finger movement tasks, (ii) there was significant bidirectional connectivity between all the nodes during RS and unidirectional connectivity from the LM1 to SMA and LM1 to LPMC during btRS, and (iii) the connections from SMA to LM1 and from LPMC to LM1 were significantly modulated in LH, RH, and BH finger movements relative to btRS. The unidirectional connectivity from SMA to LM1 just before the actual task changed to the bidirectional connectivity during LH and BH finger movement. The uni-directionality could be associated with movement suppression and the bi-directionality with preparation, sensorimotor update and controlled execution. These results underscore that fNIRS is an effective tool for monitoring spectral signatures of brain activity, which may serve as an important precursor before monitoring the recovery progress following brain injury. PMID:24550793
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Kim, Tyson N.; Goodwill, Patrick W.; Chen, Yeni; Conolly, Steven M.; Schaffer, Chris B.; Liepmann, Dorian; Wang, Rong A.
2012-01-01
Background The ability to measure blood velocities is critical for studying vascular development, physiology, and pathology. A key challenge is to quantify a wide range of blood velocities in vessels deep within living specimens with concurrent diffraction-limited resolution imaging of vascular cells. Two-photon laser scanning microscopy (TPLSM) has shown tremendous promise in analyzing blood velocities hundreds of micrometers deep in animals with cellular resolution. However, current analysis of TPLSM-based data is limited to the lower range of blood velocities and is not adequate to study faster velocities in many normal or disease conditions. Methodology/Principal Findings We developed line-scanning particle image velocimetry (LS-PIV), which used TPLSM data to quantify peak blood velocities up to 84 mm/s in live mice harboring brain arteriovenous malformation, a disease characterized by high flow. With this method, we were able to accurately detect the elevated blood velocities and exaggerated pulsatility along the abnormal vascular network in these animals. LS-PIV robustly analyzed noisy data from vessels as deep as 850 µm below the brain surface. In addition to analyzing in vivo data, we validated the accuracy of LS-PIV up to 800 mm/s using simulations with known velocity and noise parameters. Conclusions/Significance To our knowledge, these blood velocity measurements are the fastest recorded with TPLSM. Partnered with transgenic mice carrying cell-specific fluorescent reporters, LS-PIV will also enable the direct in vivo correlation of cellular, biochemical, and hemodynamic parameters in high flow vascular development and diseases such as atherogenesis, arteriogenesis, and vascular anomalies. PMID:22761686
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Fasting and Fast Food Diet Play an Opposite Role in Mice Brain Aging.
Castrogiovanni, Paola; Li Volti, Giovanni; Sanfilippo, Cristina; Tibullo, Daniele; Galvano, Fabio; Vecchio, Michele; Avola, Roberto; Barbagallo, Ignazio; Malaguarnera, Lucia; Castorina, Sergio; Musumeci, Giuseppe; Imbesi, Rosa; Di Rosa, Michelino
2018-01-20
Fasting may be exploited as a possible strategy for prevention and treatment of several diseases such as diabetes, obesity, and aging. On the other hand, high-fat diet (HFD) represents a risk factor for several diseases and increased mortality. The aim of the present study was to evaluate the impact of fasting on mouse brain aging transcriptome and how HFD regulates such pathways. We used the NCBI Gene Expression Omnibus (GEO) database, in order to identify suitable microarray datasets comparing mouse brain transcriptome under fasting or HFD vs aged mouse brain transcriptome. Three microarray datasets were selected for this study, GSE24504, GSE6285, and GSE8150, and the principal molecular mechanisms involved in this process were evaluated. This analysis showed that, regardless of fasting duration, mouse brain significantly expressed 21 and 30 upregulated and downregulated genes, respectively. The involved biological processes were related to cell cycle arrest, cell death inhibition, and regulation of cellular metabolism. Comparing mouse brain transcriptome under fasting and aged conditions, we found out that the number of genes in common increased with the duration of fasting (222 genes), peaking at 72 h. In addition, mouse brain transcriptome under HFD resembles for the 30% the one of the aged mice. Furthermore, several molecular processes were found to be shared between HFD and aging. In conclusion, we suggest that fasting and HFD play an opposite role in brain transcriptome of aged mice. Therefore, an intermittent diet could represent a possible clinical strategy to counteract aging, loss of memory, and neuroinflammation. Furthermore, low-fat diet leads to the inactivation of brain degenerative processes triggered by aging.
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Tsujikawa, Tetsuya; Zoghbi, Sami S.; Hong, Jinsoo; Donohue, Sean R.; Jenko, Kimberly J.; Gladding, Robert L.; Halldin, Christer; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro
2013-01-01
We recently developed a novel cannabinoid subtype-1 (CB1) receptor radioligand 11C-SD5024 for brain imaging. This study aimed to evaluate 11C-SD5024 both in vitro and in vivo and compare it with the other CB1 receptor ligands previously used in humans, i.e., 11C-MePPEP, 11C-OMAR, 18F-MK-9470, and 18F-FMPEP-d2. In vitro experiments were performed to measure dissociation constant (Ki) in human brain and to measure the lipophilicity of five CB1 receptor ligands listed above. In vivo specific binding in monkeys was measured by comparing total distribution volume (VT) at baseline and after full receptor blockade. The kinetics of 11C-SD5024 in humans were evaluated in seven healthy subjects with compartmental modeling. SD5024 showed Ki=0.47 nM, which was at an intermediate level among the five CB1 receptor ligands. Lipophilicity (LogD7.4) was 3.79, which is appropriate for brain imaging. Monkey scans showed high proportion of specific binding: ~80% of VT. In humans, 11C-SD5024 showed peak brain uptake of 1.5–3 standardized uptake value, which was slightly higher than those of 11C-OMAR and 18F-MK-9470. One-compartment model showed good fitting, consistent with the vast majority of brain uptake being specific binding found in the monkey. Regional VT values were consistent with known distribution of CB1 receptors. VT calculated from 80 and 120 min of scan data were strongly correlated (R2=0.97), indicating that 80 min provided adequate information for quantitation and that the influence of radiometabolites was low. Intersubject variability for VT of 11C-SD5024 was 22%, which was low among the five radioligands and indicated precise measurement. In conclusion, 11C-SD5024 has appropriate affinity and lipophilicity, high specific binding, moderate brain uptake, and provides good precision to measure the binding. The results suggest that 11C-SD5024 is slightly better than or equivalent to 11C-OMAR and that both are suitable for clinical studies, especially those that involve two scans in one day. PMID:24076222
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The ERP research about the influence of the music of Chopin on working memory
NASA Astrophysics Data System (ADS)
Sun, C. A.; Wei, Hong-tao; Yue, Li-juan
2011-10-01
This study is to examine the effect of the music of Chopin on working memory and the electrical activity of the brain in different conditions by using event-related potentials (ERPs), adopting n-back experimental paradigm and to study the neuromechanism. Thirty adults performed behavioral experiments with three conditions of music and two levels of n-back task. Fourteen normal adults performed ERP experiments with the same program as the behavioral experiment and the EEG were recorded. Chopin music improved people's working memory and pilot music improved most effectively.P3 peak amplitude decreased as working memory load increased. Especially in high load task, P3 peak amplitude decreased gradually in pilot music, background music and free music condition.
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Walters, T J; Mason, P A; Sherry, C J; Steffen, C; Merritt, J H
1995-06-01
A wide range assessment of the possible bioeffects of an acute exposure to high peak power ultra-wide band (UWB) electromagnetic radiation was performed in rats. The UWB-exposure consisted of 2 min of pulsed (frequency: 60 Hz, pulse width: 5-10 ns) UWB (bandwidth: 0.25-2.50 GHz) electromagnetic radiation. Rats were examined using one of the following: 1) a functional observational battery (FOB); 2) a swimming performance test; 3) a complete panel of blood chemistries; or 4) determination of the expression of the c-fos protein in immunohistologically-stained sections of the brain. No significant differences were found between UWB- or sham-exposed rats on any of the measured parameters.
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The Evolution of Post-Traumatic Stress Disorder following Moderate-to-Severe Traumatic Brain Injury.
Alway, Yvette; Gould, Kate Rachel; McKay, Adam; Johnston, Lisa; Ponsford, Jennie
2016-05-01
Increasing evidence indicates that post-traumatic stress disorder (PTSD) may develop following traumatic brain injury (TBI), despite most patients having no conscious memory of their accident. This prospective study examined the frequency, timing of onset, symptom profile, and trajectory of PTSD and its psychiatric comorbidities during the first 4 years following moderate-to-severe TBI. Participants were 85 individuals (78.8% male) with moderate or severe TBI recruited following admission to acute rehabilitation between 2005 and 2010. Using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Disorders (SCID-I), participants were evaluated for pre- and post-injury PTSD soon after injury and reassessed at 6 months, 12 months, 2 years, 3 years, and 4 years post-injury. Over the first 4 years post-injury, 17.6% developed injury-related PTSD, none of whom had PTSD prior to injury. PTSD onset peaked between 6 and 12 months post-injury. The majority of PTSD cases (66.7%) had a delayed-onset, which for a third was preceded by subsyndromal symptoms in the first 6 months post-injury. PTSD frequency increased over the first year post-injury, remained stable during the second year, and gradually declined thereafter. The majority of subjects with PTSD experienced a chronic symptom course and all developed one or more than one comorbid psychiatric disorder, with mood, other anxiety, and substance-use disorders being the most common. Despite event-related amnesia, post-traumatic stress symptoms, including vivid re-experiencing phenomena, may develop following moderate-to-severe TBI. Onset is typically delayed and symptoms may persist for several years post-injury.
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Asemani, Davud; Morsheddost, Hassan; Shalchy, Mahsa Alizadeh
2017-06-01
Functional magnetic resonance imaging (fMRI) can generate brain images that show neuronal activity due to sensory, cognitive or motor tasks. Haemodynamic response function (HRF) may be considered as a biomarker to discriminate the Alzheimer disease (AD) from healthy ageing. As blood-oxygenation-level-dependent fMRI signal is much weak and noisy, particularly for the elderly subjects, a robust method is necessary for HRF estimation to efficiently differentiate the AD. After applying minimum description length wavelet as an extra denoising step, deconvolution algorithm is here employed for HRF estimation, substituting the averaging method used in the previous works. The HRF amplitude peaks are compared for three groups HRF of young, non-demented and demented elderly groups for both vision and motor regions. Prior works often reported significant differences in the HRF peak amplitude between the young and the elderly. The authors' experimentations show that the HRF peaks are not significantly different comparing the young adults with the elderly (either demented or non-demented). It is here demonstrated that the contradictory findings of the previous studies on the HRF peaks for the elderly compared with the young are originated from the noise contribution in fMRI data.
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Li, Shizhe; An, Li; Yu, Shao; Ferraris Araneta, Maria; Johnson, Christopher S; Wang, Shumin; Shen, Jun
2016-03-01
Carbon-13 ((13)C) MR spectroscopy (MRS) of the human brain at 7 Tesla (T) may pose patient safety issues due to high radiofrequency (RF) power deposition for proton decoupling. The purpose of present work is to study the feasibility of in vivo (13)C MRS of human brain at 7 T using broadband low RF power proton decoupling. Carboxylic/amide (13)C MRS of human brain by broadband stochastic proton decoupling was demonstrated on a 7 T scanner. RF safety was evaluated using the finite-difference time-domain method. (13)C signal enhancement by nuclear Overhauser effect (NOE) and proton decoupling was evaluated in both phantoms and in vivo. At 7 T, the peak amplitude of carboxylic/amide (13)C signals was increased by a factor of greater than 4 due to the combined effects of NOE and proton decoupling. The 7 T (13)C MRS technique used decoupling power and average transmit power of less than 35 watts (W) and 3.6 W, respectively. In vivo (13)C MRS studies of human brain can be performed at 7 T, well below the RF safety threshold, by detecting carboxylic/amide carbons with broadband stochastic proton decoupling. © 2015 Wiley Periodicals, Inc.
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Distribution of RF energy emitted by mobile phones in anatomical structures of the brain.
Cardis, E; Deltour, I; Mann, S; Moissonnier, M; Taki, M; Varsier, N; Wake, K; Wiart, J
2008-06-07
The rapid worldwide increase in mobile phone use in the last decade has generated considerable interest in possible carcinogenic effects of radio frequency (RF). Because exposure to RF from phones is localized, if a risk exists it is likely to be greatest for tumours in regions with greatest energy absorption. The objective of the current paper was to characterize the spatial distribution of RF energy in the brain, using results of measurements made in two laboratories on 110 phones used in Europe or Japan. Most (97-99% depending on frequency) appears to be absorbed in the brain hemisphere on the side where the phone is used, mainly (50-60%) in the temporal lobe. The average relative SAR is highest in the temporal lobe (6-15%, depending on frequency, of the spatial peak SAR in the most exposed region of the brain) and the cerebellum (2-10%) and decreases very rapidly with increasing depth, particularly at higher frequencies. The SAR distribution appears to be fairly similar across phone models, between older and newer phones and between phones with different antenna types and positions. Analyses of risk by location of tumour are therefore important for the interpretation of results of studies of brain tumours in relation to mobile phone use.
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Brain activation in parietal area during manipulation with a surgical robot simulator.
Miura, Satoshi; Kobayashi, Yo; Kawamura, Kazuya; Nakashima, Yasutaka; Fujie, Masakatsu G
2015-06-01
we present an evaluation method to qualify the embodiment caused by the physical difference between master-slave surgical robots by measuring the activation of the intraparietal sulcus in the user's brain activity during surgical robot manipulation. We show the change of embodiment based on the change of the optical axis-to-target view angle in the surgical simulator to change the manipulator's appearance in the monitor in terms of hand-eye coordination. The objective is to explore the change of brain activation according to the change of the optical axis-to-target view angle. In the experiments, we used a functional near-infrared spectroscopic topography (f-NIRS) brain imaging device to measure the brain activity of the seven subjects while they moved the hand controller to insert a curved needle into a target using the manipulator in a surgical simulator. The experiment was carried out several times with a variety of optical axis-to-target view angles. Some participants showed a significant peak (P value = 0.037, F-number = 2.841) when the optical axis-to-target view angle was 75°. The positional relationship between the manipulators and endoscope at 75° would be the closest to the human physical relationship between the hands and eyes.
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Li, Shizhe; An, Li; Yu, Shao; Araneta, Maria Ferraris; Johnson, Christopher S.; Wang, Shumin; Shen, Jun
2015-01-01
Purpose 13C magnetic resonance spectroscopy (MRS) of human brain at 7 Tesla (T) may pose patient safety issues due to high RF power deposition for proton decoupling. The purpose of present work is to study the feasibility of in vivo 13C MRS of human brain at 7 T using broadband low RF power proton decoupling. Methods Carboxylic/amide 13C MRS of human brain by broadband stochastic proton decoupling was demonstrated on a 7 T scanner. RF safety was evaluated using the finite-difference time-domain method. 13C signal enhancement by nuclear Overhauser effect (NOE) and proton decoupling was evaluated in both phantoms and in vivo. Results At 7 T, the peak amplitude of carboxylic/amide 13C signals was increased by a factor of greater than 4 due to the combined effects of NOE and proton decoupling. The 7 T 13C MRS technique used decoupling power and average transmit power of less than 35 W and 3.6 W, respectively. Conclusion In vivo 13C MRS studies of human brain can be performed at 7 T well below the RF safety threshold by detecting carboxylic/amide carbons with broadband stochastic proton decoupling. PMID:25917936
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Studying the Brain in a Dish: 3D Cell Culture Models of Human Brain Development and Disease.
Brown, Juliana; Quadrato, Giorgia; Arlotta, Paola
2018-01-01
The study of the cellular and molecular processes of the developing human brain has been hindered by access to suitable models of living human brain tissue. Recently developed 3D cell culture models offer the promise of studying fundamental brain processes in the context of human genetic background and species-specific developmental mechanisms. Here, we review the current state of 3D human brain organoid models and consider their potential to enable investigation of complex aspects of human brain development and the underpinning of human neurological disease. © 2018 Elsevier Inc. All rights reserved.
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Inouye, M; Yamamura, H; Nakano, A
1995-09-01
Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 mumol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 micrograms/g at the time of irradiation and remaining at more than 40 micrograms/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositidemediated signaling systems regulate radiation-induced apoptosis.
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Age-related changes in dopamine signaling in Nurr1 deficient mice as a model of Parkinson’s disease
Zhang, Lifen; Le, Weidong; Xie, Wenjie; Dani, John A.
2011-01-01
The nuclear receptor related 1 (Nurr1) transcription factor contributes to the development and maintenance of dopamine (DA) neurons in the brain. We found that heterozygous Nurr1 knock-out (Nurr1 +/−) influenced the age-dependent decline in the number of DA neurons and influenced DA signaling. We examined the DA marker, tyrosine hydroxylase, using immunohistochemistry, and we measured DA signaling using fast-scan cyclic voltammetry in 3 age groups of wild-type (Nurr1 +/+) and mutant (Nurr1 +/−) mice: 3–6, 9–12, and 15–23 months old. Prior to significant loss of DA neurons and to the onset of parkinsonian symptoms, young Nurr1 +/− mice (3–6 months) exhibited a decrease in peak evoked DA release that was partially countered by a decrease in the rate of DA reuptake. As peak evoked DA release declined with age for both the wild-type and Nurr1 +/− mice, both genotypes manifested decreased DA reuptake. As the DA release fell further with age, decreased DA reuptake eventually could not adequately compensate the Nurr1 +/− mice. The results indicated that Nurr1 deficiency led to impaired DA release even before significant DA neuron loss. PMID:21531044
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ERIC Educational Resources Information Center
Marsh, Rachel; Gerber, Andrew J.; Peterson, Bradley S.
2008-01-01
Neuroimaging findings which identify normal brain development trajectories are presented. Results show that early brain development begins with the neural tube formation and ends with myelintation. How disturbances in brain development patterns are related to childhood psychiatric disorders is examined.
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Saeedi, Alireza; Jannesari, Mostafa; Gharibzadeh, Shahriar; Bakouie, Fatemeh
2018-04-01
Self-organized criticality (SOC) and stochastic oscillations (SOs) are two theoretically contradictory phenomena that are suggested to coexist in the brain. Recently it has been shown that an accumulation-release process like sandpile dynamics can generate SOC and SOs simultaneously. We considered the effect of the network structure on this coexistence and showed that the sandpile dynamics on a small-world network can produce two power law regimes along with two groups of SOs-two peaks in the power spectrum of the generated signal simultaneously. We also showed that external stimuli in the sandpile dynamics do not affect the coexistence of SOC and SOs but increase the frequency of SOs, which is consistent with our knowledge of the brain.
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NASA Astrophysics Data System (ADS)
Lanin, Aleksandr A.; Fedotov, Il'ya V.; Sidorov-Biryukov, Dmitrii A.; Doronina-Amitonova, Lyubov V.; Ivashkina, Olga I.; Zots, Marina A.; Sun, Chi-Kuang; Ömer Ilday, F.; Fedotov, Andrei B.; Anokhin, Konstantin V.; Zheltikov, Aleksei M.
2012-03-01
Large-core hollow photonic-crystal fibers (PCFs) are shown to enable a fiber-format air-guided delivery of ultrashort infrared laser pulses for neurosurgery and nonlinear-optical imaging. With an appropriate dispersion precompensation, an anomalously dispersive 15-μm-core hollow PCF compresses 510-fs, 1070-nm light pulses to a pulse width of about 110 fs, providing a peak power in excess of 5 MW. The compressed PCF output is employed to induce a local photodisruption of corpus callosum tissues in mouse brain and is used to generate the third harmonic in brain tissues, which is captured by the PCF and delivered to a detector through the PCF cladding.
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Metabolic alterations in developing brain after injury – knowns and unknowns
McKenna, Mary C.; Scafidi, Susanna; Robertson, Courtney L.
2016-01-01
Brain development is a highly orchestrated complex process. The developing brain utilizes many substrates including glucose, ketone bodies, lactate, fatty acids and amino acids for energy, cell division and the biosynthesis of nucleotides, proteins and lipids. Metabolism is crucial to provide energy for all cellular processes required for brain development and function including ATP formation, synaptogenesis, synthesis, release and uptake of neurotransmitters, maintaining ionic gradients and redox status, and myelination. The rapidly growing population of infants and children with neurodevelopmental and cognitive impairments and life-long disability resulting from developmental brain injury is a significant public health concern. Brain injury in infants and children can have devastating effects because the injury is superimposed on the high metabolic demands of the developing brain. Acute injury in the pediatric brain can derail, halt or lead to dysregulation of the complex and highly regulated normal developmental processes. This paper provides a brief review of metabolism in developing brain and alterations found clinically and in animal models of developmental brain injury. The metabolic changes observed in three major categories of injury that can result in life-long cognitive and neurological disabilities, including neonatal hypoxia-ischemia, pediatric traumatic brain injury, and brain injury secondary to prematurity are reviewed. PMID:26148530
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Usende, Ifukibot Levi; Leitner, Dominque F; Neely, Elizabeth; Connor, James R; Olopade, James O
2016-08-30
Oligodendrocyte development and myelination occurs vigorously during the early post natal period which coincides with the period of peak mobilization of iron. Oligodendrocyte progenitor cells (OPCs) are easily disturbed by any agent that affects iron homeostasis and its assimilation into these cells. Environmental exposure to vanadium, a transition metal can disrupt this iron homeostasis. We investigated the interaction of iron deficiency and vanadium exposure on the myelination infrastructure and its related neurobehavioural phenotypes, and neurocellular profiles in developing rat brains. Control group (C) dams were fed normal diet while Group 2 (V) dams were fed normal diet and pups were injected with 3mg/kg body weight of sodium metavanadate daily from postnatal day (PND) 1-21. Group 3 (I+V) dams were fed iron deficient diet after delivery and pups injected with 3mg/kg body weight sodium metavanadate from PND1-21. Body and brain weights deteriorated in I+V relative to C and V while neurobehavioral deficit occurred more in V. Whereas immunohistochemical staining shows more astrogliosis and microgliosis indicative of neuroinflammation in I+V, more intense OPCs depletion and hypomyelination were seen in the V, and this was partially protected in I+V. In in vitro studies, vanadium induced glial cells toxicity was partially protected only at the LD 50 dose with the iron chelator, desferroxamine. The data indicate that vanadium promotes myelin damage and iron deficiency in combination with vanadium partially protects this neurotoxicological effects of vanadium.
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Brain anatomical networks in early human brain development.
Fan, Yong; Shi, Feng; Smith, Jeffrey Keith; Lin, Weili; Gilmore, John H; Shen, Dinggang
2011-02-01
Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1 month, 1 year, and 2 years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1 year and 2 years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information. Copyright © 2010. Published by Elsevier Inc.