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  1. NeuroSPECT demonstrates increased cortical function in Alzheimer's disease patients for at least two years after omental transposition neurosurgery

    International Nuclear Information System (INIS)

    Shankle, William R; Mena, Ismael; Hara, Junko; O'Heany, Terence; Bjornsen, Lynda; Gade, George; Leport, Peter; Ali, Mir; Rayhaun, Abraham; Kim, Jinho; Malkazian, Dennis; Raimo, Maryellen; Reyes, Linda; Fallon, James; Kim, Ronald

    2006-01-01

    Clinical improvement following surgical transposition of the omentum to the brain (OTS) has been observed in a variety of neurologic disorders, including stroke, encephalitis, cerebral palsy, spinal cord transaction and Alzheimer's disease. The basis for such improvement is not known, but may relate to the presence of stem cells and growth factors in the omentum, which have been implicated in angiogenesis, neurogenesis and neuronal survival. The present report describes the changes in brain activity in two patients with biopsy confirmed Alzheimer's disease (AD) whose course had entered a phase of more rapid decline prior to OTS. The patients were followed with disease severity (Clinical Dementia Rating Scale), cognitive (Mini-Mental Status Exam) and HMPAO NeuroSPECT measures for 22 and 42 months. Dementia severity lessened for 2 or more years while cortical activity in areas underneath, adjacent to, and contralateral to the omentum increased by 1-2 standard deviations above the patient's preoperative baseline (maximum increase was 21%, 4 Standard Deviations). In the more mildly demented AD patient 22 months after OTS, the posterior cingulate cortex showed up to a 20% increase in activity compared to is preoperative level of activity. This is remarkable in that the omentum had no direct contact with the posterior cingulate gyrus, which is involved in the early stages of AD neuropathology (Braak and Braak stages 3-4). These findings warrant further investigation into the mechanism(s) by which the omentum can improve cortical activity and clinical function for two or more years in Alzheimers' disease (au)

  2. Mesenchymal stem cells from cortical bone demonstrate increased clonal incidence, potency, and developmental capacity compared to their bone marrow–derived counterparts

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    Daniel Blashki

    2016-08-01

    Full Text Available In this study, we show that matrix dense cortical bone is the more potent compartment of bone than bone marrow as a stromal source for mesenchymal stem cells as isolated from adult rats. Lineage-depleted cortical bone-mesenchymal stem cells demonstrated >150-fold enrichment of colony forming unit–fibroblasts per cell incidence. compared to lineage-depleted bone marrow-mesenchymal stem cells, corresponding to a 70-fold increase in absolute recovered colony forming unit–fibroblasts. The composite phenotype Lin−/CD45−/CD31−/VLA-1+/Thy-1+ enriched for clonogenic mesenchymal stem cells solely from cortical bone–derived cells from which 70% of clones spontaneously differentiated into all lineages of bone, cartilage, and adipose. Both populations generated vascularized bone tissue within subcutaneous implanted collagen scaffolds; however, cortical bone–derived cells formed significantly more osteoid than bone marrow counterparts, quantified by histology. The data demonstrate that our isolation protocol identifies and validates mesenchymal stem cells with superior clonal, proliferative, and developmental potential from cortical bone compared to the bone marrow niche although marrow persists as the typical source for mesenchymal stem cells both in the literature and current pre-clinical therapies.

  3. Tactile thermal oral stimulation increases the cortical representation of swallowing

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    Suntrup Sonja

    2009-06-01

    Full Text Available Abstract Background Dysphagia is a leading complication in stroke patients causing aspiration pneumonia, malnutrition and increased mortality. Current strategies of swallowing therapy involve on the one hand modification of eating behaviour or swallowing technique and on the other hand facilitation of swallowing with the use of pharyngeal sensory stimulation. Thermal tactile oral stimulation (TTOS is an established method to treat patients with neurogenic dysphagia especially if caused by sensory deficits. Little is known about the possible mechanisms by which this interventional therapy may work. We employed whole-head MEG to study changes in cortical activation during self-paced volitional swallowing in fifteen healthy subjects with and without TTOS. Data were analyzed by means of synthetic aperture magnetometry (SAM and the group analysis of individual SAM data was performed using a permutation test. Results Compared to the normal swallowing task a significantly increased bilateral cortical activation was seen after oropharyngeal stimulation. Analysis of the chronological changes during swallowing suggests facilitation of both the oral and the pharyngeal phase of deglutition. Conclusion In the present study functional cortical changes elicited by oral sensory stimulation could be demonstrated. We suggest that these results reflect short-term cortical plasticity of sensory swallowing areas. These findings facilitate our understanding of the role of cortical reorganization in dysphagia treatment and recovery.

  4. Right-frontal cortical asymmetry predicts increased proneness to nostalgia.

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    Tullett, Alexa M; Wildschut, Tim; Sedikides, Constantine; Inzlicht, Michael

    2015-08-01

    Nostalgia is often triggered by feelings-such as sadness, loneliness, or meaninglessness-that are typically associated with withdrawal motivation. Here, we examined whether a trait tendency to experience withdrawal motivation is associated with nostalgia proneness. Past work indicates that baseline right-frontal cortical asymmetry is a neural correlate of withdrawal-related motivation. We therefore hypothesized that higher baseline levels of right-frontal asymmetry would predict increased proneness to nostalgia. We assessed participants' baseline levels of frontal cortical activity using EEG. Results supported the hypothesis and demonstrated that the association between relative right-frontal asymmetry and increased nostalgia remained significant when controlling for the Big Five personality traits. Overall, these findings indicate that individuals with a stronger dispositional tendency to experience withdrawal-related motivation are more prone to nostalgia. © 2015 Society for Psychophysiological Research.

  5. Jealousy increased by induced relative left frontal cortical activity.

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    Kelley, Nicholas J; Eastwick, Paul W; Harmon-Jones, Eddie; Schmeichel, Brandon J

    2015-10-01

    Asymmetric frontal cortical activity may be one key to the process linking social exclusion to jealous feelings. The current research examined the causal role of asymmetric frontal brain activity in modulating jealousy in response to social exclusion. Transcranial direct-current stimulation (tDCS) over the frontal cortex to manipulate asymmetric frontal cortical activity was combined with a modified version of the Cyberball paradigm designed to induce jealousy. After receiving 15 min of tDCS, participants were excluded by a desired partner and reported how jealous they felt. Among individuals who were excluded, tDCS to increase relative left frontal cortical activity caused greater levels of self-reported jealousy compared to tDCS to increase relative right frontal cortical activity or sham stimulation. Limitations concerning the specificity of this effect and implications for the role of the asymmetric prefrontal cortical activity in motivated behaviors are discussed. (c) 2015 APA, all rights reserved).

  6. Increased Cortical Thickness in Professional On-Line Gamers

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    Hyun, Gi Jung; Shin, Yong Wook; Kim, Bung-Nyun; Cheong, Jae Hoon; Jin, Seong Nam

    2013-01-01

    Objective The bulk of recent studies have tested whether video games change the brain in terms of activity and cortical volume. However, such studies are limited by several factors including cross-sectional comparisons, co-morbidity, and short-term follow-up periods. In the present study, we hypothesized that cognitive flexibility and the volume of brain cortex would be correlated with the career length of on-line pro-gamers. Methods High-resolution magnetic resonance scans were acquired in twenty-three pro-gamers recruited from StarCraft pro-game teams. We measured cortical thickness in each individual using FreeSurfer and the cortical thickness was correlated with the career length and the performance of the pro-gamers. Results Career length was positively correlated with cortical thickness in three brain regions: right superior frontal gyrus, right superior parietal gyrus, and right precentral gyrus. Additionally, increased cortical thickness in the prefrontal cortex was correlated with winning rates of the pro-game league. Increased cortical thickness in the prefrontal and parietal cortices was also associated with higher performance of Wisconsin Card Sorting Test. Conclusion Our results suggest that in individuals without pathologic conditions, regular, long-term playing of on-line games is associated with volume changes in the prefrontal and parietal cortices, which are associated with cognitive flexibility. PMID:24474988

  7. Attention Increases Spike Count Correlations between Visual Cortical Areas

    Science.gov (United States)

    Cohen, Marlene R.

    2016-01-01

    Visual attention, which improves perception of attended locations or objects, has long been known to affect many aspects of the responses of neuronal populations in visual cortex. There are two nonmutually exclusive hypotheses concerning the neuronal mechanisms that underlie these perceptual improvements. The first hypothesis, that attention improves the information encoded by a population of neurons in a particular cortical area, has considerable physiological support. The second hypothesis is that attention improves perception by selectively communicating relevant visual information. This idea has been tested primarily by measuring interactions between neurons on very short timescales, which are mathematically nearly independent of neuronal interactions on longer timescales. We tested the hypothesis that attention changes the way visual information is communicated between cortical areas on longer timescales by recording simultaneously from neurons in primary visual cortex (V1) and the middle temporal area (MT) in rhesus monkeys. We used two independent and complementary approaches. Our correlative experiment showed that attention increases the trial-to-trial response variability that is shared between the two areas. In our causal experiment, we electrically microstimulated V1 and found that attention increased the effect of stimulation on MT responses. Together, our results suggest that attention affects both the way visual stimuli are encoded within a cortical area and the extent to which visual information is communicated between areas on behaviorally relevant timescales. SIGNIFICANCE STATEMENT Visual attention dramatically improves the perception of attended stimuli. Attention has long been thought to act by selecting relevant visual information for further processing. It has been hypothesized that this selection is accomplished by increasing communication between neurons that encode attended information in different cortical areas. We recorded simultaneously

  8. Attention Increases Spike Count Correlations between Visual Cortical Areas.

    Science.gov (United States)

    Ruff, Douglas A; Cohen, Marlene R

    2016-07-13

    Visual attention, which improves perception of attended locations or objects, has long been known to affect many aspects of the responses of neuronal populations in visual cortex. There are two nonmutually exclusive hypotheses concerning the neuronal mechanisms that underlie these perceptual improvements. The first hypothesis, that attention improves the information encoded by a population of neurons in a particular cortical area, has considerable physiological support. The second hypothesis is that attention improves perception by selectively communicating relevant visual information. This idea has been tested primarily by measuring interactions between neurons on very short timescales, which are mathematically nearly independent of neuronal interactions on longer timescales. We tested the hypothesis that attention changes the way visual information is communicated between cortical areas on longer timescales by recording simultaneously from neurons in primary visual cortex (V1) and the middle temporal area (MT) in rhesus monkeys. We used two independent and complementary approaches. Our correlative experiment showed that attention increases the trial-to-trial response variability that is shared between the two areas. In our causal experiment, we electrically microstimulated V1 and found that attention increased the effect of stimulation on MT responses. Together, our results suggest that attention affects both the way visual stimuli are encoded within a cortical area and the extent to which visual information is communicated between areas on behaviorally relevant timescales. Visual attention dramatically improves the perception of attended stimuli. Attention has long been thought to act by selecting relevant visual information for further processing. It has been hypothesized that this selection is accomplished by increasing communication between neurons that encode attended information in different cortical areas. We recorded simultaneously from neurons in primary

  9. Wakefulness delta waves increase after cortical plasticity induction.

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    Assenza, G; Pellegrino, G; Tombini, M; Di Pino, G; Di Lazzaro, V

    2015-06-01

    Delta waves (DW) are present both during sleep and in wakefulness. In the first case, DW are considered effectors of synaptic plasticity, while in wakefulness, when they appear in the case of brain lesions, their functional meaning is not unanimously recognized. To throw light on the latter, we aimed to investigate the impact on DW exerted by the cortical plasticity-inducing protocol of intermittent theta burst stimulation (iTBS). Twenty healthy subjects underwent iTBS (11 real iTBS and nine sham iTBS) on the left primary motor cortex with the aim of inducing long-term potentiation (LTP)-like phenomena. Five-minute resting open-eye 32-channel EEG, right opponens pollicis motor-evoked potentials (MEPs), and alertness behavioral scales were collected before and up to 30 min after the iTBS. Power spectral density (PSD), interhemispheric coherence between homologous sensorimotor regions, and intrahemispheric coherence were calculated for the frequency bands ranging from delta to beta. Real iTBS induced a significant increase of both MEP amplitude and DW PSD lasting up to 30 min after stimulation, while sham iTBS did not. The DW increase was evident over frontal areas ipsilateral and close to the stimulated cortex (electrode F3). Neither real nor sham iTBS induced significant modifications in the PSD of theta, alpha, and beta bands and in the interhemispheric coherence. Behavioral visuo-analogic scales score did not demonstrate changes in alertness after stimulations. No correlations were found between MEP amplitude and PSD changes in the delta band. Our data showed that LTP induction in the motor cortex during wakefulness, by means of iTBS, is accompanied by a large and enduring increase of DW over the ipsilateral frontal cortex. The present results are strongly in favor of a prominent role of DW in the neural plasticity processes taking place during the awake state. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland

  10. Increased phencyclidine-induced hyperactivity following cortical cholinergic denervation.

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    Mattsson, Anna; Lindqvist, Eva; Ogren, Sven Ove; Olson, Lars

    2005-11-07

    Altered cholinergic function is considered as a potential contributing factor in the pathogenesis of schizophrenia. We hypothesize that cortical cholinergic denervation may result in changes in glutamatergic activity. Therefore, we lesioned the cholinergic corticopetal projections by local infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of rats. Possible effects of this lesion on glutamatergic systems were examined by phencyclidine-induced locomotor activity, and also by N-methyl-D-aspartate receptor binding. We find that cholinergic lesioning of neocortex leads to enhanced sensitivity to phencyclidine in the form of a dramatic increase in horizontal activity. Further, N-methyl-D-aspartate receptor binding is unaffected in denervated rats. These results suggest that aberrations in cholinergic function might lead to glutamatergic dysfunctions, which might be of relevance for the pathophysiology for schizophrenia.

  11. Increased resistance during jump exercise does not enhance cortical bone formation.

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    Boudreaux, Ramon D; Swift, Joshua M; Gasier, Heath G; Wiggs, Michael P; Hogan, Harry A; Fluckey, James D; Bloomfield, Susan A

    2014-01-01

    This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cortical bone of the tibia and femur mid-diaphyses. Sprague-Dawley rats (male, 6 months old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15), or cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE for 5 wk. Load in the HRE group was progressively increased from 80 g added to a weighted vest (50 repetitions) to 410 g (16 repetitions). The LRE rats completed the same protocol as the HRE group (same number of repetitions), with only a 30-g vest applied. Low- and high-load jump RE resulted in 6%-11% higher cortical bone mineral content and cortical bone area compared with controls, as determined by in vivo peripheral quantitative computed tomography measurements. In the femur, however, only LRE demonstrated improvements in cortical volumetric bone mineral density (+11%) and cross-sectional moment of inertia (+20%) versus the CC group. The three-point bending to failure revealed a marked increase in tibial maximum force (25%-29%), stiffness (19%-22%), and energy to maximum force (35%-55%) and a reduction in elastic modulus (-11% to 14%) in both LRE and HRE compared with controls. Dynamic histomorphometry assessed at the tibia mid-diaphysis determined that both LRE and HRE resulted in 20%-30% higher periosteal mineralizing surface versus the CC group. Mineral apposition rate and bone formation rate were significantly greater in animals in the LRE group (27%, 39%) than those in the HRE group. These data demonstrate that jump training with minimal loading is equally, and sometimes more, effective at augmenting cortical bone integrity compared with overload training in skeletally mature rats.

  12. Exercising self-control increases relative left frontal cortical activation.

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    Schmeichel, Brandon J; Crowell, Adrienne; Harmon-Jones, Eddie

    2016-02-01

    Self-control refers to the capacity to override or alter a predominant response tendency. The current experiment tested the hypothesis that exercising self-control temporarily increases approach motivation, as revealed by patterns of electrical activity in the prefrontal cortex. Participants completed a writing task that did vs did not require them to exercise self-control. Then they viewed pictures known to evoke positive, negative or neutral affect. We assessed electroencephalographic (EEG) activity while participants viewed the pictures, and participants reported their trait levels of behavioral inhibition system (BIS) and behavioral activation system (BAS) sensitivity at the end of the study. We found that exercising (vs not exercising) self-control increased relative left frontal cortical activity during picture viewing, particularly among individuals with relatively higher BAS than BIS, and particularly during positive picture viewing. A similar but weaker pattern emerged during negative picture viewing. The results suggest that exercising self-control temporarily increases approach motivation, which may help to explain the aftereffects of self-control (i.e. ego depletion). © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. Alternative normalization methods demonstrate widespread cortical hypometabolism in untreated de novo Parkinson's disease

    DEFF Research Database (Denmark)

    Berti, Valentina; Polito, C; Borghammer, Per

    2012-01-01

    , recent studies suggested that conventional data normalization procedures may not always be valid, and demonstrated that alternative normalization strategies better allow detection of low magnitude changes. We hypothesized that these alternative normalization procedures would disclose more widespread...... metabolic alterations in de novo PD. METHODS: [18F]FDG PET scans of 26 untreated de novo PD patients (Hoehn & Yahr stage I-II) and 21 age-matched controls were compared using voxel-based analysis. Normalization was performed using gray matter (GM), white matter (WM) reference regions and Yakushev...... normalization. RESULTS: Compared to GM normalization, WM and Yakushev normalization procedures disclosed much larger cortical regions of relative hypometabolism in the PD group with extensive involvement of frontal and parieto-temporal-occipital cortices, and several subcortical structures. Furthermore...

  14. Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development

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    Congyu Xu

    2017-10-01

    Full Text Available Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease. To study in vivo function of PDK1 in neuron survival during cortical development, we generate forebrain-specific PDK1 conditional knockout (cKO mice. We demonstrate that PDK1 cKO mice display striking neuron loss and increased apoptosis. We report that PDK1 cKO mice exhibit deficits on several behavioral tasks. Moreover, PDK1 cKO mice show decreased activities for Akt and mTOR. These results highlight an essential role of endogenous PDK1 in the maintenance of neuronal survival during cortical development.

  15. Evidence for increased glutamatergic cortical facilitation in children and adolescents with major depressive disorder.

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    Croarkin, Paul E; Nakonezny, Paul A; Husain, Mustafa M; Melton, Tabatha; Buyukdura, Jeylan S; Kennard, Betsy D; Emslie, Graham J; Kozel, F Andrew; Daskalakis, Zafiris J

    2013-03-01

    Converging lines of evidence implicate the glutamate and γ-aminobutyric acid neurotransmitter systems in the pathophysiology of major depressive disorder. Transcranial magnetic stimulation cortical excitability and inhibition paradigms have been used to assess cortical glutamatergic and γ-aminobutyric acid-mediated tone in adults with major depressive disorder, but not in children and adolescents. To compare measures of cortical excitability and inhibition with 4 different paradigms in a group of children and adolescents with major depressive disorder vs healthy controls. Cross-sectional study examining medication-free children and adolescents (aged 9-17 years) with major depressive disorder compared with healthy controls. Cortical excitability was assessed with motor threshold and intracortical facilitation measures. Cortical inhibition was measured with cortical silent period and intracortical inhibition paradigms. University-based child and adolescent psychiatry clinic and neurostimulation laboratory. Twenty-four participants with major depressive disorder and 22 healthy controls matched for age and sex. Patients with major depressive disorder were medication naive and had moderate to severe symptoms based on an evaluation with a child and adolescent psychiatrist and scores on the Children's Depression Rating Scale-Revised. Motor threshold, intracortical facilitation, cortical silent period, and intracortical inhibition. Compared with healthy controls, depressed patients had significantly increased intracortical facilitation at interstimulus intervals of 10 and 15 milliseconds bilaterally. There were no significant group differences in cortical inhibition measures. These findings suggest that major depressive disorder in children and adolescents is associated with increased intracortical facilitation and excessive glutamatergic activity.

  16. Cortical ensemble activity increasingly predicts behaviour outcomes during learning of a motor task

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    Laubach, Mark; Wessberg, Johan; Nicolelis, Miguel A. L.

    2000-06-01

    When an animal learns to make movements in response to different stimuli, changes in activity in the motor cortex seem to accompany and underlie this learning. The precise nature of modifications in cortical motor areas during the initial stages of motor learning, however, is largely unknown. Here we address this issue by chronically recording from neuronal ensembles located in the rat motor cortex, throughout the period required for rats to learn a reaction-time task. Motor learning was demonstrated by a decrease in the variance of the rats' reaction times and an increase in the time the animals were able to wait for a trigger stimulus. These behavioural changes were correlated with a significant increase in our ability to predict the correct or incorrect outcome of single trials based on three measures of neuronal ensemble activity: average firing rate, temporal patterns of firing, and correlated firing. This increase in prediction indicates that an association between sensory cues and movement emerged in the motor cortex as the task was learned. Such modifications in cortical ensemble activity may be critical for the initial learning of motor tasks.

  17. Traumatic Brain Injury Increases Cortical Glutamate Network Activity by Compromising GABAergic Control.

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    Cantu, David; Walker, Kendall; Andresen, Lauren; Taylor-Weiner, Amaro; Hampton, David; Tesco, Giuseppina; Dulla, Chris G

    2015-08-01

    Traumatic brain injury (TBI) is a major risk factor for developing pharmaco-resistant epilepsy. Although disruptions in brain circuitry are associated with TBI, the precise mechanisms by which brain injury leads to epileptiform network activity is unknown. Using controlled cortical impact (CCI) as a model of TBI, we examined how cortical excitability and glutamatergic signaling was altered following injury. We optically mapped cortical glutamate signaling using FRET-based glutamate biosensors, while simultaneously recording cortical field potentials in acute brain slices 2-4 weeks following CCI. Cortical electrical stimulation evoked polyphasic, epileptiform field potentials and disrupted the input-output relationship in deep layers of CCI-injured cortex. High-speed glutamate biosensor imaging showed that glutamate signaling was significantly increased in the injured cortex. Elevated glutamate responses correlated with epileptiform activity, were highest directly adjacent to the injury, and spread via deep cortical layers. Immunoreactivity for markers of GABAergic interneurons were significantly decreased throughout CCI cortex. Lastly, spontaneous inhibitory postsynaptic current frequency decreased and spontaneous excitatory postsynaptic current increased after CCI injury. Our results suggest that specific cortical neuronal microcircuits may initiate and facilitate the spread of epileptiform activity following TBI. Increased glutamatergic signaling due to loss of GABAergic control may provide a mechanism by which TBI can give rise to post-traumatic epilepsy. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Increased Cortical Thickness in Male-to-Female Transsexualism.

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    Luders, Eileen; Sánchez, Francisco J; Tosun, Duygu; Shattuck, David W; Gaser, Christian; Vilain, Eric; Toga, Arthur W

    2012-08-01

    The degree to which one identifies as male or female has a profound impact on one's life. Yet, there is a limited understanding of what contributes to this important characteristic termed gender identity . In order to reveal factors influencing gender identity, studies have focused on people who report strong feelings of being the opposite sex, such as male-to-female (MTF) transsexuals. To investigate potential neuroanatomical variations associated with transsexualism, we compared the regional thickness of the cerebral cortex between 24 MTF transsexuals who had not yet been treated with cross-sex hormones and 24 age-matched control males. Results revealed thicker cortices in MTF transsexuals, both within regions of the left hemisphere (i.e., frontal and orbito-frontal cortex, central sulcus, perisylvian regions, paracentral gyrus) and right hemisphere (i.e., pre-/post-central gyrus, parietal cortex, temporal cortex, precuneus, fusiform, lingual, and orbito-frontal gyrus). These findings provide further evidence that brain anatomy is associated with gender identity, where measures in MTF transsexuals appear to be shifted away from gender-congruent men.

  19. Combining diffusion magnetic resonance tractography with stereology highlights increased cross-cortical integration in primates.

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    Charvet, Christine J; Hof, Patrick R; Raghanti, Mary Ann; Van Der Kouwe, Andre J; Sherwood, Chet C; Takahashi, Emi

    2017-04-01

    The isocortex of primates is disproportionately expanded relative to many other mammals, yet little is known about what the expansion of the isocortex entails for differences in cellular composition and connectivity patterns in primates. Across the depth of the isocortex, neurons exhibit stereotypical patterns of projections. Upper-layer neurons (i.e., layers II-IV) project within and across cortical areas, whereas many lower-layer pyramidal neurons (i.e., layers V-VI) favor connections to subcortical regions. To identify evolutionary changes in connectivity patterns, we quantified upper (i.e., layers II-IV)- and lower (i.e., layers V-VI)-layer neuron numbers in primates and other mammals such as rodents and carnivores. We also used MR tractography based on high-angular resolution diffusion imaging and diffusion spectrum imaging to compare anterior-to-posterior corticocortical tracts between primates and other mammals. We found that primates possess disproportionately more upper-layer neurons as well as an expansion of anterior-to-posterior corticocortical tracts compared with other mammals. Taken together, these findings demonstrate that primates deviate from other mammals in exhibiting increased cross-cortical connectivity. J. Comp. Neurol. 525:1075-1093, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Increased susceptibility to cortical spreading depression in the mouse model of familial hemiplegic migraine type 2.

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    Loredana Leo

    2011-06-01

    Full Text Available Familial hemiplegic migraine type 2 (FHM2 is an autosomal dominant form of migraine with aura that is caused by mutations of the α2-subunit of the Na,K-ATPase, an isoform almost exclusively expressed in astrocytes in the adult brain. We generated the first FHM2 knock-in mouse model carrying the human W887R mutation in the Atp1a2 orthologous gene. Homozygous Atp1a2(R887/R887 mutants died just after birth, while heterozygous Atp1a2(+/R887 mice showed no apparent clinical phenotype. The mutant α2 Na,K-ATPase protein was barely detectable in the brain of homozygous mutants and strongly reduced in the brain of heterozygous mutants, likely as a consequence of endoplasmic reticulum retention and subsequent proteasomal degradation, as we demonstrate in transfected cells. In vivo analysis of cortical spreading depression (CSD, the phenomenon underlying migraine aura, revealed a decreased induction threshold and an increased velocity of propagation in the heterozygous FHM2 mouse. Since several lines of evidence involve a specific role of the glial α2 Na,K pump in active reuptake of glutamate from the synaptic cleft, we hypothesize that CSD facilitation in the FHM2 mouse model is sustained by inefficient glutamate clearance by astrocytes and consequent increased cortical excitatory neurotransmission. The demonstration that FHM2 and FHM1 mutations share the ability to facilitate induction and propagation of CSD in mouse models further support the role of CSD as a key migraine trigger.

  1. Preliminary findings demonstrating latent effects of early adolescent marijuana use onset on cortical architecture

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    Francesca M. Filbey

    2015-12-01

    Conclusions: Divergent patterns between current MJ use and elements of cortical architecture were associated with early MJ use onset. Considering brain development in early adolescence, findings are consistent with disruptions in pruning. However, divergence with continued use for many years thereafter suggests altered trajectories of brain maturation during late adolescence and beyond.

  2. Bisensory stimulation increases gamma-responses over multiple cortical regions.

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    Sakowitz, O W; Quiroga, R Q; Schürmann, M; Başar, E

    2001-04-01

    In the framework of the discussion about gamma (approx. 40 Hz) oscillations as information carriers in the brain, we investigated the relationship between gamma responses in the EEG and intersensory association. Auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) were compared with bisensory evoked potentials (BEPs; simultaneous auditory and visual stimulation) in 15 subjects. Gamma responses in AEPs, VEPs and BEPs were assessed by means of wavelet decomposition. Overall maximum gamma-components post-stimulus were highest in BEPs (P < 0.01). Bisensory evoked gamma-responses also showed significant central, parietal and occipital amplitude-increases (P < 0.001, P < 0.01, P < 0.05, respectively; prestimulus interval as baseline). These were of greater magnitude when compared with the unisensory responses. As a correlate of the marked gamma responses to bimodal stimulation we suggest a process of 'intersensory association', i.e. one of the steps between sensory transmission and perception. Our data may be interpreted as a further example of function-related gamma responses in the EEG.

  3. Cortical activation in profoundly deaf patients during cochlear implant stimulation demonstrated by H2(15)O PET

    International Nuclear Information System (INIS)

    Herzog, H.; Lamprecht, A.; Kuehn, A.R.; Roden, W.; Vosteen, K.H.; Feinendegen, L.E.

    1991-01-01

    Cochlear implants (CIs) are used to provide sensations of sound to profoundly deaf patients. The performance of the CI is assessed mainly by the subjective reports of patients. The aim of this study was to look for objective cortical responses to the stimulation of the CI. Two postlingually and two prelingually deaf patients were investigated by positron emission tomography (PET) using 15 O-labeled water (H 2 15 O) to determine the regional cerebral blood flow (rCBF). Instead of quantifying rCBF in absolute terms, it was estimated by referring the regional tissue concentration of H 2 15 O to the mean whole brain concentration. CI stimulation encoded from white noise and sequential words led to an increased rCBF in the primary and secondary (Wernicke) auditory cortex. Relative elevations of up to 33% were observed bilaterally, although they were higher contralateral to the CI. These results were obtained not only in the postlingually deaf patients but also in two patients who had never been able to hear. Thus, it could be demonstrated that PET measurements of cerebral H 2 15 O distribution yield objective responses of the central auditory system during electrical stimulation by CIs in profoundly deaf patients

  4. MRI demonstration of cortical laminar necrosis and delayed white matter injury in anoxic encephalopathy

    International Nuclear Information System (INIS)

    Sawada, H.; Udaka, F.; Seriu, N.; Shindou, K.; Kameyama, M.; Tsujimura, M.

    1990-01-01

    We performed serial radiological examinations on a patient with anoxic encephalopathy. In the early term after the anoxic insult, T1-weighted MRI revealed high signal intensity area distributed laminarly in the cerebral cortex and diffusely in the putamen, which were thought to refect the cortical necrosis and necrosis in the putamen. Single photon emission computed tomography using I-123 isopropylamphetamine showed persistent hypoperfusion in the arterial watershed zones. T2-weighted MRI performed several months after the anoxic episode revealed diffuse high-intensity lesions in the arterial watershed zones. These delayed-onset white matter lesions continued to extend over several months. (orig.)

  5. Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin-1.

    Science.gov (United States)

    Radonjić, Nevena V; Jakovcevski, Igor; Bumbaširević, Vladimir; Petronijević, Nataša D

    2013-06-01

    Perinatal phencyclidine (PCP) administration in rat blocks the N-methyl D-aspartate receptor (NMDAR) and causes symptoms reminiscent of schizophrenia in human. A growing body of evidence suggests that alterations in γ-aminobutyric acid (GABA) interneuron neurotransmission may be associated with schizophrenia. Neuregulin-1 (NRG-1) is a trophic factor important for neurodevelopment, synaptic plasticity, and wiring of GABA circuits. The aim of this study was to determine the long-term effects of perinatal PCP administration on the projection and local circuit neurons and NRG-1 expression in the cortex and hippocampus. Rats were treated on postnatal day 2 (P2), P6, P9, and P12 with either PCP (10 mg/kg) or saline. Morphological studies and determination of NRG-1 expression were performed at P70. We demonstrate reduced densities of principal neurons in the CA3 and dentate gyrus (DG) subregions of the hippocampus and a reduction of major interneuronal populations in all cortical and hippocampal regions studied in PCP-treated rats compared with controls. For the first time, we show the reduced density of reelin- and somatostatin-positive cells in the cortex and hippocampus of animals perinatally treated with PCP. Furthermore, an increase in the numbers of perisomatic inhibitory terminals around the principal cells was observed in the motor cortex and DG. We also show that perinatal PCP administration leads to an increased NRG-1 expression in the cortex and hippocampus. Taken together, our findings demonstrate that perinatal PCP administration increases NRG-1 expression and reduces the number of projecting and local circuit neurons, revealing complex consequences of NMDAR blockade.

  6. Aging increases microglial proliferation, delays cell migration, and decreases cortical neurogenesis after focal cerebral ischemia.

    Science.gov (United States)

    Moraga, Ana; Pradillo, Jesús M; García-Culebras, Alicia; Palma-Tortosa, Sara; Ballesteros, Ivan; Hernández-Jiménez, Macarena; Moro, María A; Lizasoain, Ignacio

    2015-05-10

    Aging is not just a risk factor of stroke, but it has also been associated with poor recovery. It is known that stroke-induced neurogenesis is reduced but maintained in the aged brain. However, there is no consensus on how neurogenesis is affected after stroke in aged animals. Our objective is to determine the role of aging on the process of neurogenesis after stroke. We have studied neurogenesis by analyzing proliferation, migration, and formation of new neurons, as well as inflammatory parameters, in a model of cerebral ischemia induced by permanent occlusion of the middle cerebral artery in young- (2 to 3 months) and middle-aged mice (13 to 14 months). Aging increased both microglial proliferation, as shown by a higher number of BrdU(+) cells and BrdU/Iba1(+) cells in the ischemic boundary and neutrophil infiltration. Interestingly, aging increased the number of M1 monocytes and N1 neutrophils, consistent with pro-inflammatory phenotypes when compared with the alternative M2 and N2 phenotypes. Aging also inhibited (subventricular zone) SVZ cell proliferation by decreasing both the number of astrocyte-like type-B (prominin-1(+)/epidermal growth factor receptor (EGFR)(+)/nestin(+)/glial fibrillary acidic protein (GFAP)(+) cells) and type-C cells (prominin-1(+)/EGFR(+)/nestin(-)/Mash1(+) cells), and not affecting apoptosis, 1 day after stroke. Aging also inhibited migration of neuroblasts (DCX(+) cells), as indicated by an accumulation of neuroblasts at migratory zones 14 days after injury; consistently, aged mice presented a smaller number of differentiated interneurons (NeuN(+)/BrdU(+) and GAD67(+) cells) in the peri-infarct cortical area 14 days after stroke. Our data confirm that stroke-induced neurogenesis is maintained but reduced in aged animals. Importantly, we now demonstrate that aging not only inhibits proliferation of specific SVZ cell subtypes but also blocks migration of neuroblasts to the damaged area and decreases the number of new interneurons in

  7. mGluR5 ablation in cortical glutamatergic neurons increases novelty-induced locomotion.

    Directory of Open Access Journals (Sweden)

    Chris P Jew

    Full Text Available The group I metabotropic glutamate receptor 5 (mGluR5 has been implicated in the pathology of various neurological disorders including schizophrenia, ADHD, and autism. mGluR5-dependent synaptic plasticity has been described at a variety of neural connections and its signaling has been implicated in several behaviors. These behaviors include locomotor reactivity to novel environment, sensorimotor gating, anxiety, and cognition. mGluR5 is expressed in glutamatergic neurons, inhibitory neurons, and glia in various brain regions. In this study, we show that deleting mGluR5 expression only in principal cortical neurons leads to defective cannabinoid receptor 1 (CB1R dependent synaptic plasticity in the prefrontal cortex. These cortical glutamatergic mGluR5 knockout mice exhibit increased novelty-induced locomotion, and their locomotion can be further enhanced by treatment with the psychostimulant methylphenidate. Despite a modest reduction in repetitive behaviors, cortical glutamatergic mGluR5 knockout mice are normal in sensorimotor gating, anxiety, motor balance/learning and fear conditioning behaviors. These results show that mGluR5 signaling in cortical glutamatergic neurons is required for precisely modulating locomotor reactivity to a novel environment but not for sensorimotor gating, anxiety, motor coordination, several forms of learning or social interactions.

  8. Increased Executive Functioning, Attention, and Cortical Thickness in White-Collar Criminals

    Science.gov (United States)

    Raine, Adrian; Laufer, William S.; Yang, Yaling; Narr, Katherine L.; Thompson, Paul; Toga, Arthur W.

    2011-01-01

    Very little is known on white collar crime and how it differs to other forms of offending. This study tests the hypothesis that white collar criminals have better executive functioning, enhanced information processing, and structural brain superiorities compared to offender controls. Using a case-control design, executive functioning, orienting, and cortical thickness was assessed in 21 white collar criminals matched with 21 controls on age, gender, ethnicity, and general level of criminal offending. White collar criminals had significantly better executive functioning, increased electrodermal orienting, increased arousal, and increased cortical gray matter thickness in the ventromedial prefrontal cortex, inferior frontal gyrus, somatosensory cortex, and the temporal-parietal junction compared to controls. Results, while initial, constitute the first findings on neurobiological characteristics of white-collar criminals It is hypothesized that white collar criminals have information-processing and brain superiorities that give them an advantage in perpetrating criminal offenses in occupational settings. PMID:22002326

  9. Children with dyslexia show cortical hyperactivation in response to increasing literacy processing demands

    Directory of Open Access Journals (Sweden)

    Frøydis eMorken

    2014-12-01

    Full Text Available This fMRI study aimed to examine how differences in literacy processing demands may affect cortical activation patterns in 11- to 12-year-old children with dyslexia as compared to children with typical reading skills. 11 children with and 18 without dyslexia were assessed using a reading paradigm based on different stages of literacy development. In the analyses, six regions showed an interaction effect between group and condition in a factorial ANOVA. These regions were selected as regions of interest for further analyses. Overall, the dyslexia group showed cortical hyperactivation compared to the typical group. The difference between the groups tended to increase with increasing processing demands. Differences in cortical activation were not reflected in in-scanner reading performance. The six regions further grouped into three patterns, which are discussed in terms of processing demands, compensatory mechanisms, orthography and contextual facilitation. We conclude that the observed hyperactivation is chiefly a result of compensatory activity, modulated by other factors.

  10. Binaural beats increase interhemispheric alpha-band coherence between auditory cortices.

    Science.gov (United States)

    Solcà, Marco; Mottaz, Anaïs; Guggisberg, Adrian G

    2016-02-01

    Binaural beats (BBs) are an auditory illusion occurring when two tones of slightly different frequency are presented separately to each ear. BBs have been suggested to alter physiological and cognitive processes through synchronization of the brain hemispheres. To test this, we recorded electroencephalograms (EEG) at rest and while participants listened to BBs or a monaural control condition during which both tones were presented to both ears. We calculated for each condition the interhemispheric coherence, which expressed the synchrony between neural oscillations of both hemispheres. Compared to monaural beats and resting state, BBs enhanced interhemispheric coherence between the auditory cortices. Beat frequencies in the alpha (10 Hz) and theta (4 Hz) frequency range both increased interhemispheric coherence selectively at alpha frequencies. In a second experiment, we evaluated whether this coherence increase has a behavioral aftereffect on binaural listening. No effects were observed in a dichotic digit task performed immediately after BBs presentation. Our results suggest that BBs enhance alpha-band oscillation synchrony between the auditory cortices during auditory stimulation. This effect seems to reflect binaural integration rather than entrainment. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Envelope enhancement increases cortical sensitivity to interaural envelope delays with acoustic and electric hearing.

    Directory of Open Access Journals (Sweden)

    Douglas E H Hartley

    Full Text Available Evidence from human psychophysical and animal electrophysiological studies suggests that sensitivity to interaural time delay (ITD in the modulating envelope of a high-frequency carrier can be enhanced using half-wave rectified stimuli. Recent evidence has shown potential benefits of equivalent electrical stimuli to deaf individuals with bilateral cochlear implants (CIs. In the current study we assessed the effects of envelope shape on ITD sensitivity in the primary auditory cortex of normal-hearing ferrets, and profoundly-deaf animals with bilateral CIs. In normal-hearing animals, cortical sensitivity to ITDs (±1 ms in 0.1-ms steps was assessed in response to dichotically-presented i sinusoidal amplitude-modulated (SAM and ii half-wave rectified (HWR tones (100-ms duration; 70 dB SPL presented at the best-frequency of the unit over a range of modulation frequencies. In separate experiments, adult ferrets were deafened with neomycin administration and bilaterally-implanted with intra-cochlear electrode arrays. Electrically-evoked auditory brainstem responses (EABRs were recorded in response to bipolar electrical stimulation of the apical pair of electrodes with singe biphasic current pulses (40 µs per phase over a range of current levels to measure hearing thresholds. Subsequently, we recorded cortical sensitivity to ITDs (±800 µs in 80-µs steps within the envelope of SAM and HWR biphasic-pulse trains (40 µs per phase; 6000 pulses per second, 100-ms duration over a range of modulation frequencies. In normal-hearing animals, nearly a third of cortical neurons were sensitive to envelope-ITDs in response to SAM tones. In deaf animals with bilateral CI, the proportion of ITD-sensitive cortical neurons was approximately a fifth in response to SAM pulse trains. In normal-hearing and deaf animals with bilateral CI the proportion of ITD sensitive units and neural sensitivity to ITDs increased in response to HWR, compared with SAM stimuli

  12. Increased cortical-limbic anatomical network connectivity in major depression revealed by diffusion tensor imaging.

    Directory of Open Access Journals (Sweden)

    Peng Fang

    Full Text Available Magnetic resonance imaging studies have reported significant functional and structural differences between depressed patients and controls. Little attention has been given, however, to the abnormalities in anatomical connectivity in depressed patients. In the present study, we aim to investigate the alterations in connectivity of whole-brain anatomical networks in those suffering from major depression by using machine learning approaches. Brain anatomical networks were extracted from diffusion magnetic resonance images obtained from both 22 first-episode, treatment-naive adults with major depressive disorder and 26 matched healthy controls. Using machine learning approaches, we differentiated depressed patients from healthy controls based on their whole-brain anatomical connectivity patterns and identified the most discriminating features that represent between-group differences. Classification results showed that 91.7% (patients=86.4%, controls=96.2%; permutation test, p<0.0001 of subjects were correctly classified via leave-one-out cross-validation. Moreover, the strengths of all the most discriminating connections were increased in depressed patients relative to the controls, and these connections were primarily located within the cortical-limbic network, especially the frontal-limbic network. These results not only provide initial steps toward the development of neurobiological diagnostic markers for major depressive disorder, but also suggest that abnormal cortical-limbic anatomical networks may contribute to the anatomical basis of emotional dysregulation and cognitive impairments associated with this disease.

  13. Modulation of Specific Sensory Cortical Areas by Segregated Basal Forebrain Cholinergic Neurons Demonstrated by Neuronal Tracing and Optogenetic Stimulation in Mice.

    Science.gov (United States)

    Chaves-Coira, Irene; Barros-Zulaica, Natali; Rodrigo-Angulo, Margarita; Núñez, Ángel

    2016-01-01

    Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated

  14. Huperzine A prophylaxis against pentylenetetrazole-induced seizures in rats is associated with increased cortical inhibition.

    Science.gov (United States)

    Gersner, R; Ekstein, D; Dhamne, S C; Schachter, S C; Rotenberg, A

    2015-11-01

    Huperzine A (HupA) is a naturally occurring compound found in the firmoss Huperzia serrata. While HupA is a potent acetylcholinesterase inhibitor, its full pharmacologic profile is incompletely described. Since previous works suggested a capacity for HupA to prophylax against seizures, we tested the HupA antiepileptic potential in pentylenetetrazole (PTZ) rat epilepsy model and explored its mechanism of action by spectral EEG analysis and by paired-pulse transcranial magnetic stimulation (ppTMS), a measure of GABA-mediated intracortical inhibition. We tested whether HupA suppresses seizures in the rat PTZ acute seizure model, and quantified latency to first myoclonus and to generalized tonic-clonic seizure, and spike frequency on EEG. Additionally, we measured power in the EEG gamma frequency band which is associated with GABAergic cortical interneuron activation. Then, as a step toward further examining the HupA antiepileptic mechanism of action, we tested long-interval intracortical inhibition (LICI) using ppTMS coupled with electromyography to assess whether HupA augments GABA-mediated paired-pulse inhibition of the motor evoked potential. We also tested whether the HupA effect on paired-pulse inhibition was central or peripheral by comparison of outcomes following administration of HupA or the peripheral acetylcholinesterase inhibitor pyridostigmine. We also tested whether the HupA effect was dependent on central muscarinic or GABAA receptors by co-administration of HupA and atropine or PTZ, respectively. In tests of antiepileptic potential, HupA suppressed seizures and epileptic spikes on EEG. Spectral EEG analysis also revealed enhanced gamma frequency band power with HupA treatment. By ppTMS we found that HupA increases intracortical inhibition and blocks PTZ-induced cortical excitation. Atropine co-administration with HupA did not alter HupA-induced intracortical inhibition suggesting independent of muscarinic acetylcholine receptors mechanism in this model

  15. TMS-induced cortical potentiation during wakefulness locally increases slow wave activity during sleep.

    Directory of Open Access Journals (Sweden)

    Reto Huber

    2007-03-01

    Full Text Available Sleep slow wave activity (SWA is thought to reflect sleep need, increasing in proportion to the length of prior wakefulness and decreasing during sleep. However, the process responsible for SWA regulation is not known. We showed recently that SWA increases locally after a learning task involving a circumscribed brain region, suggesting that SWA may reflect plastic changes triggered by learning.To test this hypothesis directly, we used transcranial magnetic stimulation (TMS in conjunction with high-density EEG in humans. We show that 5-Hz TMS applied to motor cortex induces a localized potentiation of TMS-evoked cortical EEG responses. We then show that, in the sleep episode following 5-Hz TMS, SWA increases markedly (+39.1+/-17.4%, p<0.01, n = 10. Electrode coregistration with magnetic resonance images localized the increase in SWA to the same premotor site as the maximum TMS-induced potentiation during wakefulness. Moreover, the magnitude of potentiation during wakefulness predicts the local increase in SWA during sleep.These results provide direct evidence for a link between plastic changes and the local regulation of sleep need.

  16. Experimental demonstration of superconducting critical temperature increase in electromagnetic metamaterials.

    Science.gov (United States)

    Smolyaninova, Vera N; Yost, Bradley; Zander, Kathryn; Osofsky, M S; Kim, Heungsoo; Saha, Shanta; Greene, R L; Smolyaninov, Igor I

    2014-12-04

    A recent proposal that the metamaterial approach to dielectric response engineering may increase the critical temperature of a composite superconductor-dielectric metamaterial has been tested in experiments with compressed mixtures of tin and barium titanate nanoparticles of varying composition. An increase of the critical temperature of the order of ΔT ~ 0.15 K compared to bulk tin has been observed for 40% volume fraction of barium titanate nanoparticles. Similar results were also obtained with compressed mixtures of tin and strontium titanate nanoparticles.

  17. Experimental demonstration of superconducting critical temperature increase in electromagnetic metamaterials

    Science.gov (United States)

    Smolyaninova, Vera N.; Yost, Bradley; Zander, Kathryn; Osofsky, M. S.; Kim, Heungsoo; Saha, Shanta; Greene, R. L.; Smolyaninov, Igor I.

    2014-12-01

    A recent proposal that the metamaterial approach to dielectric response engineering may increase the critical temperature of a composite superconductor-dielectric metamaterial has been tested in experiments with compressed mixtures of tin and barium titanate nanoparticles of varying composition. An increase of the critical temperature of the order of ΔT ~ 0.15 K compared to bulk tin has been observed for 40% volume fraction of barium titanate nanoparticles. Similar results were also obtained with compressed mixtures of tin and strontium titanate nanoparticles.

  18. Increase in cortical pyramidal cell excitability accompanies depression-like behavior in mice: a transcranial magnetic stimulation study.

    Science.gov (United States)

    Sun, Peng; Wang, Furong; Wang, Li; Zhang, Yu; Yamamoto, Ryo; Sugai, Tokio; Zhang, Qing; Wang, Zhengda; Kato, Nobuo

    2011-11-09

    Clinical evidence suggests that cortical excitability is increased in depressives. We investigated its cellular basis in a mouse model of depression. In a modified version of forced swimming (FS), mice were initially forced to swim for 5 consecutive days and then were treated daily with repetitive transcranial magnetic stimulation (rTMS) or sham treatment for the following 4 weeks without swimming. On day 2 through day 5, the mice manifested depression-like behaviors. The next and last FS was performed 4 weeks later, which revealed a 4 week maintenance of depression-like behavior in the sham mice. In slices from the sham controls, excitability in cingulate cortex pyramidal cells was elevated in terms of membrane potential and frequencies of spikes evoked by current injection. Depolarized resting potential was shown to depend on suppression of large conductance calcium-activated potassium (BK) channels. This BK channel suppression was confirmed by measuring spike width, which depends on BK channels. Chronic rTMS treatment during the 4 week period significantly reduced the depression-like behavior. In slices obtained from the rTMS mice, normal excitability and BK channel activity were recovered. Expression of a scaffold protein Homer1a was reduced by the FS and reversed by rTMS in the cingulate cortex. Similar recovery in the same behavioral, electrophysiological, and biochemical features was observed after chronic imipramine treatment. The present study demonstrated that manifestation and disappearance of depression-like behavior are in parallel with increase and decrease in cortical neuronal excitability in mice and suggested that regulation of BK channels by Homer1a is involved in this parallelism.

  19. Global ablation of the mitochondrial calcium uniporter increases glycolysis in cortical neurons subjected to energetic stressors.

    Science.gov (United States)

    Nichols, Matthew; Elustondo, Pia A; Warford, Jordan; Thirumaran, Aruloli; Pavlov, Evgeny V; Robertson, George S

    2017-08-01

    The effects of global mitochondrial calcium (Ca 2+ ) uniporter (MCU) deficiency on hypoxic-ischemic (HI) brain injury, neuronal Ca 2+ handling, bioenergetics and hypoxic preconditioning (HPC) were examined. Forebrain mitochondria isolated from global MCU nulls displayed markedly reduced Ca 2+ uptake and Ca 2+ -induced opening of the membrane permeability transition pore. Despite evidence that these effects should be neuroprotective, global MCU nulls and wild-type (WT) mice suffered comparable HI brain damage. Energetic stress enhanced glycolysis and depressed Complex I activity in global MCU null, relative to WT, cortical neurons. HI reduced forebrain NADH levels more in global MCU nulls than WT mice suggesting that increased glycolytic consumption of NADH suppressed Complex I activity. Compared to WT neurons, pyruvate dehydrogenase (PDH) was hyper-phosphorylated in MCU nulls at several sites that lower the supply of substrates for the tricarboxylic acid cycle. Elevation of cytosolic Ca 2+ with glutamate or ionomycin decreased PDH phosphorylation in MCU null neurons suggesting the use of alternative mitochondrial Ca 2+ transport. Under basal conditions, global MCU nulls showed similar increases of Ca 2+ handling genes in the hippocampus as WT mice subjected to HPC. We propose that long-term adaptations, common to HPC, in global MCU nulls compromise resistance to HI brain injury and disrupt HPC.

  20. Family nurture intervention in preterm infants increases early development of cortical activity and independence of regional power trajectories.

    Science.gov (United States)

    Welch, Martha G; Stark, Raymond I; Grieve, Philip G; Ludwig, Robert J; Isler, Joseph R; Barone, Joseph L; Myers, Michael M

    2017-12-01

    Premature delivery and maternal separation during hospitalisation increase infant neurodevelopmental risk. Previously, a randomised controlled trial of Family Nurture Intervention (FNI) in the neonatal intensive care unit demonstrated improvement across multiple mother and infant domains including increased electroencephalographic (EEG) power in the frontal polar region at term age. New aims were to quantify developmental changes in EEG power in all brain regions and frequencies and correlate developmental changes in EEG power among regions. EEG (128 electrodes) was obtained at 34-44 weeks postmenstrual age from preterm infants born 26-34 weeks. Forty-four infants were treated with Standard Care and 53 with FNI. EEG power was computed in 10 frequency bands (1-48 Hz) in 10 brain regions and in active and quiet sleep. Percent change/week in EEG power was increased in FNI in 132/200 tests (p regional independence in those developmental rates of change. This study strengthens the conclusion that FNI promotes cerebral cortical development of preterm infants. The findings indicate that developmental changes in EEG may provide biomarkers for risk in preterm infants as well as proximal markers of effects of FNI. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  1. Curved reconstructions versus three-dimensional surface rendering in the demonstration of cortical lesions in patients with extratemporal epilepsy

    NARCIS (Netherlands)

    Meiners, LC; Scheffers, JM; De Kort, GAP; Burger, H; Van Huffelen, AC; Van Rijen, PC; Van Veelen, CWM

    RATIONALE AND OBJECTIVES. TO compare the visibility and localization of extratemporal cortical lesions in extratemporal epilepsy by using curved reconstruction (CR) and three-dimensional surface rendering (3D SR) of 3D-acquired MR images and to study the degree of confidence with which localizations

  2. Cortical and sub-cortical effects in primate models of cocaine use: implications for addiction and the increased risk of psychiatric illness.

    Science.gov (United States)

    Bradberry, Charles W

    2011-02-01

    Drug abuse is a serious risk factor for the incidence and severity of multiple psychiatric illnesses. Understanding the neurobiological consequences of repeated exposure to abused drugs can help to inform how those risks are manifested in terms of specific neurochemical mechanisms and brain networks. This review examines selective studies in non-human primates that employed a cocaine self-administration model. Neurochemical consequences of chronic exposure appear to differ from observations in rodent studies. Whereas chronic intermittent exposure in the rodent is usually associated with a dose-dependent increase in dopaminergic response to a cocaine challenge, in the rhesus monkey, high cumulative exposure was not observed to cause a sensitized dopamine response. These non-human primate observations are concordant with clinical findings in human users. The results of cue exposure studies on dopaminergic transmission are also reviewed. Direct microdialysis measurements indicate that there is not a sustained increase in dopamine associated with cocaine-linked cues. As an alternative to striatal dopaminergic mechanisms mediating cue effects, single unit studies in prefrontal cortex during self-administration in monkeys suggests the orbitofrontal and anterior cingulate cortex are strongly engaged by cocaine cues. Based on the strong clinical imaging literature on cortical and cognitive dysfunction associated with addiction, it is proposed that the strong engagement of cortical systems during repeated cocaine reinforcement results in maladaptive changes that contribute to the risks of drug use for exacerbation of other psychiatric disorders.

  3. An in silico agent-based model demonstrates Reelin function in directing lamination of neurons during cortical development.

    Science.gov (United States)

    Caffrey, James R; Hughes, Barry D; Britto, Joanne M; Landman, Kerry A

    2014-01-01

    The characteristic six-layered appearance of the neocortex arises from the correct positioning of pyramidal neurons during development and alterations in this process can cause intellectual disabilities and developmental delay. Malformations in cortical development arise when neurons either fail to migrate properly from the germinal zones or fail to cease migration in the correct laminar position within the cortical plate. The Reelin signalling pathway is vital for correct neuronal positioning as loss of Reelin leads to a partially inverted cortex. The precise biological function of Reelin remains controversial and debate surrounds its role as a chemoattractant or stop signal for migrating neurons. To investigate this further we developed an in silico agent-based model of cortical layer formation. Using this model we tested four biologically plausible hypotheses for neuron motility and four biologically plausible hypotheses for the loss of neuron motility (conversion from migration). A matrix of 16 combinations of motility and conversion rules was applied against the known structure of mouse cortical layers in the wild-type cortex, the Reelin-null mutant, the Dab1-null mutant and a conditional Dab1 mutant. Using this approach, many combinations of motility and conversion mechanisms can be rejected. For example, the model does not support Reelin acting as a repelling or as a stopping signal. In contrast, the study lends very strong support to the notion that the glycoprotein Reelin acts as a chemoattractant for neurons. Furthermore, the most viable proposition for the conversion mechanism is one in which conversion is affected by a motile neuron sensing in the near vicinity neurons that have already converted. Therefore, this model helps elucidate the function of Reelin during neuronal migration and cortical development.

  4. An in silico agent-based model demonstrates Reelin function in directing lamination of neurons during cortical development.

    Directory of Open Access Journals (Sweden)

    James R Caffrey

    Full Text Available The characteristic six-layered appearance of the neocortex arises from the correct positioning of pyramidal neurons during development and alterations in this process can cause intellectual disabilities and developmental delay. Malformations in cortical development arise when neurons either fail to migrate properly from the germinal zones or fail to cease migration in the correct laminar position within the cortical plate. The Reelin signalling pathway is vital for correct neuronal positioning as loss of Reelin leads to a partially inverted cortex. The precise biological function of Reelin remains controversial and debate surrounds its role as a chemoattractant or stop signal for migrating neurons. To investigate this further we developed an in silico agent-based model of cortical layer formation. Using this model we tested four biologically plausible hypotheses for neuron motility and four biologically plausible hypotheses for the loss of neuron motility (conversion from migration. A matrix of 16 combinations of motility and conversion rules was applied against the known structure of mouse cortical layers in the wild-type cortex, the Reelin-null mutant, the Dab1-null mutant and a conditional Dab1 mutant. Using this approach, many combinations of motility and conversion mechanisms can be rejected. For example, the model does not support Reelin acting as a repelling or as a stopping signal. In contrast, the study lends very strong support to the notion that the glycoprotein Reelin acts as a chemoattractant for neurons. Furthermore, the most viable proposition for the conversion mechanism is one in which conversion is affected by a motile neuron sensing in the near vicinity neurons that have already converted. Therefore, this model helps elucidate the function of Reelin during neuronal migration and cortical development.

  5. Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study.

    Directory of Open Access Journals (Sweden)

    Makii Muthalib

    Full Text Available Neuroimaging studies have shown neuromuscular electrical stimulation (NMES-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC, premotor cortex (PMC, supplementary motor area (SMA, and secondary somatosensory area (S2, as well as regions of the prefrontal cortex (PFC known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI, and with reference to voluntary (VOL wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb and deoxygenated (HHb hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2. However, the level and area of contralateral sensorimotor network (including PFC activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

  6. Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study.

    Science.gov (United States)

    Muthalib, Makii; Re, Rebecca; Zucchelli, Lucia; Perrey, Stephane; Contini, Davide; Caffini, Matteo; Spinelli, Lorenzo; Kerr, Graham; Quaresima, Valentina; Ferrari, Marco; Torricelli, Alessandro

    2015-01-01

    Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

  7. Increase in Prefrontal Cortical Volume following Cognitive Behavioural Therapy in Patients with Chronic Fatigue Syndrome

    Science.gov (United States)

    de Lange, Floris P.; Koers, Anda; Kalkman, Joke S.; Bleijenberg, Gijs; Hagoort, Peter; van der Meer, Jos W. M.; Toni, Ivan

    2008-01-01

    Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease. Cognitive behavioural therapy (CBT) is an…

  8. Measuring the cortical silent period can increase diagnostic confidence for amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Schelhaas, H.J.; Arts, I.M.P.; Overeem, S.; Houtman, C.J.; Janssen, H.; Kleine, B.U.; Munneke, M.; Zwarts, M.J.

    2007-01-01

    We evaluated a modified measurement of the cortical silent period (CSP) as a simple procedure to add further confidence in the diagnostic work-up for ALS. Thirty-seven consecutive patients with a suspicion of having ALS were included together with 25 healthy volunteers, and followed until a final

  9. Increased Insular Cortical Thickness Associated With Symptom Severity in Male Youths With Internet Gaming Disorder: A Surface-Based Morphometric Study

    Science.gov (United States)

    Wang, Shuai; Liu, Jing; Tian, Lin; Chen, Limin; Wang, Jun; Tang, Qunfeng; Zhang, Fuquan; Zhou, Zhenhe

    2018-01-01

    With the rising increase in Internet-usage, Internet gaming disorder (IGD) has gained massive attention worldwide. However, detailed cerebral morphological changes remain unclear in youths with IGD. In the current study, our aim was to investigate cortical morphology and further explore the relationship between the cortical morphology and symptom severity in male youths with IGD. Forty-eight male youths with IGD and 32 age- and education-matched normal controls received magnetic resonance imaging scans. We employed a recently proposed surface-based morphometric approach for the measurement of cortical thickness (CT). We found that youths with IGD showed increased CT in the bilateral insulae and the right inferior temporal gyrus. Moreover, significantly decreased CT were found in several brain areas in youths with IGD, including the bilateral banks of the superior temporal sulci, the right inferior parietal cortex, the right precuneus, the right precentral gyrus, and the left middle temporal gyrus. Additionally, youths with IGD demonstrated a significantly positive correlation between the left insular CT and symptom severity. Our data provide evidence for the finding of abnormal CT in distributed cerebral areas and support the notion that altered structural abnormalities observed in substance addiction are also manifested in IGD. Such information extends current knowledge about IGD-related brain reorganization and could help future efforts in identifying the role of insula in the disorder. PMID:29666588

  10. Increased Insular Cortical Thickness Associated With Symptom Severity in Male Youths With Internet Gaming Disorder: A Surface-Based Morphometric Study

    Directory of Open Access Journals (Sweden)

    Shuai Wang

    2018-04-01

    Full Text Available With the rising increase in Internet-usage, Internet gaming disorder (IGD has gained massive attention worldwide. However, detailed cerebral morphological changes remain unclear in youths with IGD. In the current study, our aim was to investigate cortical morphology and further explore the relationship between the cortical morphology and symptom severity in male youths with IGD. Forty-eight male youths with IGD and 32 age- and education-matched normal controls received magnetic resonance imaging scans. We employed a recently proposed surface-based morphometric approach for the measurement of cortical thickness (CT. We found that youths with IGD showed increased CT in the bilateral insulae and the right inferior temporal gyrus. Moreover, significantly decreased CT were found in several brain areas in youths with IGD, including the bilateral banks of the superior temporal sulci, the right inferior parietal cortex, the right precuneus, the right precentral gyrus, and the left middle temporal gyrus. Additionally, youths with IGD demonstrated a significantly positive correlation between the left insular CT and symptom severity. Our data provide evidence for the finding of abnormal CT in distributed cerebral areas and support the notion that altered structural abnormalities observed in substance addiction are also manifested in IGD. Such information extends current knowledge about IGD-related brain reorganization and could help future efforts in identifying the role of insula in the disorder.

  11. A grape-enriched diet increases bone calcium retention and cortical bone properties in ovariectomized rats.

    Science.gov (United States)

    Hohman, Emily E; Weaver, Connie M

    2015-02-01

    Grapes and their associated phytochemicals have been investigated for beneficial effects on cardiovascular health, cancer prevention, and other chronic diseases, but the effect of grape consumption on bone health has not been fully determined. We previously found short-term benefits of grape products on reducing bone turnover in ovariectomized rats. The objective of this study was to determine the long-term benefits of a grape-enriched diet on bone in ovariectomized rats. Rats were ovariectomized at 3 mo of age and were administered a single dose of (45)Ca to prelabel bones at 4 mo of age. After a 1-mo equilibration period, baseline urinary (45)Ca excretion was determined. Rats (n = 22/group) were then randomly assigned to a modified AIN93M diet containing 25% freeze-dried grape powder or to a control diet for 8 wk. Urinary (45)Ca excretion was monitored throughout the study to determine changes in bone (45)Ca retention. Calcium balance was assessed after 1 and 8 wk of consuming the experimental diets, and a calcium kinetic study was performed at 8 wk. After 8 wk, femurs were collected for micro-computed tomographic imaging, 3-point bending, and reference point indentation. Rats fed the grape-enriched diet had 44% greater net bone calcium retention than did rats fed the control diet. There were no differences in calcium balance due to diet at either week 1 or week 8, but there was a significant increase in net calcium absorption (10.6%) and retention (5.7%) from week 1 to week 8 in the grape-enriched diet group only. Grape-enriched diet-fed rats had 3% greater cortical thickness and 11% greater breaking strength. There were no differences in femur bone mineral density, trabecular microarchitecture, or reference point indentation variables due to diet. This study of ovariectomized rats indicates that the consumption of grape products may improve calcium utilization and suppress bone turnover, resulting in improvements in bone quality. © 2015 American Society for

  12. Increased cortical curvature reflects white matter atrophy in individual patients with early multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Michael Deppe

    2014-01-01

    Conclusion: Whole-brain-averaged cortical extrinsic curvature appears to be a specific and quantitative marker for a WMV–cortex disproportionality and allows us to assess “pure” WMA without being confounded by intracranial volume. WMA seems to be a characteristic symptom in early MS and can already occur in patients with CIS and should thus be considered in future MS research and clinical studies.

  13. Reduced cortical thickness and increased surface area in antisocial personality disorder.

    Science.gov (United States)

    Jiang, Weixiong; Li, Gang; Liu, Huasheng; Shi, Feng; Wang, Tao; Shen, Celina; Shen, Hui; Lee, Seong-Whan; Hu, Dewen; Wang, Wei; Shen, Dinggang

    2016-11-19

    Antisocial personality disorder (ASPD), one of whose characteristics is high impulsivity, is of great interest in the field of brain structure and function. However, little is known about possible impairments in the cortical anatomy in ASPD, in terms of cortical thickness (CTh) and surface area (SA), as well as their possible relationship with impulsivity. In this neuroimaging study, we first investigated the changes of CTh and SA in ASPD patients, in comparison to those of healthy controls, and then performed correlation analyses between these measures and the ability of impulse control. We found that ASPD patients showed thinner cortex while larger SA in several specific brain regions, i.e., bilateral superior frontal gyrus (SFG), orbitofrontal and triangularis, insula cortex, precuneus, middle frontal gyrus (MFG), middle temporal gyrus (MTG), and left bank of superior temporal sulcus (STS). In addition, we also found that the ability of impulse control was positively correlated with CTh in the SFG, MFG, orbitofrontal cortex (OFC), pars triangularis, superior temporal gyrus (STG), and insula cortex. To our knowledge, this study is the first to reveal simultaneous changes in CTh and SA in ASPD, as well as their relationship with impulsivity. These cortical structural changes may introduce uncontrolled and callous behavioral characteristic in ASPD patients, and these potential biomarkers may be very helpful in understanding the pathomechanism of ASPD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Neuropeptide Y administration into the third ventricle does not increase sucrose or ethanol self-administration but does affect the cortical EEG and increases food intake.

    Science.gov (United States)

    Katner, S N; Slawecki, C J; Ehlers, C L

    2002-03-01

    Several studies have provided indirect evidence that neuropeptide Y (NPY) may play a role in the regulation of ethanol consumption. However, the direct effects of central NPY administration on ethanol drinking are unclear. This study examined the effects of NPY on ethanol, sucrose, and food consumption as well as its concomitant effects on the cortical EEG. Wistar rats were implanted with cortical recording electrodes and a cannula in the third ventricle after using a sucrose substitution procedure to establish ethanol self-administration. NPY (0-15 microg/3.0 microl) was infused into the third ventricle prior to drinking sessions, when 10% ethanol (10E), 2% sucrose (2S), 0.5% sucrose (0.5S), or food were available. Behavior and cortical EEG were monitored during the sessions. NPY had no effect on the intake of 10E, 2S, or 0.5S, but NPY (15 microg/3.0 microl) significantly increased food intake. Under baseline drinking conditions, EEG power in the 6-8 Hz range was significantly greater when 2S was consumed compared to 10E. NPY decreased power in the 8-16 Hz range, decreased peak frequency in the 6-8 Hz range, and increased peak frequency in the 32-50 Hz range when 10E or 2S was available. These data suggest that NPY administration into the third ventricle preferentially regulates feeding compared to ethanol or sucrose drinking. In addition, since NPY significantly altered the cortical EEG in the absence of effects on ethanol and sucrose consumption, these data may indicate that NPY's cortical EEG effects are more related to its sedative or anxiolytic properties, rather than any effect on consumption.

  15. Why Does Sleep Slow-Wave Activity Increase After Extended Wake? Assessing the Effects of Increased Cortical Firing During Wake and Sleep.

    Science.gov (United States)

    Rodriguez, Alexander V; Funk, Chadd M; Vyazovskiy, Vladyslav V; Nir, Yuval; Tononi, Giulio; Cirelli, Chiara

    2016-12-07

    During non-rapid eye movement (NREM) sleep, cortical neurons alternate between ON periods of firing and OFF periods of silence. This bi-stability, which is largely synchronous across neurons, is reflected in the EEG as slow waves. Slow-wave activity (SWA) increases with wake duration and declines homeostatically during sleep, but the underlying mechanisms remain unclear. One possibility is neuronal "fatigue": high, sustained firing in wake would force neurons to recover with more frequent and longer OFF periods during sleep. Another possibility is net synaptic potentiation during wake: stronger coupling among neurons would lead to greater synchrony and therefore higher SWA. Here, we obtained a comparable increase in sustained firing (6 h) in cortex by: (1) keeping mice awake by exposure to novel objects to promote plasticity and (2) optogenetically activating a local population of cortical neurons at wake-like levels during sleep. Sleep after extended wake led to increased SWA, higher synchrony, and more time spent OFF, with a positive correlation between SWA, synchrony, and OFF periods. Moreover, time spent OFF was correlated with cortical firing during prior wake. After local optogenetic stimulation, SWA and cortical synchrony decreased locally, time spent OFF did not change, and local SWA was not correlated with either measure. Moreover, laser-induced cortical firing was not correlated with time spent OFF afterward. Overall, these results suggest that high sustained firing per se may not be the primary determinant of SWA increases observed after extended wake. A long-standing hypothesis is that neurons fire less during slow-wave sleep to recover from the "fatigue" accrued during wake, when overall synaptic activity is higher than in sleep. This idea, however, has rarely been tested and other factors, namely increased cortical synchrony, could explain why sleep slow-wave activity (SWA) is higher after extended wake. We forced neurons in the mouse cortex to fire

  16. Demonstration of a setup for chronic optogenetic stimulation and recording across cortical areas in non-human primates

    Science.gov (United States)

    Yazdan-Shahmorad, Azadeh; Diaz-Botia, Camilo; Hanson, Tim; Ledochowitsch, Peter; Maharabiz, Michel M.; Sabes, Philip N.

    2015-03-01

    Although several studies have shown the feasibility of using optogenetics in non-human primates (NHP), reliable largescale chronic interfaces have not yet been reported for such studies in NHP. Here we introduce a chronic setup that permits repeated, daily optogenetic stimulation and large-scale recording from the same sites in NHP cortex. The setup combines optogenetics with a transparent artificial dura (AD) and high-density micro-electrocorticography (μECoG). To obtain expression across large areas of cortex, we infused AAV5-CamKIIa-C1V1-EYFP viral vector using an infusion technique based on convection-enhanced delivery (CED) in primary somatosensory (S1) and motor (M1) cortices. By epifluorescent imaging through AD we were able to confirm high levels of expression covering about 110 mm2 of S1 and M1. We then incorporated a 192-channel μECoG array spanning 192 mm2 into the AD for simultaneous electrophysiological recording during optical stimulation. The array consists of patterned Pt-Au-Pt metal traces embedded in ~10 μm Parylene-C insulator. The parylene is sufficiently transparent to allow minimally attenuated optical access for optogenetic stimulation. The array was chronically implanted over the opsin-expressing areas in M1 and S1 for over two weeks. Optical stimulation was delivered via a fiber optic placed on the surface of the AD. With this setup, we recorded reliable evoked activity following light stimulation at several locations. Similar responses were recorded across tens of days, however a decline in the light-evoked signal amplitude was observed during this period due to the growth of dural tissue over the array. These results show the feasibility of a chronic interface for combined largescale optogenetic stimulation and cortical recordings across days.

  17. Suberoylanilide hydroxamic acid increases progranulin production in iPSC-derived cortical neurons of frontotemporal dementia patients.

    Science.gov (United States)

    Almeida, Sandra; Gao, Fuying; Coppola, Giovanni; Gao, Fen-Biao

    2016-06-01

    Mutations in the granulin (GRN) gene cause frontotemporal dementia (FTD) due to progranulin haploinsufficiency. Compounds that can increase progranulin production and secretion may be considered as potential therapeutic drugs; however, very few of them have been directly tested on human cortical neurons. To this end, we differentiated 9 induced pluripotent stem cell lines derived from a control subject, a sporadic FTD case and an FTD patient with progranulin S116X mutation. Treatment with 1 μM suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, increased the production of progranulin in cortical neurons of all subjects at both the mRNA and protein levels without affecting their viability. Microarray analysis revealed that SAHA treatment not only reversed some gene expression changes caused by progranulin haploinsufficiency but also caused massive alterations in the overall transcriptome. Thus, histone deacetylase inhibitors may be considered as therapeutic drugs for GRN mutation carriers. However, this class of drugs also causes drastic changes in overall gene expression in human cortical neurons and their side effects and potential impacts on other pathways should be carefully evaluated. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. 34 CFR 377.1 - What is the Demonstration Projects to Increase Client Choice Program?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false What is the Demonstration Projects to Increase Client... PROJECTS TO INCREASE CLIENT CHOICE PROGRAM General § 377.1 What is the Demonstration Projects to Increase Client Choice Program? The Demonstration Projects to Increase Client Choice Program is designed to...

  19. Increased cortical thickness and altered functional connectivity of the right superior temporal gyrus in left-handers.

    Science.gov (United States)

    Li, Meiling; Chen, Heng; Wang, Junping; Liu, Feng; Wang, Yifeng; Lu, Fengmei; Yu, Chunshui; Chen, Huafu

    2015-01-01

    Altered structure in the temporal cortex has been implicated in the variable language laterality of left-handers (LH). The neuroanatomy of language lateralization and the corresponding synchronous functional connectivity (FC) in handedness cohorts are not, however, fully understood. We used structural and resting-state functional magnetic resonance imaging (fMRI) data to investigate the effect of altered cortical thickness on FC in LH and right-handers (RH). Whole-brain cortical thickness was calculated and compared between the LH and RH. We observed increased cortical thickness in the right superior temporal gyrus (STG) in the LH. A further FC analysis was conducted between the right STG and the remaining voxels in the brain. Compared with RH, the LH showed significantly higher FC in the left STG, right occipital cortex, and lower FC in the left inferior frontal gyrus and supramarginal gyrus. Our findings suggest that LH have atypical connectivity in the language network, with an enhanced role of the STG, findings which provide novel insights into the structural and functional substrates underlying the atypical language development of left-handed individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Cortical Visual Impairment

    Science.gov (United States)

    ... resolves by one year of life. Is “cortical blindness” the same thing as CVI? Cortical blindness is ... What visual characteristics are associated with CVI? • Distinct color preferences • Variable level of vision loss, often demonstrating ...

  1. Tibial loading increases osteogenic gene expression and cortical bone volume in mature and middle-aged mice.

    Directory of Open Access Journals (Sweden)

    Matthew J Silva

    Full Text Available There are conflicting data on whether age reduces the response of the skeleton to mechanical stimuli. We examined this question in female BALB/c mice of different ages, ranging from young to middle-aged (2, 4, 7, 12 months. We first assessed markers of bone turnover in control (non-loaded mice. Serum osteocalcin and CTX declined significantly from 2 to 4 months (p<0.001. There were similar age-related declines in tibial mRNA expression of osteoblast- and osteoclast-related genes, most notably in late osteoblast/matrix genes. For example, Col1a1 expression declined 90% from 2 to 7 months (p<0.001. We then assessed tibial responses to mechanical loading using age-specific forces to produce similar peak strains (-1300 µε endocortical; -2350 µε periosteal. Axial tibial compression was applied to the right leg for 60 cycles/day on alternate days for 1 or 6 weeks. qPCR after 1 week revealed no effect of loading in young (2-month mice, but significant increases in osteoblast/matrix genes in older mice. For example, in 12-month old mice Col1a1 was increased 6-fold in loaded tibias vs. controls (p = 0.001. In vivo microCT after 6 weeks revealed that loaded tibias in each age group had greater cortical bone volume (BV than contralateral control tibias (p<0.05, due to relative periosteal expansion. The loading-induced increase in cortical BV was greatest in 4-month old mice (+13%; p<0.05 vs. other ages. In summary, non-loaded female BALB/c mice exhibit an age-related decline in measures related to bone formation. Yet when subjected to tibial compression, mice from 2-12 months have an increase in cortical bone volume. Older mice respond with an upregulation of osteoblast/matrix genes, which increase to levels comparable to young mice. We conclude that mechanical loading of the tibia is anabolic for cortical bone in young and middle-aged female BALB/c mice.

  2. MDMA ‘ecstasy’ increases cerebral cortical perfusion determined by bolus-tracking arterial spin labelling (btASL) MRI

    Science.gov (United States)

    Rouine, J; Gobbo, O L; Campbell, M; Gigliucci, V; Ogden, I; McHugh Smith, K; Duffy, P; Behan, B; Byrne, D; Kelly, M E; Blau, C W; Kerskens, C M; Harkin, A

    2013-01-01

    Background and Purpose The purpose of this study was to assess cerebral perfusion changes following systemic administration of the recreational drug 3,4-methylendioxymethamphetamine (MDMA ‘ecstasy’) to rats. Experimental Approach Cerebral perfusion was quantified using bolus-tracking arterial spin labelling (btASL) MRI. Rats received MDMA (20 mg·kg−1; i.p.) and were assessed 1, 3 or 24 h later. Rats received MDMA (5 or 20 mg·kg−1; i.p.) and were assessed 3 h later. In addition, rats received MDMA (5 or 10 mg·kg−1; i.p.) or saline four times daily over 2 consecutive days and were assessed 8 weeks later. Perfusion-weighted images were generated in a 7 tesla (7T) MRI scanner and experimental data was fitted to a quantitative model of cerebral perfusion to generate mean transit time (MTT), capillary transit time (CTT) and signal amplitude. Key Results MDMA reduces MTT and CTT and increases amplitude in somatosensory and motor cortex 1 and 3 h following administration, indicative of an increase in perfusion. Prior exposure to MDMA provoked a long-term reduction in cortical 5-HT concentration, but did not produce a sustained effect on cerebral cortical perfusion. The response to acute MDMA challenge (20 mg·kg−1; i.p.) was attenuated in these animals indicating adaptation in response to prior MDMA exposure. Conclusions and Implications MDMA provokes changes in cortical perfusion, which are quantifiable by btASL MRI, a neuroimaging tool with translational potential. Future studies are directed towards elucidation of the mechanisms involved and correlating changes in cerebrovascular function with potential behavioural deficits associated with drug use. PMID:23517012

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

    Directory of Open Access Journals (Sweden)

    Cen Fu

    2015-04-01

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

  4. Risperidone increases the cortical silent period in drug-naive patients with first-episode schizophrenia: A transcranial magnetic stimulation study.

    Science.gov (United States)

    Ustohal, Libor; Mayerova, Michaela; Hublova, Veronika; Prikrylova Kucerova, Hana; Ceskova, Eva; Kasparek, Tomas

    2017-04-01

    Schizophrenia is accompanied by impaired cortical inhibition, as measured by several markers including the cortical silent period (CSP). It is thought that CSP measures gamma-aminobutyric acid receptors B (GABA B ) mediated inhibitory activity. But the mutual roles of schizophrenia as a disease and the drugs used for the treatment of psychosis on GABA mediated neurotransmission are not clear. We recruited 13 drug-naive patients with first-episode schizophrenia. We used transcranial magnetic stimulation to assess CSP prior to initiating risperidone monotherapy and again four weeks later. At the same time, we rated the severity of psychopathology using the Positive and Negative Syndrome Scale (PANSS). We obtained data from 12 patients who showed a significant increase in CSP, from 134.20±41.81 ms to 162.95±61.98 ms ( p=0.041; Cohen's d=0.544). After the treatment, the PANSS total score was significantly lower, as were the individual subscores ( pschizophrenia demonstrated an association between risperidone monotherapy and an increase in GABA B mediated inhibitory neurotransmission.

  5. Investigation of the mechanisms mediating MDMA "Ecstasy"-induced increases in cerebro-cortical perfusion determined by btASL MRI.

    Science.gov (United States)

    Rouine, J; Kelly, M E; Jennings-Murphy, C; Duffy, P; Gorman, I; Gormley, S; Kerskens, C M; Harkin, Andrew

    2015-05-01

    Acute administration of the recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has previously been shown to increase cerebro-cortical perfusion as determined by bolus-tracking arterial spin labelling (btASL) MRI. The purpose of the current study was to assess the mechanisms mediating these changes following systemic administration of MDMA to rats. Pharmacological manipulation of serotonergic, dopaminergic and nitrergic transmission was carried out to determine the mechanism of action of MDMA-induced increases in cortical perfusion using btASL MRI. Fenfluramine (10 mg/kg), like MDMA (20 mg/kg), increased cortical perfusion. Increased cortical perfusion was not obtained with the 5-HT2 receptor agonist 2,5-dimethoxy-4-iodophenyl-aminopropane hydrochloride (DOI) (1 mg/kg). Depletion of central 5-HT following systemic administration of the tryptophan hydroxylase inhibitor para-chlorophenylalanine (pCPA) produced effects similar to those observed with MDMA. Pre-treatment with the 5-HT receptor antagonist metergoline (4 mg/kg) or with the 5-HT reuptake inhibitor citalopram (30 mg/kg), however, failed to produce any effect alone or influence the response to MDMA. Pre-treatment with the dopamine D1 receptor antagonist SCH 23390 (1 mg/kg) failed to influence the changes in cortical perfusion obtained with MDMA. Treatment with the neuronal nitric oxide (NO) synthase inhibitor 7-nitroindazole (7-NI) (25 mg/kg) provoked no change in cerebral perfusion alone yet attenuated the MDMA-related increase in cortical perfusion. Cortical 5-HT depletion is associated with increases in perfusion although this mechanism alone does not account for MDMA-related changes. A role for NO, a key regulator of cerebrovascular perfusion, is implicated in MDMA-induced increases in cortical perfusion.

  6. Increased serum neuron specific enolase concentrations in patients with hyperglycemic cortical ischemic stroke

    NARCIS (Netherlands)

    Elting, JW; De Keyser, J; Sulter, G.

    1998-01-01

    A detrimental effect of hyperglycemia in ischemic brain has been demonstrated in laboratory experiments and it has been found that hyperglycemia in ischemic stroke is a predictor of poor outcome. We determined serum neuron specific enolase (NSE) concentrations in 41 consecutive patients with a

  7. Neural basis of moral elevation demonstrated through inter-subject synchronization of cortical activity during free-viewing.

    Directory of Open Access Journals (Sweden)

    Zoë A Englander

    Full Text Available Most research investigating the neural basis of social emotions has examined emotions that give rise to negative evaluations of others (e.g. anger, disgust. Emotions triggered by the virtues and excellences of others have been largely ignored. Using fMRI, we investigated the neural basis of two "other-praising" emotions--Moral Elevation (a response to witnessing acts of moral beauty, and Admiration (which we restricted to admiration for physical skill.Ten participants viewed the same nine video clips. Three clips elicited moral elevation, three elicited admiration, and three were emotionally neutral. We then performed pair-wise voxel-by-voxel correlations of the BOLD signal between individuals for each video clip and a separate resting-state run. We observed a high degree of inter-subject synchronization, regardless of stimulus type, across several brain regions during free-viewing of videos. Videos in the elevation condition evoked significant inter-subject synchronization in brain regions previously implicated in self-referential and interoceptive processes, including the medial prefrontal cortex, precuneus, and insula. The degree of synchronization was highly variable over the course of the videos, with the strongest synchrony occurring during portions of the videos that were independently rated as most emotionally arousing. Synchrony in these same brain regions was not consistently observed during the admiration videos, and was absent for the neutral videos.Results suggest that the neural systems supporting moral elevation are remarkably consistent across subjects viewing the same emotional content. We demonstrate that model-free techniques such as inter-subject synchronization may be a useful tool for studying complex, context dependent emotions such as self-transcendent emotion.

  8. Cortical oxygenation suggests increased effort during cognitive inhibition in ecstasy polydrug users.

    Science.gov (United States)

    Roberts, C A; Montgomery, Catharine

    2015-11-01

    It is understood that 3,4-methylenedioxymethamphetamine (ecstasy) causes serotonin dysfunction and deficits in executive functioning. When investigating executive function, functional neuroimaging allows the physiological changes underlying these deficits to be investigated. The present study investigated behavioural and brain indices of inhibition in ecstasy-polydrug users. Twenty ecstasy-polydrug users and 20 drug-naïve participants completed an inhibitory control task (Random Letter Generation (RLG)) while prefrontal haemodynamic response was assessed using functional near infrared spectroscopy (fNIRS). There were no group differences on background measures including sleep quality and mood state. There were also no behavioural differences between the two groups. However, ecstasy-polydrug users displayed significant increases in oxygenated haemoglobin (oxy-Hb) from baseline compared to controls at several voxels relating to areas of the inferior right medial prefrontal cortex, as well the right and left dorsolateral prefrontal cortex. Regression analysis revealed that recency of ecstasy use was a significant predictor of oxy-Hb increase at two voxels over the right hemisphere after controlling for alcohol and cannabis use indices. Ecstasy-polydrug users show increased neuronal activation in the prefrontal cortex compared to non-users. This is taken to be compensatory activation/recruitment of additional resources to attain similar performance levels on the task, which may be reversible with prolonged abstinence. © The Author(s) 2015.

  9. rTMS Induced Tinnitus Relief Is Related to an Increase in Auditory Cortical Alpha Activity

    Science.gov (United States)

    Müller, Nadia; Lorenz, Isabel; Langguth, Berthold; Weisz, Nathan

    2013-01-01

    Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom. A promising approach for the treatment of tinnitus is repetitive transcranial magnetic stimulation (rTMS) as this directly affects tinnitus-related brain activity. Several studies indeed show tinnitus relief after rTMS, however effects are moderate and vary strongly across patients. This may be due to a lack of knowledge regarding how rTMS affects oscillatory activity in tinnitus sufferers and which modulations are associated with tinnitus relief. In the present study we examined the effects of five different stimulation protocols (including sham) by measuring tinnitus loudness and tinnitus-related brain activity with Magnetoencephalography before and after rTMS. Changes in oscillatory activity were analysed for the stimulated auditory cortex as well as for the entire brain regarding certain frequency bands of interest (delta, theta, alpha, gamma). In line with the literature the effects of rTMS on tinnitus loudness varied strongly across patients. This variability was also reflected in the rTMS effects on oscillatory activity. Importantly, strong reductions in tinnitus loudness were associated with increases in alpha power in the stimulated auditory cortex, while an unspecific decrease in gamma and alpha power, particularly in left frontal regions, was linked to an increase in tinnitus loudness. The identification of alpha power increase as main correlate for tinnitus reduction sheds further light on the pathophysiology of tinnitus. This will hopefully stimulate the development of more effective therapy approaches. PMID:23390539

  10. Increasing seat belt use through state-level demonstration projects : a compendium of initial findings

    Science.gov (United States)

    2008-08-01

    This report summarizes the efforts and results from four of six State-level demonstration projects supported with cooperative agreements from the National Highway Traffic Safety Administration. The projects were intended to increase seat belt use sta...

  11. Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength.

    Science.gov (United States)

    Sinder, B P; White, L E; Salemi, J D; Ominsky, M S; Caird, M S; Marini, J C; Kozloff, K M

    2014-08-01

    Treatments to reduce fracture rates in adults with osteogenesis imperfecta are limited. Sclerostin antibody, developed for treating osteoporosis, has not been explored in adults with OI. This study demonstrates that treatment of adult OI mice respond favorably to sclerostin antibody therapy despite retention of the OI-causing defect. Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk. Although OI fracture risk is greatest before puberty, adults with OI remain at risk of fracture. Antiresorptive bisphosphonates are commonly used to treat adult OI, but have shown mixed efficacy. New treatments which consistently improve bone mass throughout the skeleton may improve patient outcomes. Neutralizing antibodies to sclerostin (Scl-Ab) are a novel anabolic therapy that have shown efficacy in preclinical studies by stimulating bone formation via the canonical wnt signaling pathway. The purpose of this study was to evaluate Scl-Ab in an adult 6 month old Brtl/+ model of OI that harbors a typical heterozygous OI-causing Gly > Cys substitution on Col1a1. Six-month-old WT and Brtl/+ mice were treated with Scl-Ab (25 mg/kg, 2×/week) or Veh for 5 weeks. OCN and TRACP5b serum assays, dynamic histomorphometry, microCT and mechanical testing were performed. Adult Brtl/+ mice demonstrated a strong anabolic response to Scl-Ab with increased serum osteocalcin and bone formation rate. This anabolic response led to improved trabecular and cortical bone mass in the femur. Mechanical testing revealed Scl-Ab increased Brtl/+ femoral stiffness and strength. Scl-Ab was successfully anabolic in an adult Brtl/+ model of OI.

  12. Increased reward in ankle robotics training enhances motor control and cortical efficiency in stroke.

    Science.gov (United States)

    Goodman, Ronald N; Rietschel, Jeremy C; Roy, Anindo; Jung, Brian C; Diaz, Jason; Macko, Richard F; Forrester, Larry W

    2014-01-01

    Robotics is rapidly emerging as a viable approach to enhance motor recovery after disabling stroke. Current principles of cognitive motor learning recognize a positive relationship between reward and motor learning. Yet no prior studies have established explicitly whether reward improves the rate or efficacy of robotics-assisted rehabilitation or produces neurophysiologic adaptations associated with motor learning. We conducted a 3 wk, 9-session clinical pilot with 10 people with chronic hemiparetic stroke, randomly assigned to train with an impedance-controlled ankle robot (anklebot) under either high reward (HR) or low reward conditions. The 1 h training sessions entailed playing a seated video game by moving the paretic ankle to hit moving onscreen targets with the anklebot only providing assistance as needed. Assessments included paretic ankle motor control, learning curves, electroencephalograpy (EEG) coherence and spectral power during unassisted trials, and gait function. While both groups exhibited changes in EEG, the HR group had faster learning curves (p = 0.05), smoother movements (p increase in nonparetic step length (p = 0.05) in the HR group only. These results suggest that combining explicit rewards with novel anklebot training may accelerate motor learning for restoring mobility.

  13. Focal cortical hypoperfusion in corticobasal degeneration demonstrated by three-dimensional surface display with {sup 123}I-IMP: a possible cause of apraxia

    Energy Technology Data Exchange (ETDEWEB)

    Okuda, B. [5. Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Tachibana, H. [5. Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Takeda, M. [5. Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Kawabata, K. [5. Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Sugita, M. [5. Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya (Japan); Fukuchi, M. [Department of Nuclear Medicine, Hyogo College of Medicine, Nishinomiya (Japan)

    1995-11-01

    To clarify cortical lesions responsible for apraxia in corticobasal degeneration (CBD), we reconstructed three-dimensional surface images from single-photon emission computed tomography (SPECT) data with N-isopropyl-p[I-123]-iodoamphetamine in two patients with CBD. Both had limb-kinetic apraxia (LKA) and one also had constructional apraxia (CA). Both showed asymmetrical cortical hypoperfusion in the perirolandic area. The patient with CA had unilateral hypoperfusion in the posterior parietal area. Thus, cortical hypoperfusion in the perirolandic area corresponded to LKA, and that in the posterior parietal area to CA. (orig.). With 4 figs.

  14. Focal cortical hypoperfusion in corticobasal degeneration demonstrated by three-dimensional surface display with 123I-IMP: a possible cause of apraxia

    International Nuclear Information System (INIS)

    Okuda, B.; Tachibana, H.; Takeda, M.; Kawabata, K.; Sugita, M.; Fukuchi, M.

    1995-01-01

    To clarify cortical lesions responsible for apraxia in corticobasal degeneration (CBD), we reconstructed three-dimensional surface images from single-photon emission computed tomography (SPECT) data with N-isopropyl-p[I-123]-iodoamphetamine in two patients with CBD. Both had limb-kinetic apraxia (LKA) and one also had constructional apraxia (CA). Both showed asymmetrical cortical hypoperfusion in the perirolandic area. The patient with CA had unilateral hypoperfusion in the posterior parietal area. Thus, cortical hypoperfusion in the perirolandic area corresponded to LKA, and that in the posterior parietal area to CA. (orig.). With 4 figs

  15. Increased Cortical Inhibition in Autism-Linked Neuroligin-3R451C Mice Is Due in Part to Loss of Endocannabinoid Signaling.

    Science.gov (United States)

    Speed, Haley E; Masiulis, Irene; Gibson, Jay R; Powell, Craig M

    2015-01-01

    A single, maternally inherited, X-linked point mutation leading to an arginine to cysteine substitution at amino acid 451 (R451C) of Neuroligin 3 (NLGN3R451C) is a likely cause of autism in two brothers. Knockin mice expressing the Nlgn3R451C mutation in place of wild-type Nlgn3 demonstrate increased inhibitory synaptic strength in somatosensory cortex, resulting in an excitatory/inhibitory (E/I) imbalance that is potentially relevant for autism-associated behavioral deficits characteristic of these mice. We have replicated the increase in evoked inhibitory postsynaptic currents (eIPSCs) onto layer II/III cortical pyramidal neurons. We also find that increased frequency of spontaneous mIPSCs in Nlgn3R451C mice occurs in the absence of action potential-driven transmission. This suggests the E/I imbalance is due to changes at the synapse level, as opposed to the network level. Next, we use paired whole-cell recordings in an attempt to identify specific interneuron subtypes affected by the Nlgn3R451C mutation. Curiously, we observe no change in the amplitude of cell-to-cell, unitary IPSCs (uIPSCs) from parvalbumin-positive (PV) or somatostatin-positive (SOM) interneurons onto pyramidal neurons. We also observe no change in the number or density of PV and SOM interneurons in LII/III of somatosensory cortex. This effectively rules out a role for these particular interneurons in the increased inhibitory synaptic transmission, pointing to perhaps alternative interneuron subtypes. Lastly, impaired endocannabinoid signaling has been implicated in hippocampal synaptic dysfunction in Nlgn3R451C mice, but has not been investigated at cortical synapses. We find that bath application of the CB1 antagonist, AM 251 in WT mice eliminates the Nlgn3R451C increase in eIPSC amplitude and mIPSC frequency, indicating that increased inhibitory transmission in mutant mice is due, at least in part, to a loss of endocannabinoid signaling through CB1 receptors likely acting at interneurons

  16. Increased Cortical Inhibition in Autism-Linked Neuroligin-3R451C Mice Is Due in Part to Loss of Endocannabinoid Signaling.

    Directory of Open Access Journals (Sweden)

    Haley E Speed

    Full Text Available A single, maternally inherited, X-linked point mutation leading to an arginine to cysteine substitution at amino acid 451 (R451C of Neuroligin 3 (NLGN3R451C is a likely cause of autism in two brothers. Knockin mice expressing the Nlgn3R451C mutation in place of wild-type Nlgn3 demonstrate increased inhibitory synaptic strength in somatosensory cortex, resulting in an excitatory/inhibitory (E/I imbalance that is potentially relevant for autism-associated behavioral deficits characteristic of these mice. We have replicated the increase in evoked inhibitory postsynaptic currents (eIPSCs onto layer II/III cortical pyramidal neurons. We also find that increased frequency of spontaneous mIPSCs in Nlgn3R451C mice occurs in the absence of action potential-driven transmission. This suggests the E/I imbalance is due to changes at the synapse level, as opposed to the network level. Next, we use paired whole-cell recordings in an attempt to identify specific interneuron subtypes affected by the Nlgn3R451C mutation. Curiously, we observe no change in the amplitude of cell-to-cell, unitary IPSCs (uIPSCs from parvalbumin-positive (PV or somatostatin-positive (SOM interneurons onto pyramidal neurons. We also observe no change in the number or density of PV and SOM interneurons in LII/III of somatosensory cortex. This effectively rules out a role for these particular interneurons in the increased inhibitory synaptic transmission, pointing to perhaps alternative interneuron subtypes. Lastly, impaired endocannabinoid signaling has been implicated in hippocampal synaptic dysfunction in Nlgn3R451C mice, but has not been investigated at cortical synapses. We find that bath application of the CB1 antagonist, AM 251 in WT mice eliminates the Nlgn3R451C increase in eIPSC amplitude and mIPSC frequency, indicating that increased inhibitory transmission in mutant mice is due, at least in part, to a loss of endocannabinoid signaling through CB1 receptors likely acting at

  17. Assessing denoising strategies to increase signal to noise ratio in spinal cord and in brain cortical and subcortical regions

    Science.gov (United States)

    Maugeri, L.; Moraschi, M.; Summers, P.; Favilla, S.; Mascali, D.; Cedola, A.; Porro, C. A.; Giove, F.; Fratini, M.

    2018-02-01

    Functional Magnetic Resonance Imaging (fMRI) based on Blood Oxygenation Level Dependent (BOLD) contrast has become one of the most powerful tools in neuroscience research. On the other hand, fMRI approaches have seen limited use in the study of spinal cord and subcortical brain regions (such as the brainstem and portions of the diencephalon). Indeed obtaining good BOLD signal in these areas still represents a technical and scientific challenge, due to poor control of physiological noise and to a limited overall quality of the functional series. A solution can be found in the combination of optimized experimental procedures at acquisition stage, and well-adapted artifact mitigation procedures in the data processing. In this framework, we studied two different data processing strategies to reduce physiological noise in cortical and subcortical brain regions and in the spinal cord, based on the aCompCor and RETROICOR denoising tools respectively. The study, performed in healthy subjects, was carried out using an ad hoc isometric motor task. We observed an increased signal to noise ratio in the denoised functional time series in the spinal cord and in the subcortical brain region.

  18. Prefrontal cortical parvalbumin and somatostatin expression and cell density increase during adolescence and are modified by BDNF and sex.

    Science.gov (United States)

    Du, X; Serena, K; Hwang, W; Grech, A M; Wu, Y W C; Schroeder, A; Hill, R A

    2018-04-01

    Brain-derived neurotrophic factor (BDNF) is known to play a critical role early in the development of cortical GABAergic interneurons. Recently our laboratory and others have shown protracted development of specific subpopulations of GABAergic interneurons extending into adolescence. BDNF expression also changes significantly across adolescent development. However the role of BDNF in regulating GABAergic changes across adolescence remains unclear. Here, we performed a week-by-week analysis of the protein expression and cell density of three major GABAergic interneurons, parvalbumin (PV), somatostatin (SST) and calretinin (Cal) in the medial prefrontal cortex from prepubescence (week 3) to adulthood (week 12). In order to assess how BDNF and sex might influence the adolescent trajectory of GABAergic interneurons we compared WT as well as BDNF heterozygous (+/-) male and female mice. In both males and females PV expression increases during adolescent development in the mPFC. Compared to wild-types, PV expression was reduced in male but not female BDNF+/- mice throughout adolescent development. This reduction in protein expression corresponded with reduced cell density, specifically within the infralimbic prefrontal cortex. SST expression increased in early adolescent WT females and this upregulation was delayed in BDNF+/-. SST cell density also increased in early adolescent mPFC of WT female mice, with BDNF+/- again showing a reduced pattern of expression. Cal protein expression was also sex-dependently altered across adolescence with WT males showing a steady decline but that of BDNF+/- remaining unaltered. Reduced cell density in on the other hand was observed particularly in male BDNF+/- mice. In females, Cal protein expression and cell density remained largely stable. Our results show that PV, SST and calretinin interneurons are indeed still developing into early adolescence in the mPFC and that BDNF plays a critical, sex-specific role in mediating expression and

  19. Evaluation of a rural demonstration program to increase seat belt use in the Great Lakes Region.

    Science.gov (United States)

    2009-03-01

    Six States in the Great Lakes Region (Region 5) participated in a Rural Demonstration Program to increase seat belt : use in rural areas and among high-risk occupants, such as young males and occupants of pickup trucks. These : efforts, which include...

  20. Long-term lithium treatment increases intracellular and extracellular brain-derived neurotrophic factor (BDNF) in cortical and hippocampal neurons at subtherapeutic concentrations.

    Science.gov (United States)

    De-Paula, Vanessa J; Gattaz, Wagner F; Forlenza, Orestes V

    2016-12-01

    The putative neuroprotective effects of lithium treatment rely on the fact that it modulates several homeostatic mechanisms involved in the neurotrophic response, autophagy, oxidative stress, inflammation, and mitochondrial function. Lithium is a well-established therapeutic option for the acute and long-term management of bipolar disorder and major depression. The aim of this study was to evaluate the effects of subtherapeutic and therapeutic concentrations of chronic lithium treatment on brain-derived neurotrophic factor (BDNF) synthesis and secretion. Primary cultures of cortical and hippocampal neurons were treated with different subtherapeutic (0.02 and 0.2 mM) and therapeutic (2 mM) concentrations of chronic lithium treatment in cortical and hippocampal cell culture. Lithium treatment increased the intracellular protein expression of cortical neurons (10% at 0.02 mM) and hippocampal neurons (28% and 14% at 0.02 mM and 0.2 mM, respectively). Extracellular BDNF of cortical neurons increased 30% and 428% at 0.02 and 0.2 mM, respectively and in hippocampal neurons increased 44% at 0.02 mM. The present study indicates that chronic, low-dose lithium treatment up-regulates BDNF production in primary neuronal cell culture. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Extent of cortical involvement in amyotrophic lateral sclerosis--an analysis based on cortical thickness.

    Science.gov (United States)

    Thorns, Johannes; Jansma, Henk; Peschel, Thomas; Grosskreutz, Julian; Mohammadi, Bahram; Dengler, Reinhard; Münte, Thomas F

    2013-10-18

    Besides the defining involvement of upper and lower motor neurons, the involvement of extramotor structures has been increasingly acknowledged in amyotrophic lateral sclerosis (ALS). Here we investigated a group of 14 mildly to moderately affected ALS patients and 14 age-matched healthy control participants using cortical thickness analysis. Cortical thickness was determined from high resolution 3D T1 magnetic resonance images and involved semiautomatic segmentation in grey and white matter, cortical alignment and determination of thickness using the Laplace method. In addition to a whole-cortex analysis a region of interest approach was applied. ALS patients showed regions of significant cortical thinning in the pre- and postcentral gyri bilaterally. Further regions of cortical thinning included superior and inferior parietal lobule, angular and supramarginal gyrus, insula, superior frontal, temporal and occipital regions, thus further substantiating extramotor involvement in ALS. A relationship between cortical thickness of the right superior frontal cortex and clinical severity (assessed by the ALS functional rating scale) was also demonstrated. Cortical thickness is reduced in ALS not only in motor areas but in widespread non-motor cortical areas. Cortical thickness is related to clinical severity.

  2. Implicit sequence-specific motor learning after sub-cortical stroke is associated with increased prefrontal brain activations: An fMRI study

    Science.gov (United States)

    Meehan, Sean K.; Randhawa, Bubblepreet; Wessel, Brenda; Boyd, Lara A.

    2010-01-01

    Implicit motor learning is preserved after stroke, but how the brain compensates for damage to facilitate learning is unclear. We used a random effects analysis to determine how stroke alters patterns of brain activity during implicit sequence-specific motor learning as compared to general improvements in motor control. Nine healthy participants and 9 individuals with chronic, right focal sub-cortical stroke performed a continuous joystick-based tracking task during an initial fMRI session, over 5 days of practice, and a retention test during a separate fMRI session. Sequence-specific implicit motor learning was differentiated from general improvements in motor control by comparing tracking performance on a novel, repeated tracking sequences during early practice and again at the retention test. Both groups demonstrated implicit sequence-specific motor learning at the retention test, yet substantial differences were apparent. At retention, healthy control participants demonstrated increased BOLD response in left dorsal premotor cortex (BA 6) but decreased BOLD response left dorsolateral prefrontal cortex (DLPFC; BA 9) during repeated sequence tracking. In contrast, at retention individuals with stroke did not show this reduction in DLPFC during repeated tracking. Instead implicit sequence-specific motor learning and general improvements in motor control were associated with increased BOLD response in the left middle frontal gyrus BA 8, regardless of sequence type after stroke. These data emphasize the potential importance of a prefrontal-based attentional network for implicit motor learning after stroke. The present study is the first to highlight the importance of the prefrontal cortex for implicit sequence-specific motor learning after stroke. PMID:20725908

  3. Perceived stress is associated with increased rostral middle frontal gyrus cortical thickness: a family-based and discordant-sibling investigation.

    Science.gov (United States)

    Michalski, L J; Demers, C H; Baranger, D A A; Barch, D M; Harms, M P; Burgess, G C; Bogdan, R

    2017-11-01

    Elevated stress perception and depression commonly co-occur, suggesting that they share a common neurobiology. Cortical thickness of the rostral middle frontal gyrus (RMFG), a region critical for executive function, has been associated with depression- and stress-related phenotypes. Here, we examined whether RMFG cortical thickness is associated with these phenotypes in a large family-based community sample. RMFG cortical thickness was estimated using FreeSurfer among participants (n = 879) who completed the ongoing Human Connectome Project. Depression-related phenotypes (i.e. sadness, positive affect) and perceived stress were assessed via self-report. After accounting for sex, age, ethnicity, average whole-brain cortical thickness, twin status and familial structure, RMFG thickness was positively associated with perceived stress and sadness and negatively associated with positive affect at small effect sizes (accounting for 0.2-2.4% of variance; p-fdr: 0.0051-0.1900). Perceived stress was uniquely associated with RMFG thickness after accounting for depression-related phenotypes. Further, among siblings discordant for perceived stress, those reporting higher perceived stress had increased RMFG thickness (P = 4 × 10 -7 ). Lastly, RMFG thickness, perceived stress, depressive symptoms, and positive affect were all significantly heritable, with evidence of shared genetic and environmental contributions between self-report measures. Stress perception and depression share common genetic, environmental, and neural correlates. Variability in RMFG cortical thickness may play a role in stress-related depression, although effects may be small in magnitude. Prospective studies are required to examine whether variability in RMFG thickness may function as a risk factor for stress exposure and/or perception, and/or arises as a consequence of these phenotypes. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  4. Increased cerebrospinal fluid albumin and immunoglobulin A fractions forecast cortical atrophy and longitudinal functional deterioration in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Kroth, Julia; Ciolac, Dumitru; Fleischer, Vinzenz; Koirala, Nabin; Krämer, Julia; Muthuraman, Muthuraman; Luessi, Felix; Bittner, Stefan; Gonzalez-Escamilla, Gabriel; Zipp, Frauke; Meuth, Sven G; Groppa, Sergiu

    2017-12-01

    Currently, no unequivocal predictors of disease evolution exist in patients with multiple sclerosis (MS). Cortical atrophy measurements are, however, closely associated with cumulative disability. Here, we aim to forecast longitudinal magnetic resonance imaging (MRI)-driven cortical atrophy and clinical disability from cerebrospinal fluid (CSF) markers. We analyzed CSF fractions of albumin and immunoglobulins (Ig) A, G, and M and their CSF to serum quotients. Widespread atrophy was highly associated with increased baseline CSF concentrations and quotients of albumin and IgA. Patients with increased CSF IgA and CSF IgM showed higher functional disability at follow-up. CSF markers of blood-brain barrier integrity and specific immune response forecast emerging gray matter pathology and disease progression in MS.

  5. Repairing the brain with physical exercise: Cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention

    Directory of Open Access Journals (Sweden)

    Kamila U. Szulc-Lerch

    Full Text Available There is growing evidence that exercise induced experience dependent plasticity may foster structural and functional recovery following brain injury. We examined the efficacy of exercise training for neural and cognitive recovery in long-term pediatric brain tumor survivors treated with radiation.We conducted a controlled clinical trial with crossover of exercise training (vs. no training in a volunteer sample of 28 children treated with cranial radiation for brain tumors (mean age = 11.5 yrs.; mean time since diagnosis = 5.7 yrs. The endpoints were anatomical T1 MRI data and multiple behavioral outcomes presenting a broader analysis of structural MRI data across the entire brain. This included an analysis of changes in cortical thickness and brain volume using automated, user unbiased approaches. A series of general linear mixed effects models evaluating the effects of exercise training on cortical thickness were performed in a voxel and vertex-wise manner, as well as for specific regions of interest. In exploratory analyses, we evaluated the relationship between changes in cortical thickness after exercise with multiple behavioral outcomes, as well as the relation of these measures at baseline.Exercise was associated with increases in cortical thickness within the right pre and postcentral gyri. Other notable areas of increased thickness related to training were present in the left pre and postcentral gyri, left temporal pole, left superior temporal gyrus, and left parahippocampal gyrus. Further, we observed that compared to a separate cohort of healthy children, participants displayed multiple areas with a significantly thinner cortex prior to training and fewer differences following training, indicating amelioration of anatomical deficits. Partial least squares analysis (PLS revealed specific patterns of relations between cortical thickness and various behavioral outcomes both after training and at baseline.Overall, our results

  6. Comparative Analysis of Bone Structural Parameters Reveals Subchondral Cortical Plate Resorption and Increased Trabecular Bone Remodeling in Human Facet Joint Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Cordula Netzer

    2018-03-01

    Full Text Available Facet joint osteoarthritis is a prominent feature of degenerative spine disorders, highly prevalent in ageing populations, and considered a major cause for chronic lower back pain. Since there is no targeted pharmacological therapy, clinical management of disease includes analgesic or surgical treatment. The specific cellular, molecular, and structural changes underpinning facet joint osteoarthritis remain largely elusive. The aim of this study was to determine osteoarthritis-related structural alterations in cortical and trabecular subchondral bone compartments. To this end, we conducted comparative micro computed tomography analysis in healthy (n = 15 and osteoarthritic (n = 22 lumbar facet joints. In osteoarthritic joints, subchondral cortical plate thickness and porosity were significantly reduced. The trabecular compartment displayed a 42 percent increase in bone volume fraction due to an increase in trabecular number, but not trabecular thickness. Bone structural alterations were associated with radiological osteoarthritis severity, mildly age-dependent but not gender-dependent. There was a lack of association between structural parameters of cortical and trabecular compartments in healthy and osteoarthritic specimens. The specific structural alterations suggest elevated subchondral bone resorption and turnover as a potential treatment target in facet joint osteoarthritis.

  7. Cortical thickness abnormalities in late adolescence with online gaming addiction.

    Science.gov (United States)

    Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M; Liu, Yijun; Qin, Wei; Tian, Jie

    2013-01-01

    Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction.

  8. State-dependent intrinsic predictability of cortical network dynamics.

    Directory of Open Access Journals (Sweden)

    Leila Fakhraei

    Full Text Available The information encoded in cortical circuit dynamics is fleeting, changing from moment to moment as new input arrives and ongoing intracortical interactions progress. A combination of deterministic and stochastic biophysical mechanisms governs how cortical dynamics at one moment evolve from cortical dynamics in recently preceding moments. Such temporal continuity of cortical dynamics is fundamental to many aspects of cortex function but is not well understood. Here we study temporal continuity by attempting to predict cortical population dynamics (multisite local field potential based on its own recent history in somatosensory cortex of anesthetized rats and in a computational network-level model. We found that the intrinsic predictability of cortical dynamics was dependent on multiple factors including cortical state, synaptic inhibition, and how far into the future the prediction extends. By pharmacologically tuning synaptic inhibition, we obtained a continuum of cortical states with asynchronous population activity at one extreme and stronger, spatially extended synchrony at the other extreme. Intermediate between these extremes we observed evidence for a special regime of population dynamics called criticality. Predictability of the near future (10-100 ms increased as the cortical state was tuned from asynchronous to synchronous. Predictability of the more distant future (>1 s was generally poor, but, surprisingly, was higher for asynchronous states compared to synchronous states. These experimental results were confirmed in a computational network model of spiking excitatory and inhibitory neurons. Our findings demonstrate that determinism and predictability of network dynamics depend on cortical state and the time-scale of the dynamics.

  9. Cortical thickness abnormalities in late adolescence with online gaming addiction.

    Directory of Open Access Journals (Sweden)

    Kai Yuan

    Full Text Available Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18 and age-, education- and gender-matched controls (n = 18 were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC, insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction.

  10. The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans.

    Science.gov (United States)

    Cortes-Briones, Jose A; Cahill, John D; Skosnik, Patrick D; Mathalon, Daniel H; Williams, Ashley; Sewell, R Andrew; Roach, Brian J; Ford, Judith M; Ranganathan, Mohini; D'Souza, Deepak Cyril

    2015-12-01

    Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Δ(9)-THC), the principal active constituent of cannabis. Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Δ(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. Δ(9)-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Δ(9)-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ(9)-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms. At doses that produced psychosis-like effects, Δ(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ(9)-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Δ(9)-THC. Published by Elsevier Inc.

  11. Repairing the brain with physical exercise: Cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention.

    Science.gov (United States)

    Szulc-Lerch, Kamila U; Timmons, Brian W; Bouffet, Eric; Laughlin, Suzanne; de Medeiros, Cynthia B; Skocic, Jovanka; Lerch, Jason P; Mabbott, Donald J

    2018-01-01

    There is growing evidence that exercise induced experience dependent plasticity may foster structural and functional recovery following brain injury. We examined the efficacy of exercise training for neural and cognitive recovery in long-term pediatric brain tumor survivors treated with radiation. We conducted a controlled clinical trial with crossover of exercise training (vs. no training) in a volunteer sample of 28 children treated with cranial radiation for brain tumors (mean age = 11.5 yrs.; mean time since diagnosis = 5.7 yrs). The endpoints were anatomical T1 MRI data and multiple behavioral outcomes presenting a broader analysis of structural MRI data across the entire brain. This included an analysis of changes in cortical thickness and brain volume using automated, user unbiased approaches. A series of general linear mixed effects models evaluating the effects of exercise training on cortical thickness were performed in a voxel and vertex-wise manner, as well as for specific regions of interest. In exploratory analyses, we evaluated the relationship between changes in cortical thickness after exercise with multiple behavioral outcomes, as well as the relation of these measures at baseline. Exercise was associated with increases in cortical thickness within the right pre and postcentral gyri. Other notable areas of increased thickness related to training were present in the left pre and postcentral gyri, left temporal pole, left superior temporal gyrus, and left parahippocampal gyrus. Further, we observed that compared to a separate cohort of healthy children, participants displayed multiple areas with a significantly thinner cortex prior to training and fewer differences following training, indicating amelioration of anatomical deficits. Partial least squares analysis (PLS) revealed specific patterns of relations between cortical thickness and various behavioral outcomes both after training and at baseline. Overall, our results indicate that

  12. Curved reformat of the paediatric brain MRI into a 'flat-earth map' - standardised method for demonstrating cortical surface atrophy resulting from hypoxic-ischaemic encephalopathy.

    Science.gov (United States)

    Simpson, Ewan; Andronikou, Savvas; Vedajallam, Schadie; Chacko, Anith; Thai, Ngoc Jade

    2016-09-01

    Hypoxic-ischaemic encephalopathy is optimally imaged with brain MRI in the neonatal period. However neuroimaging is often also performed later in childhood (e.g., when parents seek compensation in cases of alleged birth asphyxia). We describe a standardised technique for creating two curved reconstructions of the cortical surface to show the characteristic surface changes of hypoxic-ischaemic encephalopathy in children imaged after the neonatal period. The technique was applied for 10 cases of hypoxic-ischaemic encephalopathy and also for age-matched healthy children to assess the visibility of characteristic features of hypoxic-ischaemic encephalopathy. In the abnormal brains, fissural or sulcal widening was seen in all cases and ulegyria was identifiable in 7/10. These images could be used as a visual aid for communicating MRI findings to clinicians and other interested parties.

  13. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Laser-scanning astrocyte mapping reveals increased glutamate-responsive domain size and disrupted maturation of glutamate uptake following neonatal cortical freeze-lesion

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    Mortiz eArmbruster

    2014-09-01

    Full Text Available Astrocytic uptake of glutamate shapes extracellular neurotransmitter dynamics, receptor activation, and synaptogenesis. During development, glutamate transport becomes more robust. How neonatal brain insult affects the functional maturation of glutamate transport remains unanswered. Neonatal brain insult can lead to developmental delays, cognitive losses, and epilepsy; the disruption of glutamate transport is known to cause changes in synaptogenesis, receptor activation, and seizure. Using the neonatal freeze-lesion (FL model, we have investigated how insult affects the maturation of astrocytic glutamate transport. As lesioning occurs on the day of birth, a time when astrocytes are still functionally immature, this model is ideal for identifying changes in astrocyte maturation following insult. Reactive astrocytosis, astrocyte proliferation, and in vitro hyperexcitability are known to occur in this model. To probe astrocyte glutamate transport with better spatial precision we have developed a novel technique, Laser Scanning Astrocyte Mapping (LSAM, which combines glutamate transport current (TC recording from astrocytes with laser scanning glutamate photolysis. LSAM allows us to identify the area from which a single astrocyte can transport glutamate and to quantify spatial heterogeneity in the rate of glutamate clearance kinetics within that domain. Using LSAM, we report that cortical astrocytes have an increased glutamate-responsive area following FL and that TCs have faster decay times in distal, as compared to proximal processes. Furthermore, the developmental shift from GLAST- to GLT-1-dominated clearance is disrupted following FL. These findings introduce a novel method to probe astrocyte glutamate uptake and show that neonatal cortical FL disrupts the functional maturation of cortical astrocytes.

  15. A new model of strabismic amblyopia: Loss of spatial acuity due to increased temporal dispersion of geniculate X-cell afferents on to cortical neurons.

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    Crewther, D P; Crewther, S G

    2015-09-01

    Although the neural locus of strabismic amblyopia has been shown to lie at the first site of binocular integration, first in cat and then in primate, an adequate mechanism is still lacking. Here we hypothesise that increased temporal dispersion of LGN X-cell afferents driven by the deviating eye onto single cortical neurons may provide a neural mechanism for strabismic amblyopia. This idea was investigated via single cell extracellular recordings of 93 X and 50 Y type LGN neurons from strabismic and normal cats. Both X and Y neurons driven by the non-deviating eye showed shorter latencies than those driven by either the strabismic or normal eyes. Also the mean latency difference between X and Y neurons was much greater for the strabismic cells compared with the other two groups. The incidence of lagged X-cells driven by the deviating eye of the strabismic cats was higher than that of LGN X-cells from normal animals. Remarkably, none of the cells recorded from the laminae driven by the non-deviating eye were of the lagged class. A simple computational model was constructed in which a mixture of lagged and non-lagged afferents converge on to single cortical neurons. Model cut-off spatial frequencies to a moving grating stimulus were sensitive to the temporal dispersion of the geniculate afferents. Thus strabismic amblyopia could be viewed as a lack of developmental tuning of geniculate lags for neurons driven by the amblyopic eye. Monocular control of fixation by the non-deviating eye is associated with reduced incidence of lagged neurons, suggesting that in normal vision, lagged neurons might play a role in maintaining binocular connections for cortical neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Effects of low intensity pulsed ultrasound with and without increased cortical porosity on structural bone allograft incorporation

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    Ehrhart Nicole

    2008-05-01

    Full Text Available Abstract Background Though used for over a century, structural bone allografts suffer from a high rate of mechanical failure due to limited graft revitalization even after extended periods in vivo. Novel strategies that aim to improve graft incorporation are lacking but necessary to improve the long-term clinical outcome of patients receiving bone allografts. The current study evaluated the effect of low-intensity pulsed ultrasound (LIPUS, a potent exogenous biophysical stimulus used clinically to accelerate the course of fresh fracture healing, and longitudinal allograft perforations (LAP as non-invasive therapies to improve revitalization of intercalary allografts in a sheep model. Methods Fifteen skeletally-mature ewes were assigned to five experimental groups based on allograft type and treatment: +CTL, -CTL, LIPUS, LAP, LIPUS+LAP. The +CTL animals (n = 3 received a tibial ostectomy with immediate replacement of the resected autologous graft. The -CTL group (n = 3 received fresh frozen ovine tibial allografts. The +CTL and -CTL groups did not receive LAP or LIPUS treatments. The LIPUS treatment group (n = 3, following grafting with fresh frozen ovine tibial allografts, received ultrasound stimulation for 20 minutes/day, 5 days/week, for the duration of the healing period. The LAP treatment group (n = 3 received fresh frozen ovine allografts with 500 μm longitudinal perforations that extended 10 mm into the graft. The LIPUS+LAP treatment group (n = 3 received both LIPUS and LAP interventions. All animals were humanely euthanized four months following graft transplantation for biomechanical and histological analysis. Results After four months of healing, daily LIPUS stimulation of the host-allograft junctions, alone or in combination with LAP, resulted in 30% increases in reconstruction stiffness, paralleled by significant increases (p Conclusion The current study has demonstrated in a large animal model the potential of both LIPUS and LAP

  17. Increased Cortical Gamma-Aminobutyric Acid Precedes Incomplete Extinction of Conditioned Fear and Increased Hippocampal Excitatory Tone in a Mouse Model of Mild Traumatic Brain Injury.

    Science.gov (United States)

    Schneider, Brandy L; Ghoddoussi, Farhad; Charlton, Jennifer L; Kohler, Robert J; Galloway, Matthew P; Perrine, Shane A; Conti, Alana C

    2016-09-01

    Mild traumatic brain injury (mTBI) contributes to development of affective disorders, including post-traumatic stress disorder (PTSD). Psychiatric symptoms typically emerge in a tardive fashion post-TBI, with negative effects on recovery. Patients with PTSD, as well as rodent models of PTSD, demonstrate structural and functional changes in brain regions mediating fear learning, including prefrontal cortex (PFC), amygdala (AMYG), and hippocampus (HC). These changes may reflect loss of top-down control by which PFC normally exhibits inhibitory influence over AMYG reactivity to fearful stimuli, with HC contribution. Considering the susceptibility of these regions to injury, we examined fear conditioning (FC) in the delayed post-injury period, using a mouse model of mTBI. Mice with mTBI displayed enhanced acquisition and delayed extinction of FC. Using proton magnetic resonance spectroscopy ex vivo, we examined PFC, AMYG, and HC levels of gamma-aminobutyric acid (GABA) and glutamate as surrogate measures of inhibitory and excitatory neurotransmission, respectively. Eight days post-injury, GABA was increased in PFC, with no significant changes in AMYG. In animals receiving FC and mTBI, glutamate trended toward an increase and the GABA/glutamate ratio decreased in ventral HC at 25 days post-injury, whereas GABA decreased and GABA/glutamate decreased in dorsal HC. These neurochemical changes are consistent with early TBI-induced PFC hypoactivation facilitating the fear learning circuit and exacerbating behavioral fear responses. The latent emergence of overall increased excitatory tone in the HC, despite distinct plasticity in dorsal and ventral HC fields, may be associated with disordered memory function, manifested as incomplete extinction and enhanced FC recall.

  18. Identification of a brainstem circuit regulating visual cortical state in parallel with locomotion.

    Science.gov (United States)

    Lee, A Moses; Hoy, Jennifer L; Bonci, Antonello; Wilbrecht, Linda; Stryker, Michael P; Niell, Cristopher M

    2014-07-16

    Sensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and increases in the gain of cortical responses. MLR stimulation below the threshold for overt movement similarly changed cortical processing, revealing that MLR's effects on cortex are dissociable from locomotion. Likewise, stimulation of MLR projections to the basal forebrain also enhanced cortical responses, suggesting a pathway linking the MLR to cortex. These studies demonstrate that the MLR regulates cortical state in parallel with locomotion. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMAIII) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression.

    Science.gov (United States)

    Escudero-Lourdes, C; Uresti-Rivera, E E; Oliva-González, C; Torres-Ramos, M A; Aguirre-Bañuelos, P; Gandolfi, A J

    2016-10-01

    Long-term exposure to inorganic arsenic (iAs) through drinking water has been associated with cognitive impairment in children and adults; however, the related pathogenic mechanisms have not been completely described. Increased or chronic inflammation in the brain is linked to impaired cognition and neurodegeneration; iAs induces strong inflammatory responses in several cells, but this effect has been poorly evaluated in central nervous system (CNS) cells. Because astrocytes are the most abundant cells in the CNS and play a critical role in brain homeostasis, including regulation of the inflammatory response, any functional impairment in them can be deleterious for the brain. We propose that iAs could induce cognitive impairment through inflammatory response activation in astrocytes. In the present work, rat cortical astrocytes were acutely exposed in vitro to the monomethylated metabolite of iAs (MMA III ), which accumulates in glial cells without compromising cell viability. MMA III LD 50 in astrocytes was 10.52 μM, however, exposure to sub-toxic MMA III concentrations (50-1000 nM) significantly increased IL-1β, IL-6, TNF-α, COX-2, and MIF-1 gene expression. These effects were consistent with amyloid precursor protein (APP) and β-secretase (BACE-1) increased gene expression, mainly for those MMA III concentrations that also induced TNF-α over-expression. Other effects of MMA III on cortical astrocytes included increased proliferative and metabolic activity. All tested MMA III concentrations led to an inhibition of intracellular lactate dehydrogenase (LDH) activity. Results suggest that MMA III induces important metabolic and functional changes in astrocytes that may affect brain homeostasis and that inflammation may play a major role in cognitive impairment-related pathogenicity in As-exposed populations.

  20. Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Ibrahim M Salman

    2015-08-01

    Full Text Available Chronic kidney disease (CKD is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n=16 were instrumented for telemetric recording of RSNA and MAP. At 12–13 weeks-of-age, resting RSNA and MAP, sympathetic and haemodynamic responses to both peripheral (hypoxia: 10% O2 and central chemoreflex (hypercapnia: 7% CO2 activation and acute stress (open-field exposure, were measured. As indicators of renal function, urinary protein (UPro and creatinine (Ucr levels were assessed. LPK rats had higher resting RSNA (1.2±0.1 vs. 0.6±0.1 µV, p<0.05 and MAP (151±8 vs. 97±2 mmHg, p<0.05 compared to Lewis. MAP was negatively correlated with Ucr (r=-0.80, p=0.002 and positively correlated with RSNA (r=0.66, p=0.014, with multiple linear regression modeling indicating the strongest correlation was with Ucr. RSNA and MAP responses to activation of the central chemoreflex and open-field stress were reduced in the LPK relative to the Lewis (all p<0.05. This is the first description of dual conscious telemetry recording of RSNA and MAP in a genetic rodent model of CKD. Elevated RSNA is likely a key contributor to the marked hypertension in this model, while attenuated RSNA and MAP responses to central chemoreflex activation and acute stress in the LPK indicate possible deficits in the neural processing of autonomic outflows evoked by these sympathoexcitatory pathways.

  1. Increasing the Understanding and Demonstration of Appropriate Affection in Children with Asperger Syndrome: A Pilot Trial

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    Kate Sofronoff

    2011-01-01

    Full Text Available The study was conducted to examine relationships between affectionate behavior in children with Asperger syndrome and variables likely to influence its expression (e.g., tactile sensitivity, social ability. It also evaluated the impact of a cognitive behavioral intervention that aimed to improve a child's understanding and expression of affection. Twenty-one children, aged 7 to 12 years, participated in the trial. The results showed significant correlations between measures of affection and tactile sensitivity and social ability. After attending the 5-week program, parents identified significant increases in the appropriateness of children's affectionate behavior both towards immediate family and people outside the immediate family, despite reporting no significant changes in their child's general difficulties with affectionate behavior. There was a significant improvement in children's understanding of the purpose of affection. The findings are discussed as well as the limitations of the study.

  2. Field demonstration of age dependent increase in lead phytoextraction by Pelargonium cultivar

    Science.gov (United States)

    Shahid, Muhammad; Arshad, Muhammad; Pinelli, Eric; Alric, Alain; Kaemmerer, Michel; Pradere, Philippe; Dumat, Camille

    2013-04-01

    Unnecessary for living organisms, lead (Pb) is one of the major widespread toxic metals found in the environment with potential danger to human health and to ecosystems (Shahid et al. 2012). Lead is known to induce a broad range of toxic effects to living organism, including those that are morphological, physiological and biochemical in origin (Pourrut et al. 2011). A field study was carried out in the vicinity of Pb recycling plant near Toulouse-France, and contaminated by atmospheric fallouts to evaluate lead extraction and uptake efficiency of hyperaccumulater Attar of Roses Pelargonium cultivar. It was found that Attar of Roses has ability to accumulate (8644 mgPb/kg DW plant) and survive on highly contaminated acidic soil (39250 mg kg-1 of total Pb) without any morpho-phytotoxicity symptoms. Moreover Attar showed increased extraction of lead from bulk soil to rhizosphere through Pb mobilization and ultimately increased uptake by roots and translocation to shoots. The studied contaminated soil could be cleaned up in few years by planting hyperaccumulater Attar of Rose for longer time period. Under optimum fertlization, irrigation and use of natural or synthetic chelates (EDTA, LMOWA, humic substances etc.) along with old Attar of rose plants, time requires for complete remediation of contaminated site can be reduced to practically applicable time period. Moreover, the use of Pelargonium for remediation has several additional practical, esthetical and economic advantages. The extraction of value-added essential oils from harvested biomass could offset the cost of deploying phytoremediation and renders it as a viable approach for remediating highly contaminated soils, on large scale. Keywords: metal uptake, Pelargonium, phytoremediation, cultivar, soil-plant transfer and kinetic. References Pourrut, B., Shahid, M., Dumat, C., Winterton, P., Pinelli, E., 2011a. Lead uptake, toxicity and detoxification in plants. Rev. Environ. Contam. Toxicol. 213, 113-136. Shahid

  3. Using Wavelet Entropy to Demonstrate how Mindfulness Practice Increases Coordination between Irregular Cerebral and Cardiac Activities.

    Science.gov (United States)

    Sik, Hin Hung; Gao, Junling; Fan, Jicong; Wu, Bonnie Wai Yan; Leung, Hang Kin; Hung, Yeung Sam

    2017-05-10

    In both the East and West, traditional teachings say that the mind and heart are somehow closely correlated, especially during spiritual practice. One difficulty in proving this objectively is that the natures of brain and heart activities are quite different. In this paper, we propose a methodology that uses wavelet entropy to measure the chaotic levels of both electroencephalogram (EEG) and electrocardiogram (ECG) data and show how this may be used to explore the potential coordination between the mind and heart under different experimental conditions. Furthermore, Statistical Parametric Mapping (SPM) was used to identify the brain regions in which the EEG wavelet entropy was the most affected by the experimental conditions. As an illustration, the EEG and ECG were recorded under two different conditions (normal rest and mindful breathing) at the beginning of an 8-week standard Mindfulness-based Stress Reduction (MBSR) training course (pretest) and after the course (posttest). Using the proposed method, the results consistently showed that the wavelet entropy of the brain EEG decreased during the MBSR mindful breathing state as compared to that during the closed-eye resting state. Similarly, a lower wavelet entropy of heartrate was found during MBSR mindful breathing. However, no difference in wavelet entropy during MBSR mindful breathing was found between the pretest and posttest. No correlation was observed between the entropy of brain waves and the entropy of heartrate during normal rest in all participants, whereas a significant correlation was observed during MBSR mindful breathing. Additionally, the most well-correlated brain regions were located in the central areas of the brain. This study provides a methodology for the establishment of evidence that mindfulness practice (i.e., mindful breathing) may increase the coordination between mind and heart activities.

  4. Mice with GFAP-targeted loss of neurofibromin demonstrate increased axonal MET expression with aging.

    Science.gov (United States)

    Su, Weiping; Xing, Rubing; Guha, Abhijit; Gutmann, David H; Sherman, Larry S

    2007-05-01

    Neurofibromatosis 1 (NF1) is a common genetic disease that predisposes patients to peripheral nerve tumors and central nervous system (CNS) abnormalities including low-grade astrocytomas and cognitive disabilities. Using mice with glial fibrillary acidic protein (GFAP)-targeted Nf1 loss (Nf1(GFAP)CKO mice), we found that Nf1(-/-) astrocytes proliferate faster and are more invasive than wild-type astrocytes. In light of our previous finding that aberrant expression of the MET receptor tyrosine kinase contributes to the invasiveness of human NF1-associated malignant peripheral nerve sheath tumors, we sought to determine whether MET expression is aberrant in the brains of Nf1 mutant mice. We found that Nf1(-/-) astrocytes express slightly more MET than wild-type cells in vitro, but do not express elevated MET in situ. However, fiber tracts containing myelinated axons in the hippocampus, midbrain, cerebral cortex, and cerebellum express higher than normal levels of MET in older (> or =6 months) Nf1(GFAP)CKO mice. Both Nf1(GFAP)CKO and wild-type astrocytes induced MET expression in neurites of wild-type hippocampal neurons in vitro, suggesting that astrocyte-derived signals may induce MET in Nf1 mutant mice. Because the Nf1 gene product functions as a RAS GTPase, we examined MET expression in the brains of mice with GFAP-targeted constitutively active forms of RAS. MET was elevated in axonal fiber tracts in mice with active K-RAS but not H-RAS. Collectively, these data suggest that loss of Nf1 in either astrocytes or GFAP(+) neural progenitor cells results in increased axonal MET expression, which may contribute to the CNS abnormalities in children and adults with NF1. (c) 2007 Wiley-Liss, Inc.

  5. Summer anesthesiology externship: Demonstrating the ability of early clinical involvement to educate and increase specialty interest.

    Science.gov (United States)

    Baker, Kevin S; Cormican, Daniel; Seidman, Peggy A

    2012-01-01

    We describe the influence of a 6-week "Summer Anesthesiology Externship" featuring didactic, procedure, and simulation education on formation of medical students' specialty choice. Eighteen months after externship completion, externs were sent a questionnaire with Likert scale agreement ratings of subspecialties/simulations and yes/no questions about student career interests before/after the program, stipend importance, and procedural skill performance during/after the program. General anesthesiology had the highest subspecialty approval rating (9.0). Externs strongly agreed that simulations successfully progressed at first year student understanding levels (9.2 mean agreement rating), increased confidence in being part of a care team (9.4 mean agreement rating), and provided personal/interpersonal development. Externs unanimously agreed that the program introduced them to the breadth of anesthesiology, and that practicing clinical/procedural skills improved confidence when performing the procedures later in medical school. Four of 14 students applied for the externship with some focus on anesthesiology as a career choice. After the externship, a significantly higher number of students (12 of 14) were strongly considering applying to the field (prate than our general medical student classes (p<0.0001). Both CA1 and CA3 resident post-test scores improved at the end of the ultrasound guided regional workshop. Our study showed a 68% improvement in test scores, which is larger than the 50% improvement previously reported. These results show that fast learning can occur in this type of setting. Furthermore, knowledge acquired during the workshop was retained when CA1 residents were re-tested one year after the workshop. The ultrasound-guided regional anesthesia workshop will become part of the didactic series for our CA1 residents and will be a required learning activity. Additional work still needs to be done to find out the best way to test knowledge and skill

  6. Acute hepatic encephalopathy presenting as cortical laminar necrosis: Case report

    International Nuclear Information System (INIS)

    Choi, Jong Mun; Kim, Yoon Hee; Roh, Sook Young

    2013-01-01

    We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.

  7. Acute hepatic encephalopathy presenting as cortical laminar necrosis: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jong Mun; Kim, Yoon Hee; Roh, Sook Young [Bundang Jesaeng General Hospital, Daejin Medical Center, Seongnam (Korea, Republic of)

    2013-04-15

    We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.

  8. Increased overall cortical connectivity with syndrome specific local decreases suggested by atypical sleep-EEG synchronization in Williams syndrome.

    Science.gov (United States)

    Gombos, Ferenc; Bódizs, Róbert; Kovács, Ilona

    2017-07-21

    Williams syndrome (7q11.23 microdeletion) is characterized by specific alterations in neurocognitive architecture and functioning, as well as disordered sleep. Here we analyze the region, sleep state and frequency-specific EEG synchronization of whole night sleep recordings of 21 Williams syndrome and 21 typically developing age- and gender-matched subjects by calculating weighted phase lag indexes. We found broadband increases in inter- and intrahemispheric neural connectivity for both NREM and REM sleep EEG of Williams syndrome subjects. These effects consisted of increased theta, high sigma, and beta/low gamma synchronization, whereas alpha synchronization was characterized by a peculiar Williams syndrome-specific decrease during NREM states (intra- and interhemispheric centro-temporal) and REM phases of sleep (occipital intra-area synchronization). We also found a decrease in short range, occipital connectivity of NREM sleep EEG theta activity. The striking increased overall synchronization of sleep EEG in Williams syndrome subjects is consistent with the recently reported increase in synaptic and dendritic density in stem-cell based Williams syndrome models, whereas decreased alpha and occipital connectivity might reflect and underpin the altered microarchitecture of primary visual cortex and disordered visuospatial functioning of Williams syndrome subjects.

  9. Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

    Science.gov (United States)

    Espinosa, Nelson; Alonso, Alejandra; Morales, Cristian; Espinosa, Pedro; Chávez, Andrés E; Fuentealba, Pablo

    2017-11-17

    The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Menstrual endometrial cells from women with endometriosis demonstrate increased adherence to peritoneal cells and increased expression of CD44 splice variants.

    Science.gov (United States)

    Griffith, Jason S; Liu, Ya-Guang; Tekmal, Rajeshwar R; Binkley, Peter A; Holden, Alan E C; Schenken, Robert S

    2010-04-01

    We previously demonstrated that adherence of endometrial epithelial (EECs) and stromal cells (ESCs) to peritoneal mesothelial cells (PMCs) is partly regulated by ESC/EEC CD44 interactions with PMC associated hyaluronan. CD44, a transmembrane glycoprotein and major ligand for hyaluronan, has numerous splice variants which may impact hyaluronan binding. Here, we assessed whether ESCs and EECs from women with endometriosis demonstrate increased adherence to PMCs and examined CD44 splice variants' potential role in this process. In vitro study. Academic medical center. Fertility patients with and without endometriosis. Menstrual endometrium was collected from women with and without endometriosis confirmed surgically. The adherence of ESC/EECs to PMCs was measured. The ESC/EEC CD44 splice variants were assessed using dot-blot analysis. The ESCs and EECs from women with endometriosis demonstrated increased adherence to PMCs. The predominant CD44 splice variants expressed by ESCs and EECs from women with and without endometriosis were v3, v6, v7, v8, v9, and v10. The ESCs and EECs from women with endometriosis were more likely to express v6, v7, v8, and v9. Increased eutopic endometrial-PMC adherence and CD44 splice variant expression may contribute to the histogenesis of endometriotic lesions. Elucidation of factors controlling this expression may lead to novel endometriosis therapies. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice.

    Science.gov (United States)

    Beccano-Kelly, Dayne A; Kuhlmann, Naila; Tatarnikov, Igor; Volta, Mattia; Munsie, Lise N; Chou, Patrick; Cao, Li-Ping; Han, Heather; Tapia, Lucia; Farrer, Matthew J; Milnerwood, Austen J

    2014-01-01

    Mutations in Leucine-Rich Repeat Kinase-2 (LRRK2) result in familial Parkinson's disease and the G2019S mutation alone accounts for up to 30% in some ethnicities. Despite this, the function of LRRK2 is largely undetermined although evidence suggests roles in phosphorylation, protein interactions, autophagy and endocytosis. Emerging reports link loss of LRRK2 to altered synaptic transmission, but the effects of the G2019S mutation upon synaptic release in mammalian neurons are unknown. To assess wild type and mutant LRRK2 in established neuronal networks, we conducted immunocytochemical, electrophysiological and biochemical characterization of >3 week old cortical cultures of LRRK2 knock-out, wild-type overexpressing and G2019S knock-in mice. Synaptic release and synapse numbers were grossly normal in LRRK2 knock-out cells, but discretely reduced glutamatergic activity and reduced synaptic protein levels were observed. Conversely, synapse density was modestly but significantly increased in wild-type LRRK2 overexpressing cultures although event frequency was not. In knock-in cultures, glutamate release was markedly elevated, in the absence of any change to synapse density, indicating that physiological levels of G2019S LRRK2 elevate probability of release. Several pre-synaptic regulatory proteins shown by others to interact with LRRK2 were expressed at normal levels in knock-in cultures; however, synapsin 1 phosphorylation was significantly reduced. Thus, perturbations to the pre-synaptic release machinery and elevated synaptic transmission are early neuronal effects of LRRK2 G2019S. Furthermore, the comparison of knock-in and overexpressing cultures suggests that one copy of the G2019S mutation has a more pronounced effect than an ~3-fold increase in LRRK2 protein. Mutant-induced increases in transmission may convey additional stressors to neuronal physiology that may eventually contribute to the pathogenesis of Parkinson's disease.

  12. [Schizophrenia and cortical GABA neurotransmission].

    Science.gov (United States)

    Hashimoto, Takanori; Matsubara, Takuro; Lewis, David A

    2010-01-01

    -synaptic GABA-A receptors. Our recent analyses demonstrated that this pattern exists across diverse cortical areas including the prefrontal, anterior cingulate, primary motor, and primary visual cortices. GABA neurotransmission by PV-containing and SST-containing neurons is important for the generation of cortical oscillatory activities in the gamma (30-100 Hz) and theta (4-7 Hz) bands, respectively. These oscillatory activities have been proposed to play critical roles in regulating the efficiency of information transfer between neurons and neuronal networks in the cortex. Altered cortical GABA neurotransmission appears to contribute to disturbances in diverse functions through affecting the generation of cortical oscillations in schizophrenia.

  13. Six months of disuse during hibernation does not increase intracortical porosity or decrease cortical bone geometry, strength, or mineralization in black bear (Ursus americanus) femurs.

    Science.gov (United States)

    McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N; Drummer, Thomas D; Bunnell, Kevin; Auger, Janene; Black, Hal L; Donahue, Seth W

    2009-07-22

    Disuse typically uncouples bone formation from resorption, leading to bone loss which compromises bone mechanical properties and increases the risk of bone fracture. Previous studies suggest that bears can prevent bone loss during long periods of disuse (hibernation), but small sample sizes have limited the conclusions that can be drawn regarding the effects of hibernation on bone structure and strength in bears. Here we quantified the effects of hibernation on structural, mineral, and mechanical properties of black bear (Ursus americanus) cortical bone by studying femurs from large groups of male and female bears (with wide age ranges) killed during pre-hibernation (fall) and post-hibernation (spring) periods. Bone properties that are affected by body mass (e.g. bone geometrical properties) tended to be larger in male compared to female bears. There were no differences (p>0.226) in bone structure, mineral content, or mechanical properties between fall and spring bears. Bone geometrical properties differed by less than 5% and bone mechanical properties differed by less than 10% between fall and spring bears. Porosity (fall: 5.5+/-2.2%; spring: 4.8+/-1.6%) and ash fraction (fall: 0.694+/-0.011; spring: 0.696+/-0.010) also showed no change (p>0.304) between seasons. Statistical power was high (>72%) for these analyses. Furthermore, bone geometrical properties and ash fraction (a measure of mineral content) increased with age and porosity decreased with age. These results support the idea that bears possess a biological mechanism to prevent disuse and age-related osteoporoses.

  14. Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

    Energy Technology Data Exchange (ETDEWEB)

    Eneh, C. T. M., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Töyräs, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Jurvelin, J. S., E-mail: jukka.jurvelin@uef.fi [Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, Finland and Diagnostic Imaging Center, Kuopio University Hospital, P.O. Box 100, Kuopio FI-70029 (Finland); Malo, M. K. H., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Liukkonen, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi [Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211 (Finland); Karjalainen, J. P., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi [Bone Index Finland Ltd., P.O. Box 1188, Kuopio FI-70211 (Finland)

    2016-05-15

    Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessment by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R{sup 2} ≥ 0.493, p < 0.01 and R{sup 2} ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated

  15. Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

    International Nuclear Information System (INIS)

    Eneh, C. T. M.; Töyräs, J.; Jurvelin, J. S.; Malo, M. K. H.; Liukkonen, J.; Karjalainen, J. P.

    2016-01-01

    Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessment by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R"2 ≥ 0.493, p < 0.01 and R"2 ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated in vivo

  16. Increased 20-HETE synthesis explains reduced cerebral blood flow but not impaired neurovascular coupling after cortical spreading depression in rat cerebral cortex

    DEFF Research Database (Denmark)

    Fordsmann, Jonas Christoffer; ko, Rebecca; Choi, Hyun B

    2013-01-01

    Cortical spreading depression (CSD) is associated with release of arachidonic acid (AA), impaired neurovascular coupling, and reduced cerebral blood flow (CBF), caused by cortical vasoconstriction. We tested the hypothesis that the released AA is metabolized by the cytochrome P450 enzyme to produce...... neurovascular coupling after CSD. These findings suggest that CSD-induced increments in 20-HETE cause the reduction in CBF after CSD, and that the attenuation of stimulation-induced CBF responses after CSD has a different mechanism. We suggest that blockade of 20-HETE synthesis may be clinically relevant...

  17. Nrdp1 Increases Ischemia Induced Primary Rat Cerebral Cortical Neurons and Pheochromocytoma Cells Apoptosis Via Downregulation of HIF-1α Protein

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    2017-09-01

    Full Text Available Neuregulin receptor degradation protein-1 (Nrdp1 is an E3 ubiquitin ligase that targets proteins for degradation and regulates cell growth, apoptosis and oxidative stress in various cell types. We have previously shown that Nrdp1 is implicated in ischemic cardiomyocyte death. In this study, we investigated the change of Nrdp1 expression in ischemic neurons and its role in ischemic neuronal injury. Primary rat cerebral cortical neurons and pheochromocytoma (PC12 cells were infected with adenoviral constructs expressing Nrdp1 gene or its siRNA before exposing to oxygen-glucose deprivation (OGD treatment. Our data showed that Nrdp1 was upregulated in ischemic brain tissue 3 h after middle cerebral artery occlusion (MCAO and in OGD-treated neurons. Of note, Nrdp1 overexpression by Ad-Nrdp1 enhanced OGD-induced neuron apoptosis, while knockdown of Nrdp1 with siRNA attenuated this effect, implicating a role of Nrdp1 in ischemic neuron injury. Moreover, Nrdp1 upregulation is accompanied by increased protein ubiquitylation and decreased protein levels of ubiquitin-specific protease 8 (USP8 in OGD-treated neurons, which led to a suppressed interaction between USP8 and HIF-1α and subsequently a reduction in HIF-1α protein accumulation in neurons under OGD conditions. In conclusion, our data support an important role of Nrdp1 upregulation in ischemic neuronal death, and suppressing the interaction between USP8 and HIF-1α and consequently the hypoxic adaptive response of neurons may account for this detrimental effect.

  18. Increased bone marrow blood flow in sickle cell anemia demonstrated by thallium-201 and Tc-99m human albumin microspheres

    International Nuclear Information System (INIS)

    Thrall, J.H.; Rucknagel, D.L.

    1978-01-01

    Lower extremity vascularity in nine patients with sickle cell anemia was studied by intra-arterial /sup 99m/Tc human albumin microspheres or intravenous thallium-201. In eight patients, the normal pattern of greater muscle than bone activity was reversed with marked tracer localization in skeletal parts usually not visualized. In four cases, there were distinct focal abnormalities in the femurs and tibias which correlated with defects on /sup 99m/Tc sulfur colloid marrow scans. TC-99m pyrophosphate bone scans demonstrated normal uptake in the same areas. The scintigraphic findings indicate a markedly increased relative bone marrow blood flow

  19. Apolipoprotein E Mimetic Peptide Increases Cerebral Glucose Uptake by Reducing Blood-Brain Barrier Disruption after Controlled Cortical Impact in Mice: An 18F-Fluorodeoxyglucose PET/CT Study.

    Science.gov (United States)

    Qin, Xinghu; You, Hong; Cao, Fang; Wu, Yue; Peng, Jianhua; Pang, Jinwei; Xu, Hong; Chen, Yue; Chen, Ligang; Vitek, Michael P; Li, Fengqiao; Sun, Xiaochuan; Jiang, Yong

    2017-02-15

    Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and reduces cerebral glucose uptake. Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI, and COG1410 has demonstrated neuroprotective activity in several models of TBI. However, the effects of COG1410 on VEGF and glucose metabolism following TBI are unknown. The current study aimed to investigate the expression of VEGF and glucose metabolism effects in C57BL/6J male mice subjected to experimental TBI. The results showed that controlled cortical impact (CCI)-induced vestibulomotor deficits were accompanied by increases in brain edema and the expression of VEGF, with a decrease in cerebral glucose uptake. COG1410 treatment significantly improved vestibulomotor deficits and glucose uptake and produced decreases in VEGF in the pericontusion and ipsilateral hemisphere of injury, as well as in brain edema and neuronal degeneration compared with the control group. These data support that COG1410 may have potential as an effective drug therapy for TBI.

  20. Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity.

    Science.gov (United States)

    Astrand, Annika; Bohlooly-Y, Mohammad; Larsdotter, Sara; Mahlapuu, Margit; Andersén, Harriet; Tornell, Jan; Ohlsson, Claes; Snaith, Mike; Morgan, David G A

    2004-10-01

    Melanin-concentrating hormone (MCH) plays an important role in energy balance. The current studies were carried out on a new line of mice lacking the rodent MCH receptor (MCHR1(-/-) mice). These mice confirmed the previously reported lean phenotype characterized by increased energy expenditure and modestly increased caloric intake. Because MCH is expressed in the lateral hypothalamic area, which also has an important role in the regulation of the autonomic nervous system, heart rate and blood pressure were measured by a telemetric method to investigate whether the increased energy expenditure in these mice might be due to altered autonomic nervous system activity. Male MCHR1(-/-) mice demonstrated a significantly increased heart rate [24-h period: wild type 495 +/- 4 vs. MCHR1(-/-) 561 +/- 8 beats/min (P dark phase: wild type 506 +/- 8 vs. MCHR1(-/-) 582 +/- 9 beats/min (P light phase: wild type 484 +/- 13 vs. MCHR1(-/-) 539 +/- 9 beats/min (P vs. MCHR1(-/-) 113 +/- 0.4 mmHg (P > 0.05)]. Locomotor activity and core body temperature were higher in the MCHR1(-/-) mice during the dark phase only and thus temporally dissociated from heart rate differences. On fasting, wild-type animals rapidly downregulated body temperature and heart rate. MCHR1(-/-) mice displayed a distinct delay in the onset of this downregulation. To investigate the mechanism underlying these differences, autonomic blockade experiments were carried out. Administration of the adrenergic antagonist metoprolol completely reversed the tachycardia seen in MCHR1(-/-) mice, suggesting an increased sympathetic tone.

  1. Cortical visual impairment

    OpenAIRE

    Koželj, Urša

    2013-01-01

    In this thesis we discuss cortical visual impairment, diagnosis that is in the developed world in first place, since 20 percent of children with blindness or low vision are diagnosed with it. The objectives of the thesis are to define cortical visual impairment and the definition of characters suggestive of the cortical visual impairment as well as to search for causes that affect the growing diagnosis of cortical visual impairment. There are a lot of signs of cortical visual impairment. ...

  2. Patients with chronic tension-type headache demonstrate increased mechano-sensitivity of the supra-orbital nerve.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Coppieters, Michel W; Cuadrado, María Luz; Pareja, Juan A

    2008-04-01

    This study aimed to establish whether increased sensitivity to mechanical stimuli is present in neural tissues in chronic tension-type headache (CTTH). Muscle hyperalgesia is a common finding in CTTH. No previous studies have investigated the sensitivity of peripheral nerves in patients with CTTH. A blinded controlled study. Pressure pain thresholds (PPT) and pain intensity following palpation of the supra-orbital nerve (V1) were compared between 20 patients with CTTH and 20 healthy matched subjects. A pressure algometer and numerical pain rate scale were used to quantify PPT and pain to palpation. A headache diary was kept for 4 weeks to substantiate the diagnosis and record the pain history. The analysis of variance demonstrated significantly lower PPT for patients (0.86+/-0.13 kg/cm2) than controls (1.50+/-0.19 kg/cm2) (Por=0.72; P<.001). These findings reveal that mechanical hypersensitivity is not limited to muscles but also occurs in cranial nerves, and that the level of sensitization, either due to peripheral or central processes, is related to the severity of the primary headache.

  3. Increased cortical and deep grey matter sodium concentration is associated with physical and cognitive disability in relapse-onset multiple sclerosis

    DEFF Research Database (Denmark)

    Brownlee, WJ; Alves Da Mota, Patricia; Prados, Ferran

    digit modalities test (SDMT) and tests of verbal and visual memory. Linear regression was used to compare differences in tissue TSC between groups. Multivariable linear regression was used to identify independent associations between TSC and disability with adjustment for age, sex, disease duration......=0.40) and visual memory (β=-0.06, 95%CI -0.11, -.0.02, R2=0.19). Conclusion: Sodium accumulation in cortical and deep grey matter may reflect underlying neurodegeneration that is relevant to the development of long-term disability and cognitive impairment in relapse-onset MS. 23Na-MRI may become a secondary...

  4. Earthworms (Eisenia fetida) demonstrate potential for use in soil bioremediation by increasing the degradation rates of heavy crude oil hydrocarbons.

    Science.gov (United States)

    Martinkosky, Luke; Barkley, Jaimie; Sabadell, Gabriel; Gough, Heidi; Davidson, Seana

    2017-02-15

    Crude oil contamination widely impacts soil as a result of release during oil and gas exploration and production activities. The success of bioremediation methods to meet remediation goals often depends on the composition of the crude oil, the soil, and microbial community. Earthworms may enhance bioremediation by mixing and aerating the soil, and exposing soil microorganisms to conditions in the earthworm gut that lead to increased activity. In this study, the common composting earthworm Eisenia fetida was tested for utility to improve remediation of oil-impacted soil. E. fetida survival in soil contaminated with two distinct crude oils was tested in an artificial (lab-mixed) sandy loam soil, and survival compared to that in the clean soil. Crude oil with a high fraction of light-weight hydrocarbons was more toxic to earthworms than the crude oil with a high proportion of heavy polyaromatic and aliphatic hydrocarbons. The heavier crude oil was added to soil to create a 30,000mg/kg crude oil impacted soil, and degradation in the presence of added earthworms and feed, feed alone, or no additions was monitored over time and compared. Earthworm feed was spread on top to test effectiveness of no mixing. TPH degradation rate for the earthworm treatments was ~90mg/day slowing by 200days to ~20mg/day, producing two phases of degradation. With feed alone, the rate was ~40mg/day, with signs of slowing after 500days. Both treatments reached the same end point concentrations, and exhibited faster degradation of aliphatic hydrocarbons C21, decreased. During these experiments, soils were moderately toxic during the first three months, then earthworms survived well, were active and reproduced with petroleum hydrocarbons present. This study demonstrated that earthworms accelerate bioremediation of crude oil in soils, including the degradation of the heaviest polyaromatic fractions. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Where attention falls: Increased risk of falls from the converging impact of cortical cholinergic and midbrain dopamine loss on striatal function.

    Science.gov (United States)

    Sarter, Martin; Albin, Roger L; Kucinski, Aaron; Lustig, Cindy

    2014-07-01

    Falls are a major source of hospitalization, long-term institutionalization, and death in older adults and patients with Parkinson's disease (PD). Limited attentional resources are a major risk factor for falls. In this review, we specify cognitive-behavioral mechanisms that produce falls and map these mechanisms onto a model of multi-system degeneration. Results from PET studies in PD fallers and findings from a recently developed animal model support the hypothesis that falls result from interactions between loss of basal forebrain cholinergic projections to the cortex and striatal dopamine loss. Striatal dopamine loss produces inefficient, low-vigor gait, posture control, and movement. Cortical cholinergic deafferentation impairs a wide range of attentional processes, including monitoring of gait, posture and complex movements. Cholinergic cell loss reveals the full impact of striatal dopamine loss on motor performance, reflecting loss of compensatory attentional supervision of movement. Dysregulation of dorsomedial striatal circuitry is an essential, albeit not exclusive, mediator of falls in this dual-system model. Because cholinergic neuromodulatory activity influences cortical circuitry primarily via stimulation of α4β2* nicotinic acetylcholine receptors, and because agonists at these receptors are known to benefit attentional processes in animals and humans, treating PD fallers with such agonists, as an adjunct to dopaminergic treatment, is predicted to reduce falls. Falls are an informative behavioral endpoint to study attentional-motor integration by striatal circuitry. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Where attention falls: Increased risk of falls from the converging impact of cortical cholinergic and midbrain dopamine loss on striatal function

    Science.gov (United States)

    Sarter, Martin; Albin, Roger L.; Kucinski, Aaron; Lustig, Cindy

    2015-01-01

    Falls are a major source of hospitalization, long-term institutionalization, and death in older adults and patients with Parkinson’s disease (PD). Limited attentional resources are a major risk factor for falls. In this review, we specify cognitive–behavioral mechanisms that produce falls and map these mechanisms onto a model of multi-system degeneration. Results from PET studies in PD fallers and findings from a recently developed animal model support the hypothesis that falls result from interactions between loss of basal forebrain cholinergic projections to the cortex and striatal dopamine loss. Striatal dopamine loss produces inefficient, low-vigor gait, posture control, and movement. Cortical cholinergic deafferentation impairs a wide range of attentional processes, including monitoring of gait, posture and complex movements. Cholinergic cell loss reveals the full impact of striatal dopamine loss on motor performance, reflecting loss of compensatory attentional supervision of movement. Dysregulation of dorsomedial striatal circuitry is an essential, albeit not exclusive, mediator of falls in this dual-system model. Because cholinergic neuromodulatory activity influences cortical circuitry primarily via stimulation of α4β2* nicotinic acetylcholine receptors, and because agonists at these receptors are known to benefit attentional processes in animals and humans, treating PD fallers with such agonists, as an adjunct to dopaminergic treatment, is predicted to reduce falls. Falls are an informative behavioral endpoint to study attentional–motor integration by striatal circuitry. PMID:24805070

  7. Focal cortical dysplasia – review

    International Nuclear Information System (INIS)

    Kabat, Joanna; Król, Przemysław

    2012-01-01

    Focal cortical dysplasia is a malformation of cortical development, which is the most common cause of medically refractory epilepsy in the pediatric population and the second/third most common etiology of medically intractable seizures in adults. Both genetic and acquired factors are involved in the pathogenesis of cortical dysplasia. Numerous classifications of the complex structural abnormalities of focal cortical dysplasia have been proposed – from Taylor et al. in 1971 to the last modification of Palmini classification made by Blumcke in 2011. In general, three types of cortical dysplasia are recognized. Type I focal cortical dysplasia with mild symptomatic expression and late onset, is more often seen in adults, with changes present in the temporal lobe. Clinical symptoms are more severe in type II of cortical dysplasia usually seen in children. In this type, more extensive changes occur outside the temporal lobe with predilection for the frontal lobes. New type III is one of the above dysplasias with associated another principal lesion as hippocampal sclerosis, tumor, vascular malformation or acquired pathology during early life. Brain MRI imaging shows abnormalities in the majority of type II dysplasias and in only some of type I cortical dysplasias. The most common findings on MRI imaging include: focal cortical thickening or thinning, areas of focal brain atrophy, blurring of the gray-white junction, increased signal on T2- and FLAIR-weighted images in the gray and subcortical white matter often tapering toward the ventricle. On the basis of the MRI findings, it is possible to differentiate between type I and type II cortical dysplasia. A complete resection of the epileptogenic zone is required for seizure-free life. MRI imaging is very helpful to identify those patients who are likely to benefit from surgical treatment in a group of patients with drug-resistant epilepsy. However, in type I cortical dysplasia, MR imaging is often normal, and also in both

  8. Impact of prenatal environmental stress on cortical development

    Directory of Open Access Journals (Sweden)

    Seiji eIshii

    2015-05-01

    Full Text Available Prenatal exposure of the developing brain to various types of environmental stress increases susceptibility to neuropsychiatric disorders such as autism, attention deficit hyperactivity disorder and schizophrenia. Given that even subtle perturbations by prenatal environmental stress in the cerebral cortex impair the cognitive and memory functions, this review focuses on underlying molecular mechanisms of pathological cortical development. We especially highlight recent works that utilized animal exposure models, human specimens or/and induced Pluripotent Stem (iPS cells to demonstrate: 1. molecular mechanisms shared by various types of environmental stressors, 2. the mechanisms by which the affected extracortical tissues indirectly impact the cortical development and function, and 3. interaction between prenatal environmental stress and the genetic predisposition of neuropsychiatric disorders. Finally, we discuss current challenges for achieving a comprehensive understanding of the role of environmentally disturbed molecular expressions in cortical maldevelopment, knowledge of which may eventually facilitate discovery of interventions for prenatal environment-linked neuropsychiatric disorders.

  9. Chronic Underactivity of Medial Frontal Cortical β2-Containing Nicotinic Receptors Increases Clozapine-Induced Working Memory Impairment in Female Rats

    Science.gov (United States)

    Levin, Edward D.; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N. Channelle

    2009-01-01

    Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of β2-containing nicotinic receptors with dihydro-β-erythrodine (DHβE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal α7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical α7 and β2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHβE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHβE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHβE infusion potentiated clozapine-induced memory impairment, whereas previously the memory

  10. Chronic underactivity of medial frontal cortical beta2-containing nicotinic receptors increases clozapine-induced working memory impairment in female rats.

    Science.gov (United States)

    Levin, Edward D; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N Channelle

    2009-03-17

    Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of beta2-containing nicotinic receptors with dihydro-beta-erythrodine (DHbetaE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal alpha7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical alpha7 and beta2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHbetaE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHbetaE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHbetaE infusion potentiated clozapine-induced memory impairment, whereas previously

  11. Increased cortical and deep grey matter sodium concentration is associated with physical and cognitive disability in relapse-onset multiple sclerosis

    DEFF Research Database (Denmark)

    Brownlee, WJ; Alves Da Mota, Patricia; Prados, Ferran

    digit modalities test (SDMT) and tests of verbal and visual memory. Linear regression was used to compare differences in tissue TSC between groups. Multivariable linear regression was used to identify independent associations between TSC and disability with adjustment for age, sex, disease duration......=0.40) and visual memory (β=-0.06, 95%CI -0.11, -.0.02, R2=0.19). Conclusion: Sodium accumulation in cortical and deep grey matter may reflect underlying neurodegeneration that is relevant to the development of long-term disability and cognitive impairment in relapse-onset MS. 23Na-MRI may become a secondary......-appearing white matter (NAWM), T1-isointense and T1-hypointense lesions was calculated. Physical disability was assessed using the Expanded Disability Status Scale (EDSS), timed 25-foot walk test (TWT) and 9-hole peg test (9HPT). Cognition was assessed using the paced auditory serial addition test (PASAT), symbol...

  12. Differential Reinforcement of Alternative Behavior Increases Resistance to Extinction: Clinical Demonstration, Animal Modeling, and Clinical Test of One Solution

    Science.gov (United States)

    Mace, F. Charles; McComas, Jennifer J.; Mauro, Benjamin C.; Progar, Patrick R.; Taylor, Bridget; Ervin, Ruth; Zangrillo, Amanda N.

    2010-01-01

    Basic research with pigeons on behavioral momentum suggests that differential reinforcement of alternative behavior (DRA) can increase the resistance of target behavior to change. This finding suggests that clinical applications of DRA may inadvertently increase the persistence of target behavior even as it decreases its frequency. We conducted…

  13. Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine.

    Science.gov (United States)

    Leke, Renata; Bak, Lasse K; Anker, Malene; Melø, Torun M; Sørensen, Michael; Keiding, Susanne; Vilstrup, Hendrik; Ott, Peter; Portela, Luis V; Sonnewald, Ursula; Schousboe, Arne; Waagepetersen, Helle S

    2011-04-01

    Cerebral hyperammonemia is believed to play a pivotal role in the development of hepatic encephalopathy (HE), a debilitating condition arising due to acute or chronic liver disease. In the brain, ammonia is thought to be detoxified via the activity of glutamine synthetase, an astrocytic enzyme. Moreover, it has been suggested that cerebral tricarboxylic acid (TCA) cycle metabolism is inhibited and glycolysis enhanced during hyperammonemia. The aim of this study was to characterize the ammonia-detoxifying mechanisms as well as the effects of ammonia on energy-generating metabolic pathways in a mouse neuronal-astrocytic co-culture model of the GABAergic system. We found that 5 mM ammonium chloride affected energy metabolism by increasing the neuronal TCA cycle activity and switching the astrocytic TCA cycle toward synthesis of substrate for glutamine synthesis. Furthermore, ammonia exposure enhanced the synthesis and release of alanine. Collectively, our results demonstrate that (1) formation of glutamine is seminal for detoxification of ammonia; (2) neuronal oxidative metabolism is increased in the presence of ammonia; and (3) synthesis and release of alanine is likely to be important for ammonia detoxification as a supplement to formation of glutamine.

  14. Localization of cortical areas activated by thinking.

    Science.gov (United States)

    Roland, P E; Friberg, L

    1985-05-01

    These experiments were undertaken to demonstrate that pure mental activity, thinking, increases the cerebral blood flow and that different types of thinking increase the regional cerebral blood flow (rCBF) in different cortical areas. As a first approach, thinking was defined as brain work in the form of operations on internal information, done by an awake subject. The rCBF was measured in 254 cortical regions in 11 subjects with the intracarotid 133Xe injection technique. In normal man, changes in the regional cortical metabolic rate of O2 leads to proportional changes in rCBF. One control study was taken with the subjects at rest. Then the rCBF was measured during three different simple algorithm tasks, each consisting of retrieval of a specific memory followed by a simple operation on the retrieved information. Once started, the information processing went on in the brain without any communication with the outside world. In 50-3 thinking, the subjects started with 50 and then, in their minds only, continuously subtracted 3 from the result. In jingle thinking the subjects internally jumped every second word in a nine-word circular jingle. In route-finding thinking the subjects imagined that they started at their front door and then walked alternatively to the left or the right each time they reached a corner. The rCBF increased only in homotypical cortical areas during thinking. The areas in the superior prefrontal cortex increased their rCBF equivalently during the three types of thinking. In the remaining parts of the prefrontal cortex there were multifocal increases of rCBF. The localizations and intensities of these rCBF increases depended on the type of internal operation occurring. The rCBF increased bilaterally in the angular cortex during 50-3 thinking. The rCBF increased in the right midtemporal cortex exclusively during jingle thinking. The intermediate and remote visual association areas, the superior occipital, posterior inferior temporal, and

  15. Visual and Motor Recovery After "Cognitive Therapeutic Exercises" in Cortical Blindness: A Case Study.

    Science.gov (United States)

    De Patre, Daniele; Van de Winckel, Ann; Panté, Franca; Rizzello, Carla; Zernitz, Marina; Mansour, Mariam; Zordan, Lara; Zeffiro, Thomas A; OʼConnor, Erin E; Bisson, Teresa; Lupi, Andrea; Perfetti, Carlo

    2017-07-01

    Spontaneous visual recovery is rare after cortical blindness. While visual rehabilitation may improve performance, no visual therapy has been widely adopted, as clinical outcomes are variable and rarely translate into improvements in activities of daily living (ADLs). We explored the potential value of a novel rehabilitation approach "cognitive therapeutic exercises" for cortical blindness. The subject of this case study was 48-year-old woman with cortical blindness and tetraplegia after cardiac arrest. Prior to the intervention, she was dependent in ADLs and poorly distinguished shapes and colors after 19 months of standard visual and motor rehabilitation. Computed tomographic images soon after symptom onset demonstrated acute infarcts in both occipital cortices. The subject underwent 8 months of intensive rehabilitation with "cognitive therapeutic exercises" consisting of discrimination exercises correlating sensory and visual information. Visual fields increased; object recognition improved; it became possible to watch television; voluntary arm movements improved in accuracy and smoothness; walking improved; and ADL independence and self-reliance increased. Subtraction of neuroimaging acquired before and after rehabilitation showed that focal glucose metabolism increases bilaterally in the occipital poles. This study demonstrates feasibility of "cognitive therapeutic exercises" in an individual with cortical blindness, who experienced impressive visual and sensorimotor recovery, with marked ADL improvement, more than 2 years after ischemic cortical damage.Video Abstract available for additional insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A173).

  16. Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis.

    Science.gov (United States)

    Villanova, Federica; Flutter, Barry; Tosi, Isabella; Grys, Katarzyna; Sreeneebus, Hemawtee; Perera, Gayathri K; Chapman, Anna; Smith, Catherine H; Di Meglio, Paola; Nestle, Frank O

    2014-04-01

    Innate lymphoid cells (ILCs) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterize the ILCs in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in the skin and blood of normal individuals and psoriasis patients are CD3-negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in the blood of psoriasis patients compared with healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte-associated antigen, indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILCs in the skin compared with blood. Moreover, the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared with normal skin. A detailed time course of a psoriasis patient treated with anti-tumor necrosis factor showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis.

  17. Characterization of innate lymphoid cells (ILC) in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis

    Science.gov (United States)

    Tosi, Isabella; Grys, Katarzyna; Sreeneebus, Hemawtee; Perera, Gayathri K; Chapman, Anna; Smith, Catherine H; Di Meglio, Paola; Nestle, Frank O

    2013-01-01

    Innate lymphoid cells (ILC) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterise the ILC in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in skin and blood of normal individuals and psoriasis patients are CD3 negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in blood of psoriasis patients compared to healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte-associated antigen indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILC in skin compared to blood. Moreover the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared to normal skin. A detailed time course of a psoriasis patient treated with anti-TNF showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis. PMID:24352038

  18. Increasing resiliency to natural hazards - A strategic plan for the Multi-Hazards Demonstration Project in Southern California

    Science.gov (United States)

    Jones, Lucy; Bernknopf, Richard; Cannon, Susan; Cox, Dale A.; Gaydos, Len; Keeley, Jon; Kohler, Monica; Lee, Homa; Ponti, Daniel; Ross, Stephanie L.; Schwarzbach, Steven; Shulters, Michael; Ward, A. Wesley; Wein, Anne

    2007-01-01

    The U.S. Geological Survey (USGS) is initiating a new project designed to improve resiliency to natural hazards in southern California through the application of science to community decision making and emergency response. The Multi-Hazards Demonstration Project will assist the region’s communities to reduce their risk from natural hazards by directing new and existing research towards the community’s needs, improving monitoring technology, producing innovative products, and improving dissemination of the results. The natural hazards to be investigated in this project include coastal erosion, earthquakes, floods, landslides, tsunamis, and wildfires.Americans are more at risk from natural hazards now than at any other time in our Nation’s history. Southern California, in particular, has one of the Nation’s highest potentials for extreme catastrophic losses due to natural hazards, with estimates of expected losses exceeding $3 billion per year. These losses can only be reduced through the decisions of the southern California community itself. To be effective, these decisions must be guided by the best information about hazards, risk, and the cost-effectiveness of mitigation technologies. The USGS will work with collaborators to set the direction of the research and to create multi-hazard risk frameworks where communities can apply the results of scientific research to their decision-making processes. Partners include state, county, city, and public-lands government agencies, public and private utilities, companies with a significant impact and presence in southern California, academic researchers, the Federal Emergency Management Agency (FEMA), National Oceanic and Atmospheric Administration (NOAA), and local emergency response agencies.Prior to the writing of this strategic plan document, three strategic planning workshops were held in February and March 2006 at the USGS office in Pasadena to explore potential relationships. The goal of these planning

  19. Is cortical bone hip? What determines cortical bone properties?

    Science.gov (United States)

    Epstein, Sol

    2007-07-01

    Increased bone turnover may produce a disturbance in bone structure which may result in fracture. In cortical bone, both reduction in turnover and increase in hip bone mineral density (BMD) may be necessary to decrease hip fracture risk and may require relatively greater proportionate changes than for trabecular bone. It should also be noted that increased porosity produces disproportionate reduction in bone strength, and studies have shown that increased cortical porosity and decreased cortical thickness are associated with hip fracture. Continued studies for determining the causes of bone strength and deterioration show distinct promise. Osteocyte viability has been observed to be an indicator of bone strength, with viability as the result of maintaining physiological levels of loading and osteocyte apoptosis as the result of a decrease in loading. Osteocyte apoptosis and decrease are major factors in the bone loss and fracture associated with aging. Both the osteocyte and periosteal cell layer are assuming greater importance in the process of maintaining skeletal integrity as our knowledge of these cells expand, as well being a target for pharmacological agents to reduce fracture especially in cortical bone. The bisphosphonate alendronate has been seen to have a positive effect on cortical bone by allowing customary periosteal growth, while reducing the rate of endocortical bone remodeling and slowing bone loss from the endocortical surface. Risedronate treatment effects were attributed to decrease in bone resorption and thus a decrease in fracture risk. Ibandronate has been seen to increase BMD as the spine and femur as well as a reduced incidence of new vertebral fractures and non vertebral on subset post hoc analysis. And treatment with the anabolic agent PTH(1-34) documented modeling and remodelling of quiescent and active bone surfaces. Receptor activator of nuclear factor kappa B ligand (RANKL) plays a key role in bone destruction, and the human monoclonal

  20. 5-(2-Aminopropyl)benzofuran and phenazepam demonstrate the possibility of dependence by increasing dopamine levels in the brain.

    Science.gov (United States)

    Cha, Hye Jin; Lee, Kwang-Wook; Eom, Jang-Hyeon; Kim, Young-Hoon; Shin, Jisoon; Yun, Jaesuk; Han, Kyoungmoon; Kim, Hyung Soo

    2016-10-01

    Although 5-(2-aminopropyl)benzofuran (5-APB) and 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (phenazepam) are being used as recreational drugs, research on their dependence liability or mechanisms of action is lacking. The present study aimed to evaluate the behavioral effects and dependence liability of these drugs using conditioned place preference and self-administration paradigms in rodents. Additionally, biochemical techniques were used to assess the substance-induced alterations in synaptosome-released dopamine. While both of the tested substances elicited increases in conditioned place preference and dopamine, neither of them facilitated self-administration, suggesting that 5-APB and phenazepam have rewarding effects, rather than reinforcing effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.

    Science.gov (United States)

    Mardinly, A R; Spiegel, I; Patrizi, A; Centofante, E; Bazinet, J E; Tzeng, C P; Mandel-Brehm, C; Harmin, D A; Adesnik, H; Fagiolini, M; Greenberg, M E

    2016-03-17

    Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.

  2. Curved reformat of the paediatric brain MRI into a 'flat-earth map' - standardised method for demonstrating cortical surface atrophy resulting from hypoxic-ischaemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, Ewan [Bristol Royal Hospital for Children, Department of Pediatric Radiology, Bristol (United Kingdom); Andronikou, Savvas [Bristol Royal Hospital for Children, Department of Pediatric Radiology, Bristol (United Kingdom); University of Bristol, CRICBristol, Bristol (United Kingdom); Vedajallam, Schadie; Chacko, Anith; Thai, Ngoc Jade [University of Bristol, CRICBristol, Bristol (United Kingdom)

    2016-09-15

    Hypoxic-ischaemic encephalopathy is optimally imaged with brain MRI in the neonatal period. However neuroimaging is often also performed later in childhood (e.g., when parents seek compensation in cases of alleged birth asphyxia). We describe a standardised technique for creating two curved reconstructions of the cortical surface to show the characteristic surface changes of hypoxic-ischaemic encephalopathy in children imaged after the neonatal period. The technique was applied for 10 cases of hypoxic-ischaemic encephalopathy and also for age-matched healthy children to assess the visibility of characteristic features of hypoxic-ischaemic encephalopathy. In the abnormal brains, fissural or sulcal widening was seen in all cases and ulegyria was identifiable in 7/10. These images could be used as a visual aid for communicating MRI findings to clinicians and other interested parties. (orig.)

  3. Curved reformat of the paediatric brain MRI into a 'flat-earth map' - standardised method for demonstrating cortical surface atrophy resulting from hypoxic-ischaemic encephalopathy

    International Nuclear Information System (INIS)

    Simpson, Ewan; Andronikou, Savvas; Vedajallam, Schadie; Chacko, Anith; Thai, Ngoc Jade

    2016-01-01

    Hypoxic-ischaemic encephalopathy is optimally imaged with brain MRI in the neonatal period. However neuroimaging is often also performed later in childhood (e.g., when parents seek compensation in cases of alleged birth asphyxia). We describe a standardised technique for creating two curved reconstructions of the cortical surface to show the characteristic surface changes of hypoxic-ischaemic encephalopathy in children imaged after the neonatal period. The technique was applied for 10 cases of hypoxic-ischaemic encephalopathy and also for age-matched healthy children to assess the visibility of characteristic features of hypoxic-ischaemic encephalopathy. In the abnormal brains, fissural or sulcal widening was seen in all cases and ulegyria was identifiable in 7/10. These images could be used as a visual aid for communicating MRI findings to clinicians and other interested parties. (orig.)

  4. Reye's syndrome with cortical laminar necrosis: MRI

    International Nuclear Information System (INIS)

    Kinoshita, T.; Takahashi, S.; Ishii, K.; Higano, S.; Matsumoto, K.; Sakamoto, K.; Haginoya, K.; Iinuma, K.

    1996-01-01

    Serial MRI findings are described in two patients with Reye's syndrome, demonstrating diffuse cortical and white matter changes. In the acute stage, T2-weighted images showed subtle but definite laminar high signal and contrast-enhanced T1-weighted images laminar enhancement, along the entire cerebral cortex bilaterally. In the chronic stage, unenhanced T1-weighted images showed diffuse cortical laminar high signal. These characteristic MRI features seemed very similar to those of laminar cortical necrosis in hypoxic brain damage. MRI also displayed delayed white matter changes with cerebral atrophy. (orig.)

  5. Reliability and statistical power analysis of cortical and subcortical FreeSurfer metrics in a large sample of healthy elderly.

    Science.gov (United States)

    Liem, Franziskus; Mérillat, Susan; Bezzola, Ladina; Hirsiger, Sarah; Philipp, Michel; Madhyastha, Tara; Jäncke, Lutz

    2015-03-01

    FreeSurfer is a tool to quantify cortical and subcortical brain anatomy automatically and noninvasively. Previous studies have reported reliability and statistical power analyses in relatively small samples or only selected one aspect of brain anatomy. Here, we investigated reliability and statistical power of cortical thickness, surface area, volume, and the volume of subcortical structures in a large sample (N=189) of healthy elderly subjects (64+ years). Reliability (intraclass correlation coefficient) of cortical and subcortical parameters is generally high (cortical: ICCs>0.87, subcortical: ICCs>0.95). Surface-based smoothing increases reliability of cortical thickness maps, while it decreases reliability of cortical surface area and volume. Nevertheless, statistical power of all measures benefits from smoothing. When aiming to detect a 10% difference between groups, the number of subjects required to test effects with sufficient power over the entire cortex varies between cortical measures (cortical thickness: N=39, surface area: N=21, volume: N=81; 10mm smoothing, power=0.8, α=0.05). For subcortical regions this number is between 16 and 76 subjects, depending on the region. We also demonstrate the advantage of within-subject designs over between-subject designs. Furthermore, we publicly provide a tool that allows researchers to perform a priori power analysis and sensitivity analysis to help evaluate previously published studies and to design future studies with sufficient statistical power. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Agonist contraction during intermittent theta burst stimulation enhances motor cortical plasticity of the wrist flexors.

    Science.gov (United States)

    Mirdamadi, J L; Suzuki, L Y; Meehan, S K

    2015-03-30

    Differences in cortical control across the different muscles of the upper limb may mitigate the efficacy of TMS interventions targeting a specific muscle. The current study sought to determine whether weak concurrent contraction during TMS could enhance the efficacy of intermittent theta burst stimulation (iTBS) in the forearm flexors. Motor evoked potentials (MEP) were elicited from the flexor (FCR) and extensor carpi radialis (ECR) motor cortical hotspots before and after iTBS over the FCR cortical hotspot. During iTBS the FCR was either relaxed (iTBS-Relax) or tonically contracted to 10% of maximum voluntary force (iTBS-Contract). iTBS-Relax failed to produce consistent potentiation of MEPFCR amplitude. Individuals with a relatively lower RMTFCR compared RMTECR demonstrated MEPFCR facilitation post-iTBS-Relax. Individuals with relatively higher RMTFCR demonstrated less facilitation and even suppression of MEPFCR amplitude. iTBS-Contract facilitated MEPFCR amplitude but only for MEPFCR evoked from the ECR hotspot. Interactions between overlapping cortical representations determine the efficacy of iTBS. Tonic contraction increases the efficacy of iTBS by enhancing the volume of the cortical representation. However, metaplastic effects may attenuate the enhancement of MEP gain at the motor cortical hotspot. The use of TMS as an adjunct to physical therapy should account for inter-muscle interactions when targeting muscles of the forearm. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Localization of cortical areas activated by thinking

    DEFF Research Database (Denmark)

    Roland, P E; Friberg, L

    1985-01-01

    midtemporal cortex exclusively during jingle thinking. The intermediate and remote visual association areas, the superior occipital, posterior inferior temporal, and posterior superior parietal cortex, increased their rCBF exclusively during route-finding thinking. We observed no decreases in rCBF. All r......These experiments were undertaken to demonstrate that pure mental activity, thinking, increases the cerebral blood flow and that different types of thinking increase the regional cerebral blood flow (rCBF) in different cortical areas. As a first approach, thinking was defined as brain work...... communication with the outside world. In 50-3 thinking, the subjects started with 50 and then, in their minds only, continuously subtracted 3 from the result. In jingle thinking the subjects internally jumped every second word in a nine-word circular jingle. In route-finding thinking the subjects imagined...

  8. Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease.

    Science.gov (United States)

    Udupa, Kaviraja; Bahl, Nina; Ni, Zhen; Gunraj, Carolyn; Mazzella, Filomena; Moro, Elena; Hodaie, Mojgan; Lozano, Andres M; Lang, Anthony E; Chen, Robert

    2016-01-13

    -DBS with TMS at short (∼ 3 ms) and medium (∼ 23 ms) intervals increased cortical excitability that lasted for up to 45 min, whereas the control condition (fixed latency of 167 ms) had no effects on cortical excitability. This is the first demonstration of associative plasticity in the STN-M1 circuits in PD patients using this novel technique. The potential therapeutic effects of combining DBS and noninvasive cortical stimulation should be investigated further. Copyright © 2016 the authors 0270-6474/16/360397-09$15.00/0.

  9. Scaling Up Cortical Control Inhibits Pain

    Directory of Open Access Journals (Sweden)

    Jahrane Dale

    2018-05-01

    Full Text Available Summary: Acute pain evokes protective neural and behavioral responses. Chronic pain, however, disrupts normal nociceptive processing. The prefrontal cortex (PFC is known to exert top-down regulation of sensory inputs; unfortunately, how individual PFC neurons respond to an acute pain signal is not well characterized. We found that neurons in the prelimbic region of the PFC increased firing rates of the neurons after noxious stimulations in free-moving rats. Chronic pain, however, suppressed both basal spontaneous and pain-evoked firing rates. Furthermore, we identified a linear correlation between basal and evoked firing rates of PFC neurons, whereby a decrease in basal firing leads to a nearly 2-fold reduction in pain-evoked response in chronic pain states. In contrast, enhancing basal PFC activity with low-frequency optogenetic stimulation scaled up prefrontal outputs to inhibit pain. These results demonstrate a cortical gain control system for nociceptive regulation and establish scaling up prefrontal outputs as an effective neuromodulation strategy to inhibit pain. : Dale et al. find that acute pain increases activity levels in the prefrontal cortex. Chronic pain reduces both basal spontaneous and pain-evoked activity in this region, whereas neurostimulation to restore basal activities can in turn enhance nociception-evoked prefrontal activities to inhibit pain. Keywords: chronic pain, neuromodulation, prefrontal cortex, PFC, cortical gain control

  10. Discrimination of cortical laminae using MEG.

    Science.gov (United States)

    Troebinger, Luzia; López, José David; Lutti, Antoine; Bestmann, Sven; Barnes, Gareth

    2014-11-15

    Typically MEG source reconstruction is used to estimate the distribution of current flow on a single anatomically derived cortical surface model. In this study we use two such models representing superficial and deep cortical laminae. We establish how well we can discriminate between these two different cortical layer models based on the same MEG data in the presence of different levels of co-registration noise, Signal-to-Noise Ratio (SNR) and cortical patch size. We demonstrate that it is possible to make a distinction between superficial and deep cortical laminae for levels of co-registration noise of less than 2mm translation and 2° rotation at SNR > 11 dB. We also show that an incorrect estimate of cortical patch size will tend to bias layer estimates. We then use a 3D printed head-cast (Troebinger et al., 2014) to achieve comparable levels of co-registration noise, in an auditory evoked response paradigm, and show that it is possible to discriminate between these cortical layer models in real data. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Imprinting and recalling cortical ensembles.

    Science.gov (United States)

    Carrillo-Reid, Luis; Yang, Weijian; Bando, Yuki; Peterka, Darcy S; Yuste, Rafael

    2016-08-12

    Neuronal ensembles are coactive groups of neurons that may represent building blocks of cortical circuits. These ensembles could be formed by Hebbian plasticity, whereby synapses between coactive neurons are strengthened. Here we report that repetitive activation with two-photon optogenetics of neuronal populations from ensembles in the visual cortex of awake mice builds neuronal ensembles that recur spontaneously after being imprinted and do not disrupt preexisting ones. Moreover, imprinted ensembles can be recalled by single- cell stimulation and remain coactive on consecutive days. Our results demonstrate the persistent reconfiguration of cortical circuits by two-photon optogenetics into neuronal ensembles that can perform pattern completion. Copyright © 2016, American Association for the Advancement of Science.

  12. Effects of parietal TMS on visual and auditory processing at the primary cortical level -- a concurrent TMS-fMRI study

    DEFF Research Database (Denmark)

    Leitão, Joana; Thielscher, Axel; Werner, Sebastian

    2013-01-01

    cortices under 3 sensory contexts: visual, auditory, and no stimulation. IPS-TMS increased activations in auditory cortices irrespective of sensory context as a result of direct and nonspecific auditory TMS side effects. In contrast, IPS-TMS modulated activations in the visual cortex in a state...... deactivations induced by auditory activity to TMS sounds. TMS to IPS may increase the responses in visual (or auditory) cortices to visual (or auditory) stimulation via a gain control mechanism or crossmodal interactions. Collectively, our results demonstrate that understanding TMS effects on (uni......Accumulating evidence suggests that multisensory interactions emerge already at the primary cortical level. Specifically, auditory inputs were shown to suppress activations in visual cortices when presented alone but amplify the blood oxygen level-dependent (BOLD) responses to concurrent visual...

  13. Comparing the influence of crestal cortical bone and sinus floor cortical bone in posterior maxilla bi-cortical dental implantation: a three-dimensional finite element analysis.

    Science.gov (United States)

    Yan, Xu; Zhang, Xinwen; Chi, Weichao; Ai, Hongjun; Wu, Lin

    2015-05-01

    This study aimed to compare the influence of alveolar ridge cortical bone and sinus floor cortical bone in sinus areabi-cortical dental implantation by means of 3D finite element analysis. Three-dimensional finite element (FE) models in a posterior maxillary region with sinus membrane and the same height of alveolar ridge of 10 mm were generated according to the anatomical data of the sinus area. They were either with fixed thickness of crestal cortical bone and variable thickness of sinus floor cortical bone or vice versa. Ten models were assumed to be under immediate loading or conventional loading. The standard implant model based on the Nobel Biocare implant system was created via computer-aided design software. All materials were assumed to be isotropic and linearly elastic. An inclined force of 129 N was applied. Von Mises stress mainly concentrated on the surface of crestal cortical bone around the implant neck. For all the models, both the axial and buccolingual resonance frequencies of conventional loading were higher than those of immediate loading; however, the difference is less than 5%. The results showed that bi-cortical implant in sinus area increased the stability of the implant, especially for immediately loading implantation. The thickness of both crestal cortical bone and sinus floor cortical bone influenced implant micromotion and stress distribution; however, crestal cortical bone may be more important than sinus floor cortical bone.

  14. Six months of disuse during hibernation does not increase intracortical porosity or decrease cortical bone geometry, strength, or mineralization in black bear (Ursus americanus) femurs

    OpenAIRE

    McGee-Lawrence, Meghan E.; Wojda, Samantha J.; Barlow, Lindsay N.; Drummer, Thomas D.; Bunnell, Kevin; Auger, Janene; Black, Hal L.; Donahue, Seth W.

    2009-01-01

    Disuse typically uncouples bone formation from resorption, leading to bone loss which compromises bone mechanical properties and increases the risk of bone fracture. Previous studies suggest that bears can prevent bone loss during long periods of disuse (hibernation), but small sample sizes have limited the conclusions that can be drawn regarding the effects of hibernation on bone structure and strength in bears. Here we quantified the effects of hibernation on structural, mineral, and mechan...

  15. Cortical bone metastases

    International Nuclear Information System (INIS)

    Davis, T.M. Jr.; Rogers, L.F.; Hendrix, R.W.

    1986-01-01

    Twenty-five cases of bone metastases involving the cortex alone are reviewed. Seven patients had primary lung carcinoma, while 18 had primary tumors not previously reported to produce cortical bone metastases (tumors of the breast, kidney, pancreas, adenocarcinoma of unknown origin, multiple myeloma). Radiographically, these cortical lesions were well circumscribed, osteolytic, and produced soft-tissue swelling and occasional periosteal reaction. A recurrent pattern of metadiaphyseal involvement of the long bones of the lower extremity (particularly the femur) was noted, and is discussed. Findings reported in the literature, review, pathophysiology, and the role of skeletal radiographs, bone scans, and CT scans in evaluating cortical bone metastases are addressed

  16. Does aging with a cortical lesion increase fall-risk: Examining effect of age versus stroke on intensity modulation of reactive balance responses from slip-like perturbations.

    Science.gov (United States)

    Patel, Prakruti J; Bhatt, Tanvi

    2016-10-01

    We examined whether aging with and without a cerebral lesion such as stroke affects modulation of reactive balance response for recovery from increasing intensity of sudden slip-like stance perturbations. Ten young adults, older age-match adults and older chronic stroke survivors were exposed to three different levels of slip-like perturbations, level 1 (7.75m/s(2)), Level II (12.00m/s(2)) and level III (16.75m/s(2)) in stance. The center of mass (COM) state stability was computed as the shortest distance of the instantaneous COM position and velocity relative to base of support (BOS) from a theoretical threshold for backward loss of balance (BLOB). The COM position (XCOM/BOS) and velocity (ẊCOM/BOS) relative to BOS at compensatory step touchdown, compensatory step length and trunk angle at touchdown were also recorded. At liftoff, stability reduced with increasing perturbation intensity across all groups (main effect of intensity pbalance control, potentially contributing toward a higher fall risk in older stroke survivors. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Decreased prefrontal cortical dopamine transmission in alcoholism.

    Science.gov (United States)

    Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

    2014-08-01

    Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

  18. Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine

    DEFF Research Database (Denmark)

    Leke, Renata; Bak, Lasse Kristoffer; Anker, Malene

    2011-01-01

    Cerebral hyperammonemia is believed to play a pivotal role in the development of hepatic encephalopathy (HE), a debilitating condition arising due to acute or chronic liver disease. In the brain, ammonia is thought to be detoxified via the activity of glutamine synthetase, an astrocytic enzyme....... Moreover, it has been suggested that cerebral tricarboxylic acid (TCA) cycle metabolism is inhibited and glycolysis enhanced during hyperammonemia. The aim of this study was to characterize the ammonia-detoxifying mechanisms as well as the effects of ammonia on energy-generating metabolic pathways...... in a mouse neuronal-astrocytic co-culture model of the GABAergic system. We found that 5 mM ammonium chloride affected energy metabolism by increasing the neuronal TCA cycle activity and switching the astrocytic TCA cycle toward synthesis of substrate for glutamine synthesis. Furthermore, ammonia exposure...

  19. PROGESTERONE INCREASES BDNF EXPRESSION AND PROTECTS AGAINST GLUTAMATE TOXICITY IN A MAPK- AND PI3-K - DEPENDENT MANNER IN CEREBRAL CORTICAL EXPLANTS

    Science.gov (United States)

    Kaur, Paramjit; Jodhka, Parmeet K.; Underwood, Wendy A.; Bowles, Courtney A.; de Fiebre, NancyEllen C.; de Fiebre, Christopher M.; Singh, Meharvan

    2009-01-01

    The higher prevalence and risk for Alzheimer’s disease in women relative to men has been partially attributed to the precipitous decline in gonadal hormone levels that occur in women following the menopause. While considerable attention has focused on the consequence of estrogen loss, and thus, estrogen’s neuroprotective potential, it is important to recognize that the menopause results in a precipitous decline in progesterone levels as well. In fact, progesterone is neuroprotective, although the precise mechanisms involved remain unclear. Based on our previous observation that progesterone elicits the phosphorylation of ERK and Akt, key effectors of the neuroprotective MAPK and PI3-K pathways, respectively, we determined if activation of either of these pathways was necessary for progesterone-induced protection. Using organotypic explants (slice culture) of the cerebral cortex, we found that progesterone protected against glutamate-induced toxicity. Further, these protective effects were inhibited by either the MEK1/2 inhibitor, UO126, or the PI-3K inhibitor, LY294002, supporting the requirement of both the MAPK and PI-3K pathways in progesterone-induced protection. In addition, at a concentration and duration of treatment consistent with our neuroprotection data, progesterone also increased the expression of Brain-Derived Neurotrophic Factor (BDNF), at the level of both protein and mRNA. This induction of BDNF may be relevant to the protective effects of progesterone since inhibition of Trk signaling, using K252a, inhibited the protective effects of progesterone. Collectively, these data suggest that progesterone is protective via multiple and potentially related mechanisms. PMID:17549730

  20. Increased expression of matrix extracellular phosphoglycoprotein (MEPE in cortical bone of the rat tibia after mechanical loading: identification by oligonucleotide microarray.

    Directory of Open Access Journals (Sweden)

    Christianne M A Reijnders

    Full Text Available Skeletal integrity in humans and animals is maintained by daily mechanical loading. It has been widely accepted that osteocytes function as mechanosensors. Many biochemical signaling molecules are involved in the response of osteocytes to mechanical stimulation. The aim of this study was to identify genes involved in the translation of mechanical stimuli into bone formation. The four-point bending model was used to induce a single period of mechanical loading on the right tibia, while the contra lateral left tibia served as control. Six hours after loading, the effects of mechanical loading on gene-expression were determined with microarray analysis. Protein expression of differentially regulated genes was evaluated with immunohistochemistry. Nine genes were found to exhibit a significant differential gene expression in LOAD compared to control. MEPE, Garnl1, V2R2B, and QFG-TN1 olfactory receptor were up-regulated, and creatine kinase (muscle form, fibrinogen-B beta-polypeptide, monoamine oxidase A, troponin-C and kinesin light chain-C were down-regulated. Validation with real-time RT-PCR analysis confirmed the up-regulation of MEPE and the down-regulation of creatine kinase (muscle form and troponin-C in the loaded tibia. Immunohistochemistry showed that the increase of MEPE protein expression was already detectable six hours after mechanical loading. In conclusion, these genes probably play a role during translation of mechanical stimuli six hours after mechanical loading. The modulation of MEPE expression may indicate a connection between bone mineralization and bone formation after mechanical stimulation.

  1. Rab3A, a possible marker of cortical granules, participates in cortical granule exocytosis in mouse eggs

    Energy Technology Data Exchange (ETDEWEB)

    Bello, Oscar Daniel; Cappa, Andrea Isabel; Paola, Matilde de; Zanetti, María Natalia [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Fukuda, Mitsunori [Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578 (Japan); Fissore, Rafael A. [Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, 661 North Pleasant Street, Amherst, MA 01003 (United States); Mayorga, Luis S. [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Michaut, Marcela A., E-mail: mmichaut@gmail.com [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo (Argentina)

    2016-09-10

    Fusion of cortical granules with the oocyte plasma membrane is the most significant event to prevent polyspermy. This particular exocytosis, also known as cortical reaction, is regulated by calcium and its molecular mechanism is still not known. Rab3A, a member of the small GTP-binding protein superfamily, has been implicated in calcium-dependent exocytosis and is not yet clear whether Rab3A participates in cortical granules exocytosis. Here, we examine the involvement of Rab3A in the physiology of cortical granules, particularly, in their distribution during oocyte maturation and activation, and their participation in membrane fusion during cortical granule exocytosis. Immunofluorescence and Western blot analysis showed that Rab3A and cortical granules have a similar migration pattern during oocyte maturation, and that Rab3A is no longer detected after cortical granule exocytosis. These results suggested that Rab3A might be a marker of cortical granules. Overexpression of EGFP-Rab3A colocalized with cortical granules with a Pearson correlation coefficient of +0.967, indicating that Rab3A and cortical granules have almost a perfect colocalization in the egg cortical region. Using a functional assay, we demonstrated that microinjection of recombinant, prenylated and active GST-Rab3A triggered cortical granule exocytosis, indicating that Rab3A has an active role in this secretory pathway. To confirm this active role, we inhibited the function of endogenous Rab3A by microinjecting a polyclonal antibody raised against Rab3A prior to parthenogenetic activation. Our results showed that Rab3A antibody microinjection abolished cortical granule exocytosis in parthenogenetically activated oocytes. Altogether, our findings confirm that Rab3A might function as a marker of cortical granules and participates in cortical granule exocytosis in mouse eggs. - Highlights: • Rab3A has a similar migration pattern to cortical granules in mouse oocytes. • Rab3A can be a marker of

  2. Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.

    Directory of Open Access Journals (Sweden)

    Amanda Worker

    Full Text Available Parkinson's disease (PD, Multiple System Atrophy (MSA and Progressive Supranuclear Palsy (PSP are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features.High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0. Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group.Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology.These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients.

  3. Autosomal dominant cortical tremor, myoclonus and epilepsy.

    Science.gov (United States)

    Striano, Pasquale; Zara, Federico

    2016-09-01

    The term 'cortical tremor' was first introduced by Ikeda and colleagues to indicate a postural and action-induced shivering movement of the hands which mimics essential tremor, but presents with the electrophysiological findings of cortical reflex myoclonus. The association between autosomal dominant cortical tremor, myoclonus and epilepsy (ADCME) was first recognized in Japanese families and is now increasingly reported worldwide, although it is described using different acronyms (BAFME, FAME, FEME, FCTE and others). The disease usually takes a benign course, although drug-resistant focal seizures or slight intellectual disability occur in some cases. Moreover, a worsening of cortical tremor and myoclonus is common in advanced age. Although not yet recognized by the International League Against Epilepsy (ILAE), this is a well-delineated epilepsy syndrome with remarkable features that clearly distinguishes it from other myoclonus epilepsies. Moreover, genetic studies of these families show heterogeneity and different susceptible chromosomal loci have been identified.

  4. MRI of focal cortical dysplasia

    International Nuclear Information System (INIS)

    Lee, B.C.P.; Hatfield, G.A.; Bourgeois, B.; Park, T.S.

    1998-01-01

    We studied nine cases of focal cortical dysplasia (FCD) by MRI, with surface-rendered 3D reconstructions. One case was also examined using single-voxel proton MR spectroscopy (MRS). The histological features were reviewed and correlated with the MRI findings. The gyri affected by FCD were enlarged and the signal of the cortex was slightly increased on T1-weighted images. The gray-white junction was indistinct. Signal from the subcortical white matter was decreased on T1- and increased on T2-weighted images in most cases. Contrast enhancement was seen in two cases. Proton MRS showed a spectrum identical to that of normal brain. (orig.) (orig.)

  5. Which are risk factors developing renal cortical defects on {sup 99m}Tc-DMSA scintigraphy in children with acute urinary tract infections?

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Seong Won; Lim, Gye Yeon; Jang, Hae Suk; Lee, Eun Ja; Sohn, Hyung Sun; Hahn, Sung Tae [The Catholic University, Seoul (Korea, Republic of)

    2000-04-01

    To determine (1) the relationship between the cortical defects seen on {sup 99}''mTc-DMSA renal scans and age, and (2) the presence and degree of vesicoureteral reflux, and then to depict the risk factors for cortical defects in children with acute urinary tract infection (UTI). Furthermore, to assess the diagnostic value of VCUG in predicting a defect on {sup 99m}Tc-DMSA renal scans. We studied 134 kidneys in 67 children aged 15 days-10 years (M:F =3D 39:28) in whom symptomatic UTI was present. In all these children, both DMSA renal scans and voiding cystourethrography (VCUG) were performed. Scanning took place within 7 days of diagnosis and VCUG was performed after one month of diagnosis. Scintigraphic findings were graded according to the extent and number of cortical defects. We evaluated the relationships between the cortical defects seen on DMSA scans and age, and the grade of vesicoureteral reflux. The diagnostic value of VCUG in predicting cortical defects was analysed. The prevalence of cortical defects was greater in patients older than two years (38/54, 70%) than in those aged less than two (38/80, 48%). The frequency of cortical defects was related to vesicoureteral reflux (p less than 0.05) and grade of reflux (p less than 0.05). As this latter increased, the extent of cortical defects also increased (p less than 0.05), and DMSA scans revealed the presence of these in 76 of the 134 kidneys (57%) with acute UTI. In 30 of these 76 (39.5%), VCUG demonstrated the presence of vesicoureteral reflex. On the other hand, vesicoureteral reflex was found in 36 of the 134 kidneys (27%), and in 30 of these 36 (83%), cortical defects were noted. The sensitivity of VCUG in predicting cortical defect was 39.5%, while specificity was 89.7%. The positive predictive value for defects was 83.3%, and the negative predictive value was 53.1%. The relative risk of cortical defect in the presence of vesicoureteral reflux was 1.78. Renal cortical defects are

  6. Which are risk factors developing renal cortical defects on 99mTc-DMSA scintigraphy in children with acute urinary tract infections?

    International Nuclear Information System (INIS)

    Moon, Seong Won; Lim, Gye Yeon; Jang, Hae Suk; Lee, Eun Ja; Sohn, Hyung Sun; Hahn, Sung Tae

    2000-01-01

    To determine (1) the relationship between the cortical defects seen on 99 ''mTc-DMSA renal scans and age, and (2) the presence and degree of vesicoureteral reflux, and then to depict the risk factors for cortical defects in children with acute urinary tract infection (UTI). Furthermore, to assess the diagnostic value of VCUG in predicting a defect on 99m Tc-DMSA renal scans. We studied 134 kidneys in 67 children aged 15 days-10 years (M:F =3D 39:28) in whom symptomatic UTI was present. In all these children, both DMSA renal scans and voiding cystourethrography (VCUG) were performed. Scanning took place within 7 days of diagnosis and VCUG was performed after one month of diagnosis. Scintigraphic findings were graded according to the extent and number of cortical defects. We evaluated the relationships between the cortical defects seen on DMSA scans and age, and the grade of vesicoureteral reflux. The diagnostic value of VCUG in predicting cortical defects was analysed. The prevalence of cortical defects was greater in patients older than two years (38/54, 70%) than in those aged less than two (38/80, 48%). The frequency of cortical defects was related to vesicoureteral reflux (p less than 0.05) and grade of reflux (p less than 0.05). As this latter increased, the extent of cortical defects also increased (p less than 0.05), and DMSA scans revealed the presence of these in 76 of the 134 kidneys (57%) with acute UTI. In 30 of these 76 (39.5%), VCUG demonstrated the presence of vesicoureteral reflex. On the other hand, vesicoureteral reflex was found in 36 of the 134 kidneys (27%), and in 30 of these 36 (83%), cortical defects were noted. The sensitivity of VCUG in predicting cortical defect was 39.5%, while specificity was 89.7%. The positive predictive value for defects was 83.3%, and the negative predictive value was 53.1%. The relative risk of cortical defect in the presence of vesicoureteral reflux was 1.78. Renal cortical defects are significantly related to age

  7. Influence of mesh density, cortical thickness and material properties on human rib fracture prediction.

    Science.gov (United States)

    Li, Zuoping; Kindig, Matthew W; Subit, Damien; Kent, Richard W

    2010-11-01

    The purpose of this paper was to investigate the sensitivity of the structural responses and bone fractures of the ribs to mesh density, cortical thickness, and material properties so as to provide guidelines for the development of finite element (FE) thorax models used in impact biomechanics. Subject-specific FE models of the second, fourth, sixth and tenth ribs were developed to reproduce dynamic failure experiments. Sensitivity studies were then conducted to quantify the effects of variations in mesh density, cortical thickness, and material parameters on the model-predicted reaction force-displacement relationship, cortical strains, and bone fracture locations for all four ribs. Overall, it was demonstrated that rib FE models consisting of 2000-3000 trabecular hexahedral elements (weighted element length 2-3mm) and associated quadrilateral cortical shell elements with variable thickness more closely predicted the rib structural responses and bone fracture force-failure displacement relationships observed in the experiments (except the fracture locations), compared to models with constant cortical thickness. Further increases in mesh density increased computational cost but did not markedly improve model predictions. A ±30% change in the major material parameters of cortical bone lead to a -16.7 to 33.3% change in fracture displacement and -22.5 to +19.1% change in the fracture force. The results in this study suggest that human rib structural responses can be modeled in an accurate and computationally efficient way using (a) a coarse mesh of 2000-3000 solid elements, (b) cortical shells elements with variable thickness distribution and (c) a rate-dependent elastic-plastic material model. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

  8. Aberrant cortical associative plasticity associated with severe adult Tourette syndrome.

    Science.gov (United States)

    Martín-Rodríguez, Juan Francisco; Ruiz-Rodríguez, María Adilia; Palomar, Francisco J; Cáceres-Redondo, María Teresa; Vargas, Laura; Porcacchia, Paolo; Gómez-Crespo, Mercedes; Huertas-Fernández, Ismael; Carrillo, Fátima; Madruga-Garrido, Marcos; Mir, Pablo

    2015-03-01

    Recent studies have shown altered cortical plasticity in adult patients with Tourette syndrome. However, the clinical significance of this finding remains elusive. Motor cortical plasticity was evaluated in 15 adult patients with severe Tourette syndrome and 16 healthy controls using the paired associative stimulation protocol by transcranial magnetic stimulation. Associations between paired associative stimulation-induced plasticity and relevant clinical variables, including cortical excitability, psychiatric comorbidities, drug treatment and tic severity, were assessed. Motor cortical plasticity was abnormally increased in patients with Tourette syndrome compared with healthy subjects. This abnormal plasticity was independently associated with tic severity. Patients with severe Tourette syndrome display abnormally increased cortical associative plasticity. This aberrant cortical plasticity was associated with tic severity, suggesting an underlying mechanism for tic pathophysiology. © 2015 International Parkinson and Movement Disorder Society.

  9. Deficits in Beam-Walking After Neonatal Motor Cortical Lesions are not Spared by Fetal Cortical Transplants in Rats

    OpenAIRE

    Swenson, R. S.; Danielsen, E. H.; Klausen, B. S.; Erlich, E.; Zimmer, J.; Castro, A. J.

    1989-01-01

    Adult rats that sustained unilateral motor cortical lesions at birth demonstrated deficits in traversing an elevated narrow beam. These deficits, manifested by hindlimb slips off the edge of the beam, were not spared in animals that received fetal cortical transplants into the lesion cavity immediately after lesion placement.

  10. Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons.

    Science.gov (United States)

    Xiao, Dongsheng; Vanni, Matthieu P; Mitelut, Catalin C; Chan, Allen W; LeDue, Jeffrey M; Xie, Yicheng; Chen, Andrew Cn; Swindale, Nicholas V; Murphy, Timothy H

    2017-02-04

    Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity. Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function. This approach can define network relationships between any point source of neuronal spiking and mesoscale cortical maps.

  11. TDCS modulates cortical excitability in patients with disorders of consciousness

    Directory of Open Access Journals (Sweden)

    Yang Bai

    2017-01-01

    Full Text Available Transcranial direct current stimulation (tDCS has been reported to be a promising technique for consciousness improvement for patients with disorders of consciousness (DOC. However, there has been no direct electrophysiological evidence to demonstrate the efficacy of tDCS on patients with DOC. Therefore, we aim to measure the cortical excitability changes induced by tDCS in patients with DOC, to find electrophysiological evidence supporting the therapeutic efficacy of tDCS on patients with DOC. In this study, we enrolled sixteen patients with DOC, including nine vegetative state (VS and seven minimally conscious state (MCS (six females and ten males. TMS-EEG was applied to assess cortical excitability changes after twenty minutes of anodal tDCS of the left dorsolateral prefrontal cortex. Global cerebral excitability were calculated to quantify cortical excitability in the temporal domain: four time intervals (0–100, 100–200, 200–300, 300-400 ms. Then local cerebral excitability in the significantly altered time windows were investigated (frontal, left/right hemispheres, central, and posterior. Compared to baseline and sham stimulation, we found that global cerebral excitability increased in early time windows (0–100 and 100-200 ms for patients with MCS; for the patients with VS, global cerebral excitability increased in the 0-100 ms interval but decreased in the 300-400 ms interval. The local cerebral excitability was significantly different between MCS and VS. The results indicated that tDCS can effectively modulate the cortical excitability of patients with DOC; and the changes in excitability in temporal and spatial domains are different between patients with MCS and those with VS.

  12. Delineation of cortical pathology in multiple sclerosis using multi-surface magnetization transfer ratio imaging

    Directory of Open Access Journals (Sweden)

    David A. Rudko

    2016-01-01

    Full Text Available The purpose of our study was to evaluate the utility of measurements of cortical surface magnetization transfer ratio (csMTR on the inner, mid and outer cortical boundaries as clinically accessible biomarkers of cortical gray matter pathology in multiple sclerosis (MS. Twenty-five MS patients and 12 matched controls were recruited from the MS Clinic of the Montreal Neurological Institute. Anatomical and magnetization transfer ratio (MTR images were acquired using 3 Tesla MRI at baseline and two-year time-points. MTR maps were smoothed along meshes representing the inner, mid and outer neocortical boundaries. To evaluate csMTR reductions suggestive of sub-pial demyelination in MS patients, a mixed model analysis was carried out at both the individual vertex level and in anatomically parcellated brain regions. Our results demonstrate that focal areas of csMTR reduction are most prevalent along the outer cortical surface in the superior temporal and posterior cingulate cortices, as well as in the cuneus and precentral gyrus. Additionally, age regression analysis identified that reductions of csMTR in MS patients increase with age but appear to hit a plateau in the outer caudal anterior cingulate, as well as in the precentral and postcentral cortex. After correction for the naturally occurring gradient in cortical MTR, the difference in csMTR between the inner and outer cortex in focal areas in the brains of MS patients correlated with clinical disability. Overall, our findings support multi-surface analysis of csMTR as a sensitive marker of cortical sub-pial abnormality indicative of demyelination in MS patients.

  13. Cortical myoclonus and cerebellar pathology

    NARCIS (Netherlands)

    Tijssen, MAJ; Thom, M; Ellison, DW; Wilkins, P; Barnes, D; Thompson, PD; Brown, P

    2000-01-01

    Objective To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. Background: The pathologic findings in conditions associated with cortical myoclonus commonly involve

  14. Cortical myoclonus and cerebellar pathology

    NARCIS (Netherlands)

    Tijssen, M. A.; Thom, M.; Ellison, D. W.; Wilkins, P.; Barnes, D.; Thompson, P. D.; Brown, P.

    2000-01-01

    OBJECTIVE: To study the electrophysiologic and pathologic findings in three patients with cortical myoclonus. In two patients the myoclonic ataxic syndrome was associated with proven celiac disease. BACKGROUND: The pathologic findings in conditions associated with cortical myoclonus commonly involve

  15. Characterization of Early Cortical Neural Network ...

    Science.gov (United States)

    We examined the development of neural network activity using microelectrode array (MEA) recordings made in multi-well MEA plates (mwMEAs) over the first 12 days in vitro (DIV). In primary cortical cultures made from postnatal rats, action potential spiking activity was essentially absent on DIV 2 and developed rapidly between DIV 5 and 12. Spiking activity was primarily sporadic and unorganized at early DIV, and became progressively more organized with time in culture, with bursting parameters, synchrony and network bursting increasing between DIV 5 and 12. We selected 12 features to describe network activity and principal components analysis using these features demonstrated a general segregation of data by age at both the well and plate levels. Using a combination of random forest classifiers and Support Vector Machines, we demonstrated that 4 features (CV of within burst ISI, CV of IBI, network spike rate and burst rate) were sufficient to predict the age (either DIV 5, 7, 9 or 12) of each well recording with >65% accuracy. When restricting the classification problem to a binary decision, we found that classification improved dramatically, e.g. 95% accuracy for discriminating DIV 5 vs DIV 12 wells. Further, we present a novel resampling approach to determine the number of wells that might be needed for conducting comparisons of different treatments using mwMEA plates. Overall, these results demonstrate that network development on mwMEA plates is similar to

  16. Overweight is not associated with cortical thickness alterations in children

    Directory of Open Access Journals (Sweden)

    Rachel Jane Sharkey

    2015-02-01

    Full Text Available IntroductionSeveral studies report an association between body mass index (BMI and cortical thickness in adults. Some studies demonstrate diffuse cortical thinning in obesity, while others report effects in areas that are associated with self-regulation, such as lateral prefrontal cortex. MethodsThis study used multilevel modelling of data from the NIH Pediatric MRI Data Repository, a mixed longitudinal and cross-sectional database, to examine the relationship between cortical thickness and body weight in children. Cortical thickness was computed at 81,942 vertices of 716 MRI scans from 378 children aged between 4 and 18 years. Body mass index Z score for age was computed for each participant. We preformed vertex-wise statistical analysis of the relationship between cortical thickness and BMI, accounting for age and gender. In addition, cortical thickness was extracted from regions of interest in prefrontal cortex and insula.ResultsNo significant association between cortical thickness and BMI was found, either by statistical parametric mapping or by region of interest analysis. Results remained negative when the analysis was restricted to children aged 12-18.ConclusionsThe correlation between BMI and cortical thickness was not found in this large pediatric sample. The association between BMI and cortical thinning develops after adolescence. This has implications for the nature of the relationship between brain anatomy and weight gain.

  17. Pronounced prefronto-temporal cortical thinning in schizophrenia: Neuroanatomical correlate of suicidal behavior?

    Science.gov (United States)

    Besteher, Bianca; Wagner, Gerd; Koch, Kathrin; Schachtzabel, Claudia; Reichenbach, Jürgen R; Schlösser, Ralf; Sauer, Heinrich; Schultz, C Christoph

    2016-10-01

    Schizophrenia is characterized by increased mortality for which suicidality is the decisive factor. An analysis of cortical thickness and folding to further elucidate neuroanatomical correlates of suicidality in schizophrenia has not yet been performed. We searched for relevant brain regions with such differences between patients with suicide-attempts, patients without any suicidal thoughts and healthy controls. 37 schizophrenia patients (14 suicide-attempters and 23 non-suicidal) and 50 age- and gender-matched healthy controls were included. Suicidality was documented through clinical interview and chart review. All participants underwent T1-weighted MRI scans. Whole brain node-by-node cortical thickness and folding were estimated (FreeSurfer Software) and compared. Additionally a three group comparison for prefrontal regions-of-interest was performed in SPSS using a multifactorial GLM. Compared with the healthy controls patients showed a typical pattern of cortical thinning in prefronto-temporal regions and altered cortical folding in the right medial temporal cortex. Patients with suicidal behavior compared with non-suicidal patients demonstrated pronounced (psuicidal patients with non-suicidal patients significant (psuicidal behaviour in schizophrenia. We identified cortical thinning in a network strongly involved in regulation of impulsivity, emotions and planning of behaviour in suicide attempters, which might lead to neuronal dysregulation in this network and consequently to a higher risk of suicidal behavior. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Clozapine potentiation of GABA mediated cortical inhibition in treatment resistant schizophrenia.

    Science.gov (United States)

    Kaster, Tyler S; de Jesus, Danilo; Radhu, Natasha; Farzan, Faranak; Blumberger, Daniel M; Rajji, Tarek K; Fitzgerald, Paul B; Daskalakis, Zafiris J

    2015-07-01

    Cortical inhibition (CI) deficits have been demonstrated in schizophrenia using transcranial magnetic stimulation (TMS). These CI deficits may be related to decreased GABA activity which may be involved in schizophrenia pathophysiology. Previous cross-sectional studies have also demonstrated greater CI in patients treated with clozapine than other typical/atypical antipsychotics. However, it is not clear if these differences in CI are a result of treatment-resistant illness which necessitates clozapine or are related to clozapine treatment. TMS measures of CI (i.e., cortical silent period (CSP) and short-interval cortical inhibition (SICI)) were measured over the motor cortex in 16 patients with schizophrenia before starting clozapine, then 6 weeks and 6 months after starting clozapine. CSP was significantly longer after 6 weeks of treatment with clozapine (p=0.014). From 6 weeks to 6 months, there was no significant difference in CSP (p>0.05). Short-interval cortical inhibition (SICI) was not significantly different at any time after treatment with clozapine (p>0.05). This prospective-longitudinal study demonstrates that treatment with clozapine is associated with an increase in GABAB mediated inhibitory neurotransmission. Potentiation of GABAB may be a novel neurotransmitter mechanism that is involved in the pathophysiology and treatment of schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Cortical influences drive amyotrophic lateral sclerosis.

    Science.gov (United States)

    Eisen, Andrew; Braak, Heiko; Del Tredici, Kelly; Lemon, Roger; Ludolph, Albert C; Kiernan, Matthew C

    2017-11-01

    The early motor manifestations of sporadic amyotrophic lateral sclerosis (ALS), while rarely documented, reflect failure of adaptive complex motor skills. The development of these skills correlates with progressive evolution of a direct corticomotoneuronal system that is unique to primates and markedly enhanced in humans. The failure of this system in ALS may translate into the split hand presentation, gait disturbance, split leg syndrome and bulbar symptomatology related to vocalisation and breathing, and possibly diffuse fasciculation, characteristic of ALS. Clinical neurophysiology of the brain employing transcranial magnetic stimulation has convincingly demonstrated a presymptomatic reduction or absence of short interval intracortical inhibition, accompanied by increased intracortical facilitation, indicating cortical hyperexcitability. The hallmark of the TDP-43 pathological signature of sporadic ALS is restricted to cortical areas as well as to subcortical nuclei that are under the direct control of corticofugal projections. This provides anatomical support that the origins of the TDP-43 pathology reside in the cerebral cortex itself, secondarily in corticofugal fibres and the subcortical targets with which they make monosynaptic connections. The latter feature explains the multisystem degeneration that characterises ALS. Consideration of ALS as a primary neurodegenerative disorder of the human brain may incorporate concepts of prion-like spread at synaptic terminals of corticofugal axons. Further, such a concept could explain the recognised widespread imaging abnormalities of the ALS neocortex and the accepted relationship between ALS and frontotemporal dementia. © 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.

  20. Assessment of cortical maturation with prenatal MRI. Part I: normal cortical maturation

    International Nuclear Information System (INIS)

    Fogliarini, Celine; Chaumoitre, Katia; Chapon, Frederique; Levrier, Olivier; Girard, Nadine; Fernandez, Carla; Figarella-Branger, Dominique

    2005-01-01

    Cortical maturation, especially gyral formation, follows a temporospatial schedule and is a good marker of fetal maturation. Although ultrasonography is still the imaging method of choice to evaluate fetal anatomy, MRI has an increasingly important role in the detection of brain abnormalities, especially of cortical development. Knowledge of MRI techniques in utero with the advantages and disadvantages of some sequences is necessary, in order to try to optimize the different magnetic resonance sequences to be able to make an early diagnosis. The different steps of cortical maturation known from histology represent the background necessary for the understanding of maturation in order to be then able to evaluate brain maturation through neuroimaging. Illustrations of the normal cortical maturation are given for each step accessible to MRI for both the cerebral hemispheres and the posterior fossa. (orig.)

  1. Assessment of cortical maturation with prenatal MRI. Part I: normal cortical maturation

    Energy Technology Data Exchange (ETDEWEB)

    Fogliarini, Celine [Faculte Timone, Centre de Resonance Magnetique Biologique et Medicale, Marseille (France); Chaumoitre, Katia [Hopital Nord, Department of Radiology, Marseille (France); Chapon, Frederique; Levrier, Olivier; Girard, Nadine [Hopital Timone, Department of Neuroradiology, Marseille Cedex 5 (France); Fernandez, Carla; Figarella-Branger, Dominique [Hopital Timone, Department of Pathology, Marseille (France)

    2005-08-01

    Cortical maturation, especially gyral formation, follows a temporospatial schedule and is a good marker of fetal maturation. Although ultrasonography is still the imaging method of choice to evaluate fetal anatomy, MRI has an increasingly important role in the detection of brain abnormalities, especially of cortical development. Knowledge of MRI techniques in utero with the advantages and disadvantages of some sequences is necessary, in order to try to optimize the different magnetic resonance sequences to be able to make an early diagnosis. The different steps of cortical maturation known from histology represent the background necessary for the understanding of maturation in order to be then able to evaluate brain maturation through neuroimaging. Illustrations of the normal cortical maturation are given for each step accessible to MRI for both the cerebral hemispheres and the posterior fossa. (orig.)

  2. Mean cortical curvature reflects cytoarchitecture restructuring in mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Jace B. King

    2016-01-01

    Full Text Available In the United States alone, the number of persons living with the enduring consequences of traumatic brain injuries is estimated to be between 3.2 and 5 million. This number does not include individuals serving in the United States military or seeking care at Veterans Affairs hospitals. The importance of understanding the neurobiological consequences of mild traumatic brain injury (mTBI has increased with the return of veterans from conflicts overseas, many of who have suffered this type of brain injury. However, identifying the neuroanatomical regions most affected by mTBI continues to prove challenging. The aim of this study was to assess the use of mean cortical curvature as a potential indicator of progressive tissue loss in a cross-sectional sample of 54 veterans with mTBI compared to 31 controls evaluated with MRI. It was hypothesized that mean cortical curvature would be increased in veterans with mTBI, relative to controls, due in part to cortical restructuring related to tissue volume loss. Mean cortical curvature was assessed in 60 bilateral regions (31 sulcal, 29 gyral. Of the 120 regions investigated, nearly 50% demonstrated significantly increased mean cortical curvature in mTBI relative to controls with 25% remaining significant following multiple comparison correction (all, pFDR < .05. These differences were most prominent in deep gray matter regions of the cortex. Additionally, significant relationships were found between mean cortical curvature and gray and white matter volumes (all, p < .05. These findings suggest potentially unique patterns of atrophy by region and indicate that changes in brain microstructure due to mTBI are sensitive to measures of mean curvature.

  3. Altered inhibition in Tuberous Sclerosis and Type IIb cortical dysplasia

    Science.gov (United States)

    Talos, Delia M.; Sun, Hongyu; Kosaras, Bela; Joseph, Annelise; Folkerth, Rebecca D.; Poduri, Annapurna; Madsen, Joseph R.; Black, Peter M.; Jensen, Frances E.

    2012-01-01

    Objective The most common neurological symptom of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) is early-life refractory epilepsy. As previous studies have shown enhanced excitatory glutamatergic neurotransmission in TSC and FCD brains, we hypothesized that neurons associated with these lesions may also express altered GABAA receptor (GABAAR)-mediated inhibition. Methods Expression of the GABAAR subunitsα1 and α4, the Na+-K+-2Cl− (NKCC1), and the K+−Cl− (KCC2) transporters in human TSC and FCD Type II specimens were analyzed by Western blot and double label immunocytochemistry. GABAAR responses in dysplastic neurons from a single case of TSC were measured by perforated-patch recording and compared to normal-appearing cortical neurons from a non-TSC epilepsy case. Results TSC and FCD Type IIb lesions demonstrated decreased expression of the GABAAR α1, increased NKCC1 and decreased KCC2 levels. In contrast, FCD Type IIa lesions showed decreased α4, and increased expression of both NKCC1 and KCC2 transporters. Patch clamp recordings from dysplastic neurons in acute slices from TSC tubers demonstrated excitatory GABAAR responses that were significantly attenuated by the NKCC1 inhibitor bumetanide, in contrast to hyperpolarizing GABAAR-mediated currents in normal neurons from non-TSC cortical slices. Interpretation Expression and function of GABAARs in TSC and FCD IIb suggests the relative benzodiazepine insensitivity and more excitatory action of GABA compared to FCD IIa. These factors may contribute to resistance of seizure activity to anticonvulsants that increase GABAergic function, and may justify add-on trials of the NKCC1 inhibitor bumetanide for the treatment of TSC and FCD Type IIb related epilepsy. PMID:22447678

  4. PET in malformations of cortical development

    International Nuclear Information System (INIS)

    Bouilleret, V.; O'Brien, T.J.; Bouilleret, V.; Bouilleret, V.; Chiron, C.; Chiron, C.

    2009-01-01

    Within the group of malformations of cortical development, focal cortical dysplasia (FCD) are an increasingly recognized cause of intractable epilepsy that can be cured by surgery. The success of cortical resection for intractable epilepsy is highly dependent on the accurate pre-surgical delineation of the regions responsible for generating seizures. [ 18 F]-FDG PET, which images cerebral metabolism studying brain glucose uptake, is the most established functional imaging modality in the evaluation of patients with epilepsy. The aim of this article is to review [ 18 F]-FDG PET usefulness as a pre-surgical tool in the evaluation of medically refractory partial epilepsy. It has an established place in assisting in the localisation and definition of FCD in patients with no lesion, or only a subtle abnormality, on MRI. The role of FDG-PET in defining the extent of the surgical resection is still uncertain and needs to be the focus of future research. (authors)

  5. Assessing policy options for increasing the use of renewable energy for sustainable development: Modelling energy scenarios for Sichuan, China. A UN-ENERGY demonstration study

    International Nuclear Information System (INIS)

    2007-01-01

    policies to increase the share of renewables in the energy supply mix of Sichuan, China. It was initiated in response to the Johannesburg Plan of Implementation's call to 'with a sense of urgency, substantially increase the global share of renewable energy sources'. The study again combines the IAEA models for analyzing national energy systems with data provided by UNEP, DESA and other public sources. It is important to note that this is a demonstration study, not a comprehensive analysis of policy options for Sichuan, but it provides generic insights on policy options to promote the use of renewable energy sources. The study also demonstrates the kind of policy work that UN-Energy can undertake as it seeks to evolve the joint capacity of the UN system to assist nations in facing the energy challenges of the 21st century. UN-Energy seeks to institutionalize a collaborative approach in an area that has not previously been subject to such approaches in the UN system. UNEnergy would appreciate views by readers of our reports in order to guide our future work

  6. Cortical representations of communication sounds.

    Science.gov (United States)

    Heiser, Marc A; Cheung, Steven W

    2008-10-01

    This review summarizes recent research into cortical processing of vocalizations in animals and humans. There has been a resurgent interest in this topic accompanied by an increased number of studies using animal models with complex vocalizations and new methods in human brain imaging. Recent results from such studies are discussed. Experiments have begun to reveal the bilateral cortical fields involved in communication sound processing and the transformations of neural representations that occur among those fields. Advances have also been made in understanding the neuronal basis of interaction between developmental exposures and behavioral experiences with vocalization perception. Exposure to sounds during the developmental period produces large effects on brain responses, as do a variety of specific trained tasks in adults. Studies have also uncovered a neural link between the motor production of vocalizations and the representation of vocalizations in cortex. Parallel experiments in humans and animals are answering important questions about vocalization processing in the central nervous system. This dual approach promises to reveal microscopic, mesoscopic, and macroscopic principles of large-scale dynamic interactions between brain regions that underlie the complex phenomenon of vocalization perception. Such advances will yield a greater understanding of the causes, consequences, and treatment of disorders related to speech processing.

  7. Abnormalities in Structural Covariance of Cortical Gyrification in Parkinson's Disease.

    Science.gov (United States)

    Xu, Jinping; Zhang, Jiuquan; Zhang, Jinlei; Wang, Yue; Zhang, Yanling; Wang, Jian; Li, Guanglin; Hu, Qingmao; Zhang, Yuanchao

    2017-01-01

    Although abnormal cortical morphology and connectivity between brain regions (structural covariance) have been reported in Parkinson's disease (PD), the topological organizations of large-scale structural brain networks are still poorly understood. In this study, we investigated large-scale structural brain networks in a sample of 37 PD patients and 34 healthy controls (HC) by assessing the structural covariance of cortical gyrification with local gyrification index (lGI). We demonstrated prominent small-world properties of the structural brain networks for both groups. Compared with the HC group, PD patients showed significantly increased integrated characteristic path length and integrated clustering coefficient, as well as decreased integrated global efficiency in structural brain networks. Distinct distributions of hub regions were identified between the two groups, showing more hub regions in the frontal cortex in PD patients. Moreover, the modular analyses revealed significantly decreased integrated regional efficiency in lateral Fronto-Insula-Temporal module, and increased integrated regional efficiency in Parieto-Temporal module in the PD group as compared to the HC group. In summary, our study demonstrated altered topological properties of structural networks at a global, regional and modular level in PD patients. These findings suggests that the structural networks of PD patients have a suboptimal topological organization, resulting in less effective integration of information between brain regions.

  8. Development of cortical asymmetry in typically developing children and its disruption in attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Shaw, Philip; Lalonde, Francois; Lepage, Claude; Rabin, Cara; Eckstrand, Kristen; Sharp, Wendy; Greenstein, Deanna; Evans, Alan; Giedd, J N; Rapoport, Judith

    2009-08-01

    Just as typical development of anatomical asymmetries in the human brain has been linked with normal lateralization of motor and cognitive functions, disruption of asymmetry has been implicated in the pathogenesis of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). No study has examined the development of cortical asymmetry using longitudinal neuroanatomical data. To delineate the development of cortical asymmetry in children with and without ADHD. Longitudinal study. Government Clinical Research Institute. A total of 218 children with ADHD and 358 typically developing children, from whom 1133 neuroanatomical magnetic resonance images were acquired prospectively. Cortical thickness was estimated at 40 962 homologous points in the left and right hemispheres, and the trajectory of change in asymmetry was defined using mixed-model regression. In right-handed typically developing individuals, a mean (SE) increase in the relative thickness of the right orbitofrontal and inferior frontal cortex with age of 0.011 (0.0018) mm per year (t(337) = 6.2, P left-hemispheric increase in the occipital cortical regions of 0.013 (0.0015) mm per year (t(337) = 8.1, P right-handed typically developing individuals was less extensive and was localized to different cortical regions. In ADHD, the posterior component of this evolving asymmetry was intact, but the prefrontal component was lost. These findings explain the way that, in typical development, the increased dimensions of the right frontal and left occipital cortical regions emerge in adulthood from the reversed pattern of childhood cortical asymmetries. Loss of the prefrontal component of this evolving asymmetry in ADHD is compatible with disruption of prefrontal function in the disorder and demonstrates the way that disruption of typical processes of asymmetry can inform our understanding of neurodevelopmental disorders.

  9. Sonic hedgehog promotes neurite outgrowth of cortical neurons under oxidative stress: Involving of mitochondria and energy metabolism.

    Science.gov (United States)

    He, Weiliang; Cui, Lili; Zhang, Cong; Zhang, Xiangjian; He, Junna; Xie, Yanzhao; Chen, Yanxia

    2017-01-01

    Oxidative stress has been demonstrated to be involved in the etiology of several neurobiological disorders. Sonic hedgehog (Shh), a secreted glycoprotein factor, has been implicated in promoting several aspects of brain remodeling process. Mitochondria may play an important role in controlling fundamental processes in neuroplasticity. However, little evidence is available about the effect and the potential mechanism of Shh on neurite outgrowth in primary cortical neurons under oxidative stress. Here, we revealed that Shh treatment significantly increased the viability of cortical neurons in a dose-dependent manner, which was damaged by hydrogen peroxide (H 2 O 2 ). Shh alleviated the apoptosis rate of H 2 O 2 -induced neurons. Shh also increased neuritogenesis injuried by H 2 O 2 in primary cortical neurons. Moreover, Shh reduced the generation of reactive oxygen species (ROS), increased the activities of SOD and and decreased the productions of MDA. In addition, Shh protected mitochondrial functions, elevated the cellular ATP levels and amelioratesd the impairment of mitochondrial complex II activities of cortical neurons induced by H 2 O 2 . In conclusion, all these results suggest that Shh acts as a prosurvival factor playing an essential role to neurite outgrowth of cortical neuron under H 2 O 2 -induced oxidative stress, possibly through counteracting ROS release and preventing mitochondrial dysfunction and ATP as well as mitochondrial complex II activities against oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Background noise exerts diverse effects on the cortical encoding of foreground sounds.

    Science.gov (United States)

    Malone, B J; Heiser, Marc A; Beitel, Ralph E; Schreiner, Christoph E

    2017-08-01

    In natural listening conditions, many sounds must be detected and identified in the context of competing sound sources, which function as background noise. Traditionally, noise is thought to degrade the cortical representation of sounds by suppressing responses and increasing response variability. However, recent studies of neural network models and brain slices have shown that background synaptic noise can improve the detection of signals. Because acoustic noise affects the synaptic background activity of cortical networks, it may improve the cortical responses to signals. We used spike train decoding techniques to determine the functional effects of a continuous white noise background on the responses of clusters of neurons in auditory cortex to foreground signals, specifically frequency-modulated sweeps (FMs) of different velocities, directions, and amplitudes. Whereas the addition of noise progressively suppressed the FM responses of some cortical sites in the core fields with decreasing signal-to-noise ratios (SNRs), the stimulus representation remained robust or was even significantly enhanced at specific SNRs in many others. Even though the background noise level was typically not explicitly encoded in cortical responses, significant information about noise context could be decoded from cortical responses on the basis of how the neural representation of the foreground sweeps was affected. These findings demonstrate significant diversity in signal in noise processing even within the core auditory fields that could support noise-robust hearing across a wide range of listening conditions. NEW & NOTEWORTHY The ability to detect and discriminate sounds in background noise is critical for our ability to communicate. The neural basis of robust perceptual performance in noise is not well understood. We identified neuronal populations in core auditory cortex of squirrel monkeys that differ in how they process foreground signals in background noise and that may

  11. Influences of brain development and ageing on cortical interactive networks.

    Science.gov (United States)

    Zhu, Chengyu; Guo, Xiaoli; Jin, Zheng; Sun, Junfeng; Qiu, Yihong; Zhu, Yisheng; Tong, Shanbao

    2011-02-01

    To study the effect of brain development and ageing on the pattern of cortical interactive networks. By causality analysis of multichannel electroencephalograph (EEG) with partial directed coherence (PDC), we investigated the different neural networks involved in the whole cortex as well as the anterior and posterior areas in three age groups, i.e., children (0-10 years), mid-aged adults (26-38 years) and the elderly (56-80 years). By comparing the cortical interactive networks in different age groups, the following findings were concluded: (1) the cortical interactive network in the right hemisphere develops earlier than its left counterpart in the development stage; (2) the cortical interactive network of anterior cortex, especially at C3 and F3, is demonstrated to undergo far more extensive changes, compared with the posterior area during brain development and ageing; (3) the asymmetry of the cortical interactive networks declines during ageing with more loss of connectivity in the left frontal and central areas. The age-related variation of cortical interactive networks from resting EEG provides new insights into brain development and ageing. Our findings demonstrated that the PDC analysis of EEG is a powerful approach for characterizing the cortical functional connectivity during brain development and ageing. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  12. The biology and dynamics of mammalian cortical granules

    Directory of Open Access Journals (Sweden)

    Liu Min

    2011-11-01

    Full Text Available Abstract Cortical granules are membrane bound organelles located in the cortex of unfertilized oocytes. Following fertilization, cortical granules undergo exocytosis to release their contents into the perivitelline space. This secretory process, which is calcium dependent and SNARE protein-mediated pathway, is known as the cortical reaction. After exocytosis, the released cortical granule proteins are responsible for blocking polyspermy by modifying the oocytes' extracellular matrices, such as the zona pellucida in mammals. Mammalian cortical granules range in size from 0.2 um to 0.6 um in diameter and different from most other regulatory secretory organelles in that they are not renewed once released. These granules are only synthesized in female germ cells and transform an egg upon sperm entry; therefore, this unique cellular structure has inherent interest for our understanding of the biology of fertilization. Cortical granules are long thought to be static and awaiting in the cortex of unfertilized oocytes to be stimulated undergoing exocytosis upon gamete fusion. Not till recently, the dynamic nature of cortical granules is appreciated and understood. The latest studies of mammalian cortical granules document that this organelle is not only biochemically heterogeneous, but also displays complex distribution during oocyte development. Interestingly, some cortical granules undergo exocytosis prior to fertilization; and a number of granule components function beyond the time of fertilization in regulating embryonic cleavage and preimplantation development, demonstrating their functional significance in fertilization as well as early embryonic development. The following review will present studies that investigate the biology of cortical granules and will also discuss new findings that uncover the dynamic aspect of this organelle in mammals.

  13. Muscarinic contribution to the acute cortical effects of vagus nerve stimulation

    Science.gov (United States)

    Nichols, Justin A.

    2011-12-01

    Electrical stimulation of the vagus nerve (VNS) has been used to treat more than 60,000 patients with drug-resistant epilepsy and is under investigation as a treatment for several other neurological disorders and conditions. Among these, VNS increases memory performance and enhances recovery of motor and cognitive function in animal models of traumatic brain injury. Recent research indicates that pairing brief VNS with tones multiple-times a day for several weeks induces long-term, input specific cortical plasticity, which can be used to re-normalize the pathological cortical reorganization and eliminate a behavioral correlate of chronic tinnitus in noise exposed rats. Despite the therapeutic potential, the mechanisms of action of VNS remain speculative. In chapter 2 of this dissertation, the acute effects of VNS on cortical synchrony, excitability, and temporal processing are examined. In anesthetized rats implanted with multi-electrode arrays, VNS increased and decorrelated spontaneous multi-unit activity, and suppressed entrainment to repetitive noise burst stimulation at 6 to 8 Hz, but not after systemic administration of the muscarinic antagonist scopolamine. Chapter 3 focuses on VNS-tone pairing induced cortical plasticity. Pairing VNS with a tone one hundred times in anesthetized rats resulted in frequency specific plasticity in 31% of the auditory cortex sites. Half of these sites exhibited a frequency specific increase in firing rate and half exhibited a frequency specific decrease. Muscarinic receptor blockade with scopolamine almost entirely prevented the frequency specific increases, but not decreases. Collectively, these experiments demonstrate the capacity for VNS to not only acutely influence cortical synchrony, and excitability, but to also influence temporal and spectral tuning via muscarinic receptor activation. These results strengthen the hypothesis that acetylcholine and muscarinic receptors are involved in the mechanisms of action of VNS and

  14. Censoring distances based on labeled cortical distance maps in cortical morphometry.

    Science.gov (United States)

    Ceyhan, Elvan; Nishino, Tomoyuki; Alexopolous, Dimitrios; Todd, Richard D; Botteron, Kelly N; Miller, Michael I; Ratnanather, J Tilak

    2013-01-01

    It has been demonstrated that shape differences in cortical structures may be manifested in neuropsychiatric disorders. Such morphometric differences can be measured by labeled cortical distance mapping (LCDM) which characterizes the morphometry of the laminar cortical mantle of cortical structures. LCDM data consist of signed/labeled distances of gray matter (GM) voxels with respect to GM/white matter (WM) surface. Volumes and other summary measures for each subject and the pooled distances can help determine the morphometric differences between diagnostic groups, however they do not reveal all the morphometric information contained in LCDM distances. To extract more information from LCDM data, censoring of the pooled distances is introduced for each diagnostic group where the range of LCDM distances is partitioned at a fixed increment size; and at each censoring step, the distances not exceeding the censoring distance are kept. Censored LCDM distances inherit the advantages of the pooled distances but also provide information about the location of morphometric differences which cannot be obtained from the pooled distances. However, at each step, the censored distances aggregate, which might confound the results. The influence of data aggregation is investigated with an extensive Monte Carlo simulation analysis and it is demonstrated that this influence is negligible. As an illustrative example, GM of ventral medial prefrontal cortices (VMPFCs) of subjects with major depressive disorder (MDD), subjects at high risk (HR) of MDD, and healthy control (Ctrl) subjects are used. A significant reduction in laminar thickness of the VMPFC in MDD and HR subjects is observed compared to Ctrl subjects. Moreover, the GM LCDM distances (i.e., locations with respect to the GM/WM surface) for which these differences start to occur are determined. The methodology is also applicable to LCDM-based morphometric measures of other cortical structures affected by disease.

  15. Censoring Distances Based on Labeled Cortical Distance Maps in Cortical Morphometry

    Directory of Open Access Journals (Sweden)

    Elvan eCeyhan

    2013-10-01

    Full Text Available It has been demonstrated that shape differences are manifested in cortical structures due to neuropsychiatric disorders. Such morphometric differences can be measured by labeled cortical distance mapping (LCDM which characterizes the morphometry of the laminar cortical mantle of cortical structures. LCDM data consist of signed/labeled distances of gray matter (GM voxels with respect to GM/white matter (WM surface. Volumes and other summary measures for each subject and the pooled distances can help determine the morphometric differences between diagnostic groups, however they do not reveal all the morphometric information con-tained in LCDM distances. To extract more information from LCDM data, censoring of the pooled distances is introduced for each diagnostic group where the range of LCDM distances is partitioned at a fixed increment size; and at each censoring step, the distances not exceeding the censoring distance are kept. Censored LCDM distances inherit the advantages of the pooled distances but also provide information about the location of morphometric differences which cannot be obtained from the pooled distances. However, at each step, the censored distances aggregate, which might confound the results. The influence of data aggregation is investigated with an extensive Monte Carlo simulation analysis and it is demonstrated that this influence is negligible. As an illustrative example, GM of ventral medial prefrontal cortices (VMPFCs of subjects with major depressive disorder (MDD, subjects at high risk (HR of MDD, and healthy control (Ctrl subjects are used. A significant reduction in laminar thickness of the VMPFC in MDD and HR subjects is observed compared to Ctrl subjects. Moreover, the GM LCDM distances (i.e., locations with respect to the GM/WM surface for which these differences start to occur are determined. The methodology is also applicable to LCDM-based morphometric measures of other cortical structures affected by disease.

  16. Auditory cortical volumes and musical ability in Williams syndrome.

    Science.gov (United States)

    Martens, Marilee A; Reutens, David C; Wilson, Sarah J

    2010-07-01

    Individuals with Williams syndrome (WS) have been shown to have atypical morphology in the auditory cortex, an area associated with aspects of musicality. Some individuals with WS have demonstrated specific musical abilities, despite intellectual delays. Primary auditory cortex and planum temporale volumes were manually segmented in 25 individuals with WS and 25 control participants, and the participants also underwent testing of musical abilities. Left and right planum temporale volumes were significantly larger in the participants with WS than in controls, with no significant difference noted between groups in planum temporale asymmetry or primary auditory cortical volumes. Left planum temporale volume was significantly increased in a subgroup of the participants with WS who demonstrated specific musical strengths, as compared to the remaining WS participants, and was highly correlated with scores on a musical task. These findings suggest that differences in musical ability within WS may be in part associated with variability in the left auditory cortical region, providing further evidence of cognitive and neuroanatomical heterogeneity within this syndrome. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  17. The enemy within: propagation of aberrant corticostriatal learning to cortical function in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Jeff A Beeler

    2013-09-01

    Full Text Available Motor dysfunction in Parkinson’s disease is believed to arise primarily from pathophysiology in the dorsal striatum and its related corticostriatal and thalamostriatal circuits during progressive dopamine denervation. One function of these circuits is to provide a filter that selectively facilitates or inhibits cortical activity to optimize cortical processing, making motor responses rapid and efficient. Corticostriatal synaptic plasticity mediates the learning that underlies this performance-optimizing filter. Under dopamine denervation, corticostriatal plasticity is altered, resulting in aberrant learning that induces inappropriate basal ganglia filtering that impedes rather than optimizes cortical processing. Human imaging suggests that increased cortical activity may compensate for striatal dysfunction in PD patients. In this Perspective article, we consider how aberrant learning at corticostriatal synapses may impair cortical processing and learning and undermine potential cortical compensatory mechanisms. Blocking or remediating aberrant corticostriatal plasticity may protect cortical function and support cortical compensatory mechanisms mitigating the functional decline associated with progressive dopamine denervation.

  18. Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment.

    Science.gov (United States)

    Berkes, Pietro; Orbán, Gergo; Lengyel, Máté; Fiser, József

    2011-01-07

    The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.

  19. Cortical activity in tinnitus patients and its modification by phonostimulation

    Directory of Open Access Journals (Sweden)

    Katarzyna Pawlak-Osińska

    2013-04-01

    Full Text Available OBJECTIVE: The goal of this study was to observe spontaneous cortical activity and cortical activity modulated by tinnitus-matched sound in tinnitus patients and healthy subjects with no otoneurologic symptoms. METHOD: Data were prospectively collected from 50 tinnitus patients and 25 healthy subjects. Cortical activity was recorded in all subjects with eyes closed and open and during photostimulation, hyperventilation and acoustic stimulation using 19-channel quantitative electroencephalography. The sound applied in the tinnitus patients was individually matched with the ability to mask or equal the tinnitus. The maximal and mean amplitude of the delta, theta, alpha and beta waves and the type and amount of the pathologic EEG patterns were noted during each recording. Differences in cortical localization and the influence of sound stimuli on spontaneous cortical activity were evaluated between the groups. RESULTS: The tinnitus group exhibited decreased delta activity and increased alpha and beta activity. Hyperventilation increased the intensity of the differences. The tinnitus patients had more sharp-slow waves and increased slow wave amplitude. Sound stimuli modified the EEG recordings; the delta and beta wave amplitudes were increased, whereas the alpha-1 wave amplitude was decreased. Acoustic stimulation only slightly affected the temporal region. CONCLUSION: Cortical activity in the tinnitus patients clearly differed from that in healthy subjects, i.e., tinnitus is not a “phantom” sign. The changes in cortical activity included decreased delta wave amplitudes, increased alpha-1, beta-1 and beta-h wave amplitudes and pathologic patterns. Cortical activity modifications occurred predominantly in the temporal region. Acoustic stimulation affected spontaneous cortical activity only in tinnitus patients, and although the applied sound was individually matched, the pathologic changes were only slightly improved.

  20. Altered cortical communication in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Blain-Moraes, Stefanie; Mashour, George A; Lee, Heonsoo; Huggins, Jane E; Lee, Uncheol

    2013-05-24

    Amyotrophic lateral sclerosis (ALS) is a disorder associated primarily with the degeneration of the motor system. More recently, functional connectivity studies have demonstrated potentially adaptive changes in ALS brain organization, but disease-related changes in cortical communication remain unknown. We recruited individuals with ALS and age-matched controls to operate a brain-computer interface while electroencephalography was recorded over three sessions. Using normalized symbolic transfer entropy, we measured directed functional connectivity from frontal to parietal (feedback connectivity) and parietal to frontal (feedforward connectivity) regions. Feedback connectivity was not significantly different between groups, but feedforward connectivity was significantly higher in individuals with ALS. This result was consistent across a broad electroencephalographic spectrum (4-35 Hz), and in theta, alpha and beta frequency bands. Feedback connectivity has been associated with conscious state and was found to be independent of ALS symptom severity in this study, which may have significant implications for the detection of consciousness in individuals with advanced ALS. We suggest that increases in feedforward connectivity represent a compensatory response to the ALS-related loss of input such that sensory stimuli have sufficient strength to cross the threshold necessary for conscious processing in the global neuronal workspace. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Cortico-cortical communication dynamics

    Directory of Open Access Journals (Sweden)

    Per E Roland

    2014-05-01

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

  2. Stroke rehabilitation using noninvasive cortical stimulation: aphasia.

    Science.gov (United States)

    Mylius, Veit; Zouari, Hela G; Ayache, Samar S; Farhat, Wassim H; Lefaucheur, Jean-Pascal

    2012-08-01

    Poststroke aphasia results from the lesion of cortical areas involved in the motor production of speech (Broca's aphasia) or in the semantic aspects of language comprehension (Wernicke's aphasia). Such lesions produce an important reorganization of speech/language-specific brain networks due to an imbalance between cortical facilitation and inhibition. In fact, functional recovery is associated with changes in the excitability of the damaged neural structures and their connections. Two main mechanisms are involved in poststroke aphasia recovery: the recruitment of perilesional regions of the left hemisphere in case of small lesion and the acquisition of language processing ability in homotopic areas of the nondominant right hemisphere when left hemispheric language abilities are permanently lost. There is some evidence that noninvasive cortical stimulation, especially when combined with language therapy or other therapeutic approaches, can promote aphasia recovery. Cortical stimulation was mainly used to either increase perilesional excitability or reduce contralesional activity based on the concept of reciprocal inhibition and maladaptive plasticity. However, recent studies also showed some positive effects of the reinforcement of neural activities in the contralateral right hemisphere, based on the potential compensatory role of the nondominant hemisphere in stroke recovery.

  3. Cortical enhancement in chronic subdural hematoma

    International Nuclear Information System (INIS)

    Taguchi, Yoshio; Sato, Jun; Makita, Tadatoshi; Hayashi, Shigetoshi; Nakamura, Norio.

    1981-01-01

    In the CT findings of chronic subdural hematoma, brain enhancement adjacent to a subdural hematoma was seen occasionally after the injection of a contrast material. The authors called this finding ''cortical enhancement'', and 35 cases of chronic subdural hematoma were studied concerning cortical enhancement in relation to age, clinical signs and symptoms, hematoma density, and volume of the hematoma. Eight cases out of the 35 were subjected to measurements of the regional cerebral blood flow preoperatively by the method of the carotid injection of Xe-133. Cortical enhancement was apt to be seen in the cases which revealed intracranial hypertension or disturbance of consciousness, in isodensity or mixed-density hematomas, and in huge subdural hematomas. There was no specific correlation with age distribution. The pathogenesis of cortical enhancement seemed to be the result of cerebral compression with an increase in the contrast material per unit of volume and a prolonged venous outflow from the hemisphere, but no characteristic feature was detected in the average regional cerebral blood flow in our cases. (author)

  4. Progressive posterior cortical dysfunction

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    Fábio Henrique de Gobbi Porto

    Full Text Available Abstract Progressive posterior cortical dysfunction (PPCD is an insidious syndrome characterized by prominent disorders of higher visual processing. It affects both dorsal (occipito-parietal and ventral (occipito-temporal pathways, disturbing visuospatial processing and visual recognition, respectively. We report a case of a 67-year-old woman presenting with progressive impairment of visual functions. Neurologic examination showed agraphia, alexia, hemispatial neglect (left side visual extinction, complete Balint's syndrome and visual agnosia. Magnetic resonance imaging showed circumscribed atrophy involving the bilateral parieto-occipital regions, slightly more predominant to the right . Our aim was to describe a case of this syndrome, to present a video showing the main abnormalities, and to discuss this unusual presentation of dementia. We believe this article can contribute by improving the recognition of PPCD.

  5. Progressive posterior cortical dysfunction

    Science.gov (United States)

    Porto, Fábio Henrique de Gobbi; Machado, Gislaine Cristina Lopes; Morillo, Lilian Schafirovits; Brucki, Sonia Maria Dozzi

    2010-01-01

    Progressive posterior cortical dysfunction (PPCD) is an insidious syndrome characterized by prominent disorders of higher visual processing. It affects both dorsal (occipito-parietal) and ventral (occipito-temporal) pathways, disturbing visuospatial processing and visual recognition, respectively. We report a case of a 67-year-old woman presenting with progressive impairment of visual functions. Neurologic examination showed agraphia, alexia, hemispatial neglect (left side visual extinction), complete Balint’s syndrome and visual agnosia. Magnetic resonance imaging showed circumscribed atrophy involving the bilateral parieto-occipital regions, slightly more predominant to the right. Our aim was to describe a case of this syndrome, to present a video showing the main abnormalities, and to discuss this unusual presentation of dementia. We believe this article can contribute by improving the recognition of PPCD. PMID:29213665

  6. Modeling cortical circuits.

    Energy Technology Data Exchange (ETDEWEB)

    Rohrer, Brandon Robinson; Rothganger, Fredrick H.; Verzi, Stephen J.; Xavier, Patrick Gordon

    2010-09-01

    The neocortex is perhaps the highest region of the human brain, where audio and visual perception takes place along with many important cognitive functions. An important research goal is to describe the mechanisms implemented by the neocortex. There is an apparent regularity in the structure of the neocortex [Brodmann 1909, Mountcastle 1957] which may help simplify this task. The work reported here addresses the problem of how to describe the putative repeated units ('cortical circuits') in a manner that is easily understood and manipulated, with the long-term goal of developing a mathematical and algorithmic description of their function. The approach is to reduce each algorithm to an enhanced perceptron-like structure and describe its computation using difference equations. We organize this algorithmic processing into larger structures based on physiological observations, and implement key modeling concepts in software which runs on parallel computing hardware.

  7. Role of IGF-1 in cortical plasticity and functional deficit induced by sensorimotor restriction.

    Science.gov (United States)

    Mysoet, Julien; Dupont, Erwan; Bastide, Bruno; Canu, Marie-Hélène

    2015-09-01

    In the adult rat, sensorimotor restriction by hindlimb unloading (HU) is known to induce impairments in motor behavior as well as a disorganization of somatosensory cortex (shrinkage of the cortical representation of the hindpaw, enlargement of the cutaneous receptive fields, decreased cutaneous sensibility threshold). Recently, our team has demonstrated that IGF-1 level was decreased in the somatosensory cortex of rats submitted to a 14-day period of HU. To determine whether IGF-1 is involved in these plastic mechanisms, a chronic cortical infusion of this substance was performed by means of osmotic minipump. When administered in control rats, IGF-1 affects the size of receptive fields and the cutaneous threshold, but has no effect on the somatotopic map. In addition, when injected during the whole HU period, IGF-1 is interestingly implied in cortical changes due to hypoactivity: the shrinkage of somatotopic representation of hindlimb is prevented, whereas the enlargement of receptive fields is reduced. IGF-1 has no effect on the increase in neuronal response to peripheral stimulation. We also explored the functional consequences of IGF-1 level restoration on tactile sensory discrimination. In HU rats, the percentage of paw withdrawal after a light tactile stimulation was decreased, whereas it was similar to control level in HU-IGF-1 rats. Taken together, the data clearly indicate that IGF-1 plays a key-role in cortical plastic mechanisms and in behavioral alterations induced by a decrease in sensorimotor activity. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Altered Regional Brain Cortical Thickness in Pediatric Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Paul M. Macey

    2018-01-01

    Full Text Available RationaleObstructive sleep apnea (OSA affects 2–5% of all children and is associated with cognitive and behavioral deficits, resulting in poor school performance. These psychological deficits may arise from brain injury, as seen in preliminary findings of lower gray matter volume among pediatric OSA patients. However, the psychological deficits in OSA are closely related to functions in the cortex, and such brain areas have not been specifically assessed. The objective was to determine whether cortical thickness, a marker of possible brain injury, is altered in children with OSA.MethodsWe examined regional brain cortical thicknesses using high-resolution T1-weighted magnetic resonance images in 16 pediatric OSA patients (8 males; mean age ± SD = 8.4 ± 1.2 years; mean apnea/hypopnea index ± SD = 11 ± 6 events/h and 138 controls (8.3 ± 1.1 years; 62 male; 138 subjects from the NIH Pediatric MRI database to identify cortical thickness differences in pediatric OSA subjects.ResultsCortical thinning occurred in multiple regions including the superior frontal, ventral medial prefrontal, and superior parietal cortices. The left side showed greater thinning in the superior frontal cortex. Cortical thickening was observed in bilateral precentral gyrus, mid-to-posterior insular cortices, and left central gyrus, as well as right anterior insula cortex.ConclusionChanges in cortical thickness are present in children with OSA and likely indicate disruption to neural developmental processes, including maturational patterns of cortical volume increases and synaptic pruning. Regions with thicker cortices may reflect inflammation or astrocyte activation. Both the thinning and thickening associated with OSA in children may contribute to the cognitive and behavioral dysfunction frequently found in the condition.

  9. Massive cortical reorganization in sighted Braille readers.

    Science.gov (United States)

    Siuda-Krzywicka, Katarzyna; Bola, Łukasz; Paplińska, Małgorzata; Sumera, Ewa; Jednoróg, Katarzyna; Marchewka, Artur; Śliwińska, Magdalena W; Amedi, Amir; Szwed, Marcin

    2016-03-15

    The brain is capable of large-scale reorganization in blindness or after massive injury. Such reorganization crosses the division into separate sensory cortices (visual, somatosensory...). As its result, the visual cortex of the blind becomes active during tactile Braille reading. Although the possibility of such reorganization in the normal, adult brain has been raised, definitive evidence has been lacking. Here, we demonstrate such extensive reorganization in normal, sighted adults who learned Braille while their brain activity was investigated with fMRI and transcranial magnetic stimulation (TMS). Subjects showed enhanced activity for tactile reading in the visual cortex, including the visual word form area (VWFA) that was modulated by their Braille reading speed and strengthened resting-state connectivity between visual and somatosensory cortices. Moreover, TMS disruption of VWFA activity decreased their tactile reading accuracy. Our results indicate that large-scale reorganization is a viable mechanism recruited when learning complex skills.

  10. Early development of synchrony in cortical activations in the human.

    Science.gov (United States)

    Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

    2016-05-13

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Extensive video-game experience alters cortical networks for complex visuomotor transformations.

    Science.gov (United States)

    Granek, Joshua A; Gorbet, Diana J; Sergio, Lauren E

    2010-10-01

    Using event-related functional magnetic resonance imaging (fMRI), we examined the effect of video-game experience on the neural control of increasingly complex visuomotor tasks. Previously, skilled individuals have demonstrated the use of a more efficient movement control brain network, including the prefrontal, premotor, primary sensorimotor and parietal cortices. Our results extend and generalize this finding by documenting additional prefrontal cortex activity in experienced video gamers planning for complex eye-hand coordination tasks that are distinct from actual video-game play. These changes in activation between non-gamers and extensive gamers are putatively related to the increased online control and spatial attention required for complex visually guided reaching. These data suggest that the basic cortical network for processing complex visually guided reaching is altered by extensive video-game play. Crown Copyright © 2009. Published by Elsevier Srl. All rights reserved.

  12. Interactive effects of dehydroepiandrosterone and testosterone on cortical thickness during early brain development.

    Science.gov (United States)

    Nguyen, Tuong-Vi; McCracken, James T; Ducharme, Simon; Cropp, Brett F; Botteron, Kelly N; Evans, Alan C; Karama, Sherif

    2013-06-26

    Humans and the great apes are the only species demonstrated to exhibit adrenarche, a key endocrine event associated with prepubertal increases in the adrenal production of androgens, most significantly dehydroepiandrosterone (DHEA) and to a certain degree testosterone. Adrenarche also coincides with the emergence of the prosocial and neurobehavioral skills of middle childhood and may therefore represent a human-specific stage of development. Both DHEA and testosterone have been reported in animal and in vitro studies to enhance neuronal survival and programmed cell death depending on the timing, dose, and hormonal context involved, and to potentially compete for the same signaling pathways. Yet no extant brain-hormone studies have examined the interaction between DHEA- and testosterone-related cortical maturation in humans. Here, we used linear mixed models to examine changes in cortical thickness associated with salivary DHEA and testosterone levels in a longitudinal sample of developmentally healthy children and adolescents 4-22 years old. DHEA levels were associated with increases in cortical thickness of the left dorsolateral prefrontal cortex, right temporoparietal junction, right premotor and right entorhinal cortex between the ages of 4-13 years, a period marked by the androgenic changes of adrenarche. There was also an interaction between DHEA and testosterone on cortical thickness of the right cingulate cortex and occipital pole that was most significant in prepubertal subjects. DHEA and testosterone appear to interact and modulate the complex process of cortical maturation during middle childhood, consistent with evidence at the molecular level of fast/nongenomic and slow/genomic or conversion-based mechanisms underlying androgen-related brain development.

  13. Tested Demonstrations.

    Science.gov (United States)

    Gilbert, George L.

    1983-01-01

    An apparatus is described in which effects of pressure, volume, and temperature changes on a gas can be observed simultaneously. Includes use of the apparatus in demonstrating Boyle's, Gay-Lussac's, and Charles' Laws, attractive forces, Dalton's Law of Partial pressures, and in illustrating measurable vapor pressures of liquids and some solids.…

  14. Tested Demonstrations.

    Science.gov (United States)

    Gilbert, George L., Ed.

    1987-01-01

    Describes two demonstrations to illustrate characteristics of substances. Outlines a method to detect the changes in pH levels during the electrolysis of water. Uses water pistols, one filled with methane gas and the other filled with water, to illustrate the differences in these two substances. (TW)

  15. Electrophysiological and pathological study of focal cortical dysplasia

    International Nuclear Information System (INIS)

    Hodozuka, Akira; Hashizume, Kiyotaka; Hayashi, Yoshimitsu; Tanaka, Tatsuya

    2008-01-01

    Clinical and experimental studies on focal cortical dysplasia (FCD) were carried out. For the experimental study, an experimental FCD model of rats was developed. Twenty Wistar rats at 0-2 days after birth were used for the study. Kainic acid (KA) solution was injected stereotaxically into medial and lateral sites of the sensori-motor cortex. Bipolar electrodes were inserted. The behavior of the rats and electroencephalography (EEG) were recorded using a digital video-EEG monitoring system. After observation periods of 1, 2 and 6 months, the rats were perfused for pathological study. FCD was observed adjacent to the site of KA injection in all rats more than one month after the injection. EEG recording demonstrated focal spike discharges in and around the site of injection. However, clinical seizure was not observed. Pathological studies showed decrease in gamma aminobutyric acid (GABA)-A receptors and increase in GABA-B receptors not only in the lesion but also in perilesional areas. Fifteen surgical cases of FCD with intractable epilepsy were included in the clinical study. Neuro-imaging studies including high-resolution MRI and single photon emission computed tomography (SPECT) were performed. Conventional EEG studies demonstrated focal EEG abnormalities with epileptic phenomena. At surgery, intraoperative electrocorticography (ECoG) was performed in order to localize epileptic foci under neuroleptanalgesia. Fourteen patients showed epileptiform discharges on preresection ECoG. All foci in non-eloquent areas were resected. Pathological studies including immunohistochemical staining were performed, and characteristics of the FCD in relation to EEG findings were analyzed. Electrophysiological examination revealed epileptogenecity not only in the lesions but also in perilesional areas. In the lesions, immunohistochemical studies showed decrease in GABA-A receptors and increase in GABA-B receptors in both the lesions and perilesional areas, but N

  16. Cortical entrainment to music and its modulation by expertise.

    Science.gov (United States)

    Doelling, Keith B; Poeppel, David

    2015-11-10

    Recent studies establish that cortical oscillations track naturalistic speech in a remarkably faithful way. Here, we test whether such neural activity, particularly low-frequency (music and whether experience modifies such a cortical phenomenon. Music of varying tempi was used to test entrainment at different rates. In three magnetoencephalography experiments, we recorded from nonmusicians, as well as musicians with varying years of experience. Recordings from nonmusicians demonstrate cortical entrainment that tracks musical stimuli over a typical range of tempi, but not at tempi below 1 note per second. Importantly, the observed entrainment correlates with performance on a concurrent pitch-related behavioral task. In contrast, the data from musicians show that entrainment is enhanced by years of musical training, at all presented tempi. This suggests a bidirectional relationship between behavior and cortical entrainment, a phenomenon that has not previously been reported. Additional analyses focus on responses in the beta range (∼15-30 Hz)-often linked to delta activity in the context of temporal predictions. Our findings provide evidence that the role of beta in temporal predictions scales to the complex hierarchical rhythms in natural music and enhances processing of musical content. This study builds on important findings on brainstem plasticity and represents a compelling demonstration that cortical neural entrainment is tightly coupled to both musical training and task performance, further supporting a role for cortical oscillatory activity in music perception and cognition.

  17. Perceptual incongruence influences bistability and cortical activation.

    Directory of Open Access Journals (Sweden)

    Gijs Joost Brouwer

    Full Text Available We employed a parametric psychophysical design in combination with functional imaging to examine the influence of metric changes in perceptual incongruence on perceptual alternation rates and cortical responses. Subjects viewed a bistable stimulus defined by incongruent depth cues; bistability resulted from incongruence between binocular disparity and monocular perspective cues that specify different slants (slant rivalry. Psychophysical results revealed that perceptual alternation rates were positively correlated with the degree of perceived incongruence. Functional imaging revealed systematic increases in activity that paralleled the psychophysical results within anterior intraparietal sulcus, prior to the onset of perceptual alternations. We suggest that this cortical activity predicts the frequency of subsequent alternations, implying a putative causal role for these areas in initiating bistable perception. In contrast, areas implicated in form and depth processing (LOC and V3A were sensitive to the degree of slant, but failed to show increases in activity when these cues were in conflict.

  18. Post-event reviews: Using a quantitative approach for analysing incident response to demonstrate the value of business continuity programmes and increase planning efficiency.

    Science.gov (United States)

    Vaidyanathan, Karthik

    2017-01-01

    Business continuity management is often thought of as a proactive planning process for minimising impact from large-scale incidents and disasters. While this is true, and it is critical to plan for the worst, consistently validating plan effectiveness against smaller disruptions can enable an organisation to gain key insights about its business continuity readiness, drive programme improvements, reduce costs and provide an opportunity to quantitatively demonstrate the value of the programme to management. This paper describes a post mortem framework which is used as a continuous improvement mechanism for tracking, reviewing and learning from real-world events at Microsoft Customer Service & Support. This approach was developed and adopted because conducting regular business continuity exercises proved difficult and expensive in a complex and distributed operations environment with high availability requirements. Using a quantitative approach to measure response to incidents, and categorising outcomes based on such responses, enables business continuity teams to provide data-driven insights to leadership, change perceptions of incident root cause, and instil a higher level of confidence towards disaster response readiness and incident management. The scope of the framework discussed here is specific to reviewing and driving improvements from operational incidents. However, the concept can be extended to learning and evolving readiness plans for other types of incidents.

  19. Flow velocity change in the cortical vein during motor activation and its effect on functional brain MRI

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Kazuhiro [Kyoto Prefectural Univ. of Medicine (Japan)

    1998-06-01

    On the brain functional magnetic resonance imaging (fMRI) using the gradient-recalled echo technique with clinical MR scanner, the activated areas nearly correspond with the cortical veins. This suggests that the fMRI signal mainly originates from the cortical veins. In this study, we analyzed the flow velocity in the cortical vein quantitatively during brain activation and resting status using 2 dimensional time-of-flight cine MR venography (2D-TOF-cine-MRV) and 2 dimensional phase contrast MRV (2D-PC-MRV) techniques, and demonstrated that the flow velocity increased in the cortical vein corresponding to the activated area during activation status. The increase of flow velocity was calculated to be about 20%. The reason for the increased flow velocity is probably due to the increased regional cerebral blood flow and volume in the activated area. We should be careful to analyze the data of the fMRI because the flow velocity affects the fMRI signal such as the inflow effect and the oblique flow effect. When using the gradient echo method, the effect of the flow velocity is one of the important factors of the fMRI signal. (author)

  20. Contrasting nutritional acclimation of sugar maple (Acer saccharum Marsh. and red maple (Acer rubrum L. to increasing conifers and soil acidity as demonstrated by foliar nutrient balances

    Directory of Open Access Journals (Sweden)

    Alexandre Collin

    2016-07-01

    Full Text Available Sugar maple (Acer saccharum Marshall, SM is believed to be more sensitive to acidic and nutrient-poor soils associated with conifer-dominated stands than red maple (Acer rubrum L., RM. Greater foliar nutrient use efficiency (FNUE of RM is likely the cause for this difference. In the context of climate change, this greater FNUE could be key in favouring northward migration of RM over SM. We used the concept of foliar nutrient balances to study the nutrition of SM and RM seedlings along an increasing gradient in forest floor acidity conditioned by increasing proportions of conifers (pH values ranging from 4.39 under hardwoods, to 4.29 under mixed hardwood-conifer stands and 4.05 under conifer-dominated stands. Nutrients were subjected to isometric log-ratio (ilr transformation, which views the leaf as one closed system and considers interactions between nutrients. The ilr method eliminates numerical biases and weak statistical inferences based on raw or operationally’’ log-transformed data. We analyzed foliar nutrients of SM and RM seedlings and found that the [Ca,Mg,K|P,N] and [Ca,Mg|K] balances of SM seedlings were significantly different among soil acidity levels, whereas they did not vary for RM seedlings. For SM seedlings, these differences among soil acidity levels were due to a significant decrease in foliar Ca and Mg concentrations with increasing forest floor acidity. Similar differences in foliar balances were also found between healthy and declining SM stands estimated from literature values. Conversely, foliar balances of RM seedlings did not differ among soil acidity levels, even though untransformed foliar nutrient concentrations were significantly different. This result highlights the importance of using ilr transformation, since it provides more sensitive results than standard testing of untransformed nutrient concentrations. The lower nutrient requirements of RM and its greater capacity to maintain nutrient equilibrium are

  1. Enhancement of synaptic transmission induced by BDNF in cultured cortical neurons

    Science.gov (United States)

    He, Jun; Gong, Hui; Zeng, Shaoqun; Li, Yanling; Luo, Qingming

    2005-03-01

    Brain-derived neurotrophic factor (BDNF), like other neurotrophins, has long-term effects on neuronal survival and differentiation; furthermore, BDNF has been reported to exert an acute potentiation of synaptic activity and are critically involved in long-term potentiation (LTP). We found that BDNF rapidly induced potentiation of synaptic activity and an increase in the intracellular Ca2+ concentration in cultured cortical neurons. Within minutes of BDNF application to cultured cortical neurons, spontaneous firing rate was dramatically increased as were the frequency and amplitude of excitatory spontaneous postsynaptic currents (EPSCs). Fura-2 recordings showed that BDNF acutely elicited an increase in intracellular calcium concentration ([Ca2+]c). This effect was partially dependent on [Ca2+]o; The BDNF-induced increase in [Ca2+]c can not be completely blocked by Ca2+-free solution. It was completely blocked by K252a and partially blocked by Cd2+ and TTX. The results demonstrate that BDNF can enhances synaptic transmission and that this effect is accompanied by a rise in [Ca2+]c that requires two route: the release of Ca2+ from intracellular calcium stores and influx of extracellular Ca2+ through voltage-dependent Ca2+ channels in cultured cortical neurons.

  2. Classification of Cortical Brain Malformations

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-03-01

    Full Text Available Clinical, radiological, and genetic classifications of 113 cases of malformations of cortical development (MCD were evaluated at the Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.

  3. Extensive cortical rewiring after brain injury.

    Science.gov (United States)

    Dancause, Numa; Barbay, Scott; Frost, Shawn B; Plautz, Erik J; Chen, Daofen; Zoubina, Elena V; Stowe, Ann M; Nudo, Randolph J

    2005-11-02

    Previously, we showed that the ventral premotor cortex (PMv) underwent neurophysiological remodeling after injury to the primary motor cortex (M1). In the present study, we examined cortical connections of PMv after such lesions. The neuroanatomical tract tracer biotinylated dextran amine was injected into the PMv hand area at least 5 months after ischemic injury to the M1 hand area. Comparison of labeling patterns between experimental and control animals demonstrated extensive proliferation of novel PMv terminal fields and the appearance of retrogradely labeled cell bodies within area 1/2 of the primary somatosensory cortex after M1 injury. Furthermore, evidence was found for alterations in the trajectory of PMv intracortical axons near the site of the lesion. The results suggest that M1 injury results in axonal sprouting near the ischemic injury and the establishment of novel connections within a distant target. These results support the hypothesis that, after a cortical injury, such as occurs after stroke, cortical areas distant from the injury undergo major neuroanatomical reorganization. Our results reveal an extraordinary anatomical rewiring capacity in the adult CNS after injury that may potentially play a role in recovery.

  4. Spatial integration and cortical dynamics.

    Science.gov (United States)

    Gilbert, C D; Das, A; Ito, M; Kapadia, M; Westheimer, G

    1996-01-23

    Cells in adult primary visual cortex are capable of integrating information over much larger portions of the visual field than was originally thought. Moreover, their receptive field properties can be altered by the context within which local features are presented and by changes in visual experience. The substrate for both spatial integration and cortical plasticity is likely to be found in a plexus of long-range horizontal connections, formed by cortical pyramidal cells, which link cells within each cortical area over distances of 6-8 mm. The relationship between horizontal connections and cortical functional architecture suggests a role in visual segmentation and spatial integration. The distribution of lateral interactions within striate cortex was visualized with optical recording, and their functional consequences were explored by using comparable stimuli in human psychophysical experiments and in recordings from alert monkeys. They may represent the substrate for perceptual phenomena such as illusory contours, surface fill-in, and contour saliency. The dynamic nature of receptive field properties and cortical architecture has been seen over time scales ranging from seconds to months. One can induce a remapping of the topography of visual cortex by making focal binocular retinal lesions. Shorter-term plasticity of cortical receptive fields was observed following brief periods of visual stimulation. The mechanisms involved entailed, for the short-term changes, altering the effectiveness of existing cortical connections, and for the long-term changes, sprouting of axon collaterals and synaptogenesis. The mutability of cortical function implies a continual process of calibration and normalization of the perception of visual attributes that is dependent on sensory experience throughout adulthood and might further represent the mechanism of perceptual learning.

  5. Spatial integration and cortical dynamics.

    OpenAIRE

    Gilbert, C D; Das, A; Ito, M; Kapadia, M; Westheimer, G

    1996-01-01

    Cells in adult primary visual cortex are capable of integrating information over much larger portions of the visual field than was originally thought. Moreover, their receptive field properties can be altered by the context within which local features are presented and by changes in visual experience. The substrate for both spatial integration and cortical plasticity is likely to be found in a plexus of long-range horizontal connections, formed by cortical pyramidal cells, which link cells wi...

  6. Motor cortical plasticity in Parkinson's disease.

    Science.gov (United States)

    Udupa, Kaviraja; Chen, Robert

    2013-09-04

    In Parkinson's disease (PD), there are alterations of the basal ganglia (BG) thalamocortical networks, primarily due to degeneration of nigrostriatal dopaminergic neurons. These changes in subcortical networks lead to plastic changes in primary motor cortex (M1), which mediates cortical motor output and is a potential target for treatment of PD. Studies investigating the motor cortical plasticity using non-invasive transcranial magnetic stimulation (TMS) have found altered plasticity in PD, but there are inconsistencies among these studies. This is likely because plasticity depends on many factors such as the extent of dopaminergic loss and disease severity, response to dopaminergic replacement therapies, development of l-DOPA-induced dyskinesias (LID), the plasticity protocol used, medication, and stimulation status in patients treated with deep brain stimulation (DBS). The influences of LID and DBS on BG and M1 plasticity have been explored in animal models and in PD patients. In addition, many other factors such age, genetic factors (e.g., brain derived neurotropic factor and other neurotransmitters or receptors polymorphism), emotional state, time of the day, physical fitness have been documented to play role in the extent of plasticity induced by TMS in human studies. In this review, we summarize the studies that investigated M1 plasticity in PD and demonstrate how these afore-mentioned factors affect motor cortical plasticity in PD. We conclude that it is important to consider the clinical, demographic, and technical factors that influence various plasticity protocols while developing these protocols as diagnostic or prognostic tools in PD. We also discuss how the modulation of cortical excitability and the plasticity with these non-invasive brain stimulation techniques facilitate the understanding of the pathophysiology of PD and help design potential therapeutic possibilities in this disorder.

  7. Technical development to increase the use of reed canary grass - Full scale demonstration; Teknikutveckling foer oekad etablering och nyttjande av roerflen - Demonstrationsfoersoek i fullskala

    Energy Technology Data Exchange (ETDEWEB)

    Oerberg, Haakan; Skoglund, Nils; Grimm, Alejandro; Bostroem, Dan; Oehman, Marcus

    2010-06-15

    characterization of fly ashes from electric filter and bed material does not show any changes in chemical composition. Thus from these test it can be concluded that mixing in 10% RCG on energy base has no negative influence of combustion process in a CFB boiler. Two tests were done with briquettes made of RCG and peat, one in Eskilstuna 4MW grate fired boiler and one in Roebaecksdalen 600 kW grate fired boiler. The RCG was produced on organic soil to obtain low ash content. Comparisons were made between briquettes made with 100% RCG (high ash content) and with briquettes with 15% peat on weight base mixed with 85% RCG with low ash content. Results from these combustion tests show that NO{sub x} emissions increased when RCG was used compared to wood pellets (600 kW boiler) explained by high N content in RCG. Even the total dust in flue gas increased with RCG compared with wood pellets (600 kW boiler) but total dust emissions were reduced with 50% when peat was mixed in briquettes.

  8. Hiperostosis cortical infantil

    Directory of Open Access Journals (Sweden)

    Salvador Javier Santos Medina

    2015-04-01

    Full Text Available La enfermedad de Caffey, o hiperostosis cortical infantil, es una rara enfermedad ósea autolimitada, que aparece de preferencia en lactantes con signos inespecíficos sistémicos; el más relevante es la reacción subperióstica e hiperostosis en varios huesos del cuerpo, con predilección en el 75-80 % de los casos por la mandíbula. Su pronóstico es bueno, la mayoría no deja secuelas. El propósito del presente trabajo es describir las características clínicas, presentes en un lactante de cinco meses de edad, atendido en el Hospital Pediátrico Provincial “Mártires de Las Tunas” con este diagnóstico, quien ingresó en el servicio de miscelánea B por una celulitis facial. Presentaba aumento de volumen en la región geniana izquierda, febrícola e inapetencia. Se impuso tratamiento con cefazolina y se egresó a los siete días. Acudió nuevamente con tumefacción blanda y difusa de ambas hemicaras, irritabilidad y fiebre. Se interconsultó con cirugía maxilofacial, se indicaron estudios sanguíneos y radiológicos. Se diagnosticó como enfermedad de Caffey, basado en la edad del niño, tumefacción facial sin signos inflamatorios agudos e hiperostosis en ambas corticales mandibulares a la radiografía AP mandíbula; unido a anemia ligera, leucocitosis y eritrosedimentación acelerada. El paciente se trató sintomáticamente y con antinflamatorios no esteroideos. Esta rara entidad se debe tener presente en casos de niños y lactantes con irritabilidad y fiebre inespecífica

  9. Transcranial magnetic stimulation reveals cortical hyperexcitability in episodic cluster headache.

    Science.gov (United States)

    Cosentino, Guiseppe; Brighina, Filippo; Brancato, Sara; Valentino, Francesca; Indovino, Serena; Fierro, Brigida

    2015-01-01

    Evidence shows involvement of the cerebral cortex in the pathophysiology of cluster headache (CH). Here we investigated cortical excitability in episodic CH patients by using transcranial magnetic stimulation. In 25 patients with episodic CH and 13 healthy subjects we evaluated the motor cortical response to single-pulse (ie, motor threshold, input-output curves, cortical silent period) and paired-pulse (ie, intracortical facilitation, short intracortical inhibition) transcranial magnetic stimulation in both hemispheres. Thirteen patients were evaluated outside bout and the remaining 12 patients inside bout. Our results showed increased slope of the input-output curves after stimulation of both hemispheres in patients outside bout and in the hemisphere contralateral to the headache side in patients inside bout. Increased intracortical facilitation was observed in the hemisphere ipsilateral to the headache side in patients evaluated both outside and inside bout; reduced short intracortical inhibition was observed in patients inside bout ipsilateral to the side of pain. In conclusion, we provide evidence of increased cortical excitability in episodic CH both outside and inside bout, especially in the hemisphere ipsilateral to the side of headache attacks. Our results suggest that an abnormal regulation of cortical excitability could be involved in the pathophysiology of CH. We investigated cortical excitability in episodic cluster headache by using transcranial magnetic stimulation, providing evidence of cortical hyperexcitability in patients both inside and outside bout. We suggest that an abnormal state of cortical excitability could be involved in the pathophysiology of the disease. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  10. Prenatal programming of rat cortical collecting tubule sodium transport.

    Science.gov (United States)

    Cheng, Chih-Jen; Lozano, German; Baum, Michel

    2012-03-15

    Prenatal insults have been shown to lead to elevated blood pressure in offspring when they are studied as adults. Prenatal administration of dexamethasone and dietary protein deprivation have demonstrated that there is an increase in transporter abundance for a number of nephron segments but not the subunits of the epithelial sodium channel (ENaC) in the cortical collecting duct. Recent studies have shown that aldosterone is elevated in offspring of protein-deprived mothers when studied as adults, but the physiological importance of the increase in serum aldosterone is unknown. As an indirect measure of ENaC activity, we compared the natriuretic response to benzamil in offspring of mothers who ate a low-protein diet (6%) with those who ate a normal diet (20%) for the last half of pregnancy. The natriuretic response to benzamil was greater in the 6% group (821.1 ± 161.0 μmol/24 h) compared with the 20% group (279.1 ± 137.0 μmol/24 h), consistent with greater ENaC activity in vivo (P sodium transport (-1.9 ± 3.1 pmol·mm(-1)·min(-1)), the offspring of rats that ate a 6% protein diet during the last half of pregnancy had a net sodium flux of 10.7 ± 2.6 pmol·mm(-1)·min(-1) (P = 0.01) in tubules perfused in vitro. Sodium transport was measured using ion-selective electrodes, a novel technique allowing measurement of sodium in nanoliter quantities of fluid. Thus we directly demonstrate that there is prenatal programming of cortical collecting duct sodium transport.

  11. MicroRNA-338 modulates cortical neuronal placement and polarity.

    Science.gov (United States)

    Kos, Aron; de Mooij-Malsen, Annetrude J; van Bokhoven, Hans; Kaplan, Barry B; Martens, Gerard J; Kolk, Sharon M; Aschrafi, Armaz

    2017-07-03

    The precise spatial and temporal regulation of gene expression orchestrates the many intricate processes during brain development. In the present study we examined the role of the brain-enriched microRNA-338 (miR-338) during mouse cortical development. Reduction of miR-338 levels in the developing mouse cortex, using a sequence-specific miR-sponge, resulted in a loss of neuronal polarity in the cortical plate and significantly reduced the number of neurons within this cortical layer. Conversely, miR-338 overexpression in developing mouse cortex increased the number of neurons, which exhibited a multipolar morphology. All together, our results raise the possibility for a direct role for this non-coding RNA, which was recently associated with schizophrenia, in the regulation of cortical neuronal polarity and layer placement.

  12. The cortical signature of amyotrophic lateral sclerosis.

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    Federica Agosta

    Full Text Available The aim of this study was to explore the pattern of regional cortical thickness in patients with non-familial amyotrophic lateral sclerosis (ALS and to investigate whether cortical thinning is associated with disease progression rate. Cortical thickness analysis was performed in 44 ALS patients and 26 healthy controls. Group differences in cortical thickness and the age-by-group effects were assessed using vertex-by-vertex and multivariate linear models. The discriminatory ability of MRI variables in distinguishing patients from controls was estimated using the Concordance Statistics (C-statistic within logistic regression analyses. Correlations between cortical thickness measures and disease progression rate were tested using the Pearson coefficient. Relative to controls, ALS patients showed a bilateral cortical thinning of the primary motor, prefrontal and ventral frontal cortices, cingulate gyrus, insula, superior and inferior temporal and parietal regions, and medial and lateral occipital areas. There was a significant age-by-group effect in the sensorimotor cortices bilaterally, suggesting a stronger association between age and cortical thinning in ALS patients compared to controls. The mean cortical thickness of the sensorimotor cortices distinguished patients with ALS from controls (C-statistic ≥ 0.74. Cortical thinning of the left sensorimotor cortices was related to a faster clinical progression (r = -0.33, p = 0.03. Cortical thickness measurements allowed the detection and quantification of motor and extramotor involvement in patients with ALS. Cortical thinning of the precentral gyrus might offer a marker of upper motor neuron involvement and disease progression.

  13. The cortical signature of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Agosta, Federica; Valsasina, Paola; Riva, Nilo; Copetti, Massimiliano; Messina, Maria Josè; Prelle, Alessandro; Comi, Giancarlo; Filippi, Massimo

    2012-01-01

    The aim of this study was to explore the pattern of regional cortical thickness in patients with non-familial amyotrophic lateral sclerosis (ALS) and to investigate whether cortical thinning is associated with disease progression rate. Cortical thickness analysis was performed in 44 ALS patients and 26 healthy controls. Group differences in cortical thickness and the age-by-group effects were assessed using vertex-by-vertex and multivariate linear models. The discriminatory ability of MRI variables in distinguishing patients from controls was estimated using the Concordance Statistics (C-statistic) within logistic regression analyses. Correlations between cortical thickness measures and disease progression rate were tested using the Pearson coefficient. Relative to controls, ALS patients showed a bilateral cortical thinning of the primary motor, prefrontal and ventral frontal cortices, cingulate gyrus, insula, superior and inferior temporal and parietal regions, and medial and lateral occipital areas. There was a significant age-by-group effect in the sensorimotor cortices bilaterally, suggesting a stronger association between age and cortical thinning in ALS patients compared to controls. The mean cortical thickness of the sensorimotor cortices distinguished patients with ALS from controls (C-statistic ≥ 0.74). Cortical thinning of the left sensorimotor cortices was related to a faster clinical progression (r = -0.33, p = 0.03). Cortical thickness measurements allowed the detection and quantification of motor and extramotor involvement in patients with ALS. Cortical thinning of the precentral gyrus might offer a marker of upper motor neuron involvement and disease progression.

  14. Cisternography contribution in the cortical atrophy diagnosis

    International Nuclear Information System (INIS)

    Calegaro, J.U.M.; Balallai, N.; Suzuki, K.

    1975-01-01

    A 37 years-old woman suffered a car accident. On admission to hospital she presented: torpor, the right pupil greater than the left, both reacting to light, and left hemiparesis with homologous Babinski reflex. She was submitted to carotid arteriogram an air-contrast study without significant findings. Eletroencephalographic examination showed diffuse parenquimatous involvement of left cerebral hemisphery. Scinticisternography demonstrated delayed reabsorption of the radioactive tracer in both frontal areas. A subsequent trepanation made the diagnosis of cortical atrophy in the areas mentioned above. This case shows aditional information concerning anatomic detail provided by isotope cisternography, that eventually can't be detected by air-contrast study [pt

  15. Cisternography contribution in the cortical atrophy diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Calegaro, J U.M. [Centro de Analises Clinicas e Medicina Nuclear, Londrina (Brazil); Balallai, N; Suzuki, K [Instituto de Neurologia e Neurocirurgia, Londrina (Brazil)

    1975-01-01

    A 37 years-old woman suffered a car accident. On admission to hospital she presented: torpor, the right pupil greater than the left, both reacting to light, and left hemiparesis with homologous Babinski reflex. She was submitted to carotid arteriogram an air-contrast study without significant findings. Eletroencephalographic examination showed diffuse parenquimatous involvement of left cerebral hemisphery. Scinticisternography demonstrated delayed reabsorption of the radioactive tracer in both frontal areas. A subsequent trepanation made the diagnosis of cortical atrophy in the areas mentioned above. This case shows aditional information concerning anatomic detail provided by isotope cisternography, that eventually can't be detected by air-contrast study.

  16. Evidence for a cerebral cortical thickness network anti-correlated with amygdalar volume in healthy youths: implications for the neural substrates of emotion regulation.

    Science.gov (United States)

    Albaugh, Matthew D; Ducharme, Simon; Collins, D Louis; Botteron, Kelly N; Althoff, Robert R; Evans, Alan C; Karama, Sherif; Hudziak, James J

    2013-05-01

    Recent functional connectivity studies have demonstrated that, in resting humans, activity in a dorsally-situated neocortical network is inversely associated with activity in the amygdalae. Similarly, in human neuroimaging studies, aspects of emotion regulation have been associated with increased activity in dorsolateral, dorsomedial, orbital and ventromedial prefrontal regions, as well as concomitant decreases in amygdalar activity. These findings indicate the presence of two countervailing systems in the human brain that are reciprocally related: a dorsally-situated cognitive control network, and a ventrally-situated limbic network. We investigated the extent to which this functional reciprocity between limbic and dorsal neocortical regions is recapitulated from a purely structural standpoint. Specifically, we hypothesized that amygdalar volume would be related to cerebral cortical thickness in cortical regions implicated in aspects of emotion regulation. In 297 typically developing youths (162 females, 135 males; 572 MRIs), the relationship between cortical thickness and amygdalar volume was characterized. Amygdalar volume was found to be inversely associated with thickness in bilateral dorsolateral and dorsomedial prefrontal, inferior parietal, as well as bilateral orbital and ventromedial prefrontal cortices. Our findings are in line with previous work demonstrating that a predominantly dorsally-centered neocortical network is reciprocally related to core limbic structures such as the amygdalae. Future research may benefit from investigating the extent to which such cortical-limbic morphometric relations are qualified by the presence of mood and anxiety psychopathology. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Cortical tremor: a variant of cortical reflex myoclonus.

    Science.gov (United States)

    Ikeda, A; Kakigi, R; Funai, N; Neshige, R; Kuroda, Y; Shibasaki, H

    1990-10-01

    Two patients with action tremor that was thought to originate in the cerebral cortex showed fine shivering-like finger twitching provoked mainly by action and posture. Surface EMG showed relatively rhythmic discharge at a rate of about 9 Hz, which resembled essential tremor. However, electrophysiologic studies revealed giant somatosensory evoked potentials (SEPs) with enhanced long-loop reflex and premovement cortical spike by the jerk-locked averaging method. Treatment with beta-blocker showed no effect, but anticonvulsants such as clonazepam, valproate, and primidone were effective to suppress the tremor and the amplitude of SEPs. We call this involuntary movement "cortical tremor," which is in fact a variant of cortical reflex myoclonus.

  18. Canonical cortical circuits: current evidence and theoretical implications

    Directory of Open Access Journals (Sweden)

    Capone F

    2016-04-01

    Full Text Available Fioravante Capone,1,2 Matteo Paolucci,1,2 Federica Assenza,1,2 Nicoletta Brunelli,1,2 Lorenzo Ricci,1,2 Lucia Florio,1,2 Vincenzo Di Lazzaro1,2 1Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy; 2Fondazione Alberto Sordi – Research Institute for Aging, Rome, ItalyAbstract: Neurophysiological and neuroanatomical studies have found that the same basic structural and functional organization of neuronal circuits exists throughout the cortex. This kind of cortical organization, termed canonical circuit, has been functionally demonstrated primarily by studies involving visual striate cortex, and then, the concept has been extended to different cortical areas. In brief, the canonical circuit is composed of superficial pyramidal neurons of layers II/III receiving different inputs and deep pyramidal neurons of layer V that are responsible for cortex output. Superficial and deep pyramidal neurons are reciprocally connected, and inhibitory interneurons participate in modulating the activity of the circuit. The main intuition of this model is that the entire cortical network could be modeled as the repetition of relatively simple modules composed of relatively few types of excitatory and inhibitory, highly interconnected neurons. We will review the origin and the application of the canonical cortical circuit model in the six sections of this paper. The first section (The origins of the concept of canonical circuit: the cat visual cortex reviews the experiments performed in the cat visual cortex, from the origin of the concept of canonical circuit to the most recent developments in the modelization of cortex. The second (The canonical circuit in neocortex and third (Toward a canonical circuit in agranular cortex sections try to extend the concept of canonical circuit to other cortical areas, providing some significant examples of circuit functioning in different cytoarchitectonic

  19. Retinoic acid from the meninges regulates cortical neuron generation.

    Science.gov (United States)

    Siegenthaler, Julie A; Ashique, Amir M; Zarbalis, Konstantinos; Patterson, Katelin P; Hecht, Jonathan H; Kane, Maureen A; Folias, Alexandra E; Choe, Youngshik; May, Scott R; Kume, Tsutomu; Napoli, Joseph L; Peterson, Andrew S; Pleasure, Samuel J

    2009-10-30

    Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with the adjacent radial glial endfeet and influence cortical development. We took advantage of Foxc1 mutant mice with defects in forebrain meningeal formation. Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition, Rdh10- and Raldh2-expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants, and Rdh10 mutants had a cortical phenotype similar to the Foxc1 null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis.

  20. Cortically-controlled population stochastic facilitation as a plausible substrate for guiding sensory transfer across the thalamic gateway.

    Directory of Open Access Journals (Sweden)

    Sébastien Béhuret

    Full Text Available The thalamus is the primary gateway that relays sensory information to the cerebral cortex. While a single recipient cortical cell receives the convergence of many principal relay cells of the thalamus, each thalamic cell in turn integrates a dense and distributed synaptic feedback from the cortex. During sensory processing, the influence of this functional loop remains largely ignored. Using dynamic-clamp techniques in thalamic slices in vitro, we combined theoretical and experimental approaches to implement a realistic hybrid retino-thalamo-cortical pathway mixing biological cells and simulated circuits. The synaptic bombardment of cortical origin was mimicked through the injection of a stochastic mixture of excitatory and inhibitory conductances, resulting in a gradable correlation level of afferent activity shared by thalamic cells. The study of the impact of the simulated cortical input on the global retinocortical signal transfer efficiency revealed a novel control mechanism resulting from the collective resonance of all thalamic relay neurons. We show here that the transfer efficiency of sensory input transmission depends on three key features: i the number of thalamocortical cells involved in the many-to-one convergence from thalamus to cortex, ii the statistics of the corticothalamic synaptic bombardment and iii the level of correlation imposed between converging thalamic relay cells. In particular, our results demonstrate counterintuitively that the retinocortical signal transfer efficiency increases when the level of correlation across thalamic cells decreases. This suggests that the transfer efficiency of relay cells could be selectively amplified when they become simultaneously desynchronized by the cortical feedback. When applied to the intact brain, this network regulation mechanism could direct an attentional focus to specific thalamic subassemblies and select the appropriate input lines to the cortex according to the descending

  1. An optimized process flow for rapid segmentation of cortical bones of the craniofacial skeleton using the level-set method.

    Science.gov (United States)

    Szwedowski, T D; Fialkov, J; Pakdel, A; Whyne, C M

    2013-01-01

    Accurate representation of skeletal structures is essential for quantifying structural integrity, for developing accurate models, for improving patient-specific implant design and in image-guided surgery applications. The complex morphology of thin cortical structures of the craniofacial skeleton (CFS) represents a significant challenge with respect to accurate bony segmentation. This technical study presents optimized processing steps to segment the three-dimensional (3D) geometry of thin cortical bone structures from CT images. In this procedure, anoisotropic filtering and a connected components scheme were utilized to isolate and enhance the internal boundaries between craniofacial cortical and trabecular bone. Subsequently, the shell-like nature of cortical bone was exploited using boundary-tracking level-set methods with optimized parameters determined from large-scale sensitivity analysis. The process was applied to clinical CT images acquired from two cadaveric CFSs. The accuracy of the automated segmentations was determined based on their volumetric concurrencies with visually optimized manual segmentations, without statistical appraisal. The full CFSs demonstrated volumetric concurrencies of 0.904 and 0.719; accuracy increased to concurrencies of 0.936 and 0.846 when considering only the maxillary region. The highly automated approach presented here is able to segment the cortical shell and trabecular boundaries of the CFS in clinical CT images. The results indicate that initial scan resolution and cortical-trabecular bone contrast may impact performance. Future application of these steps to larger data sets will enable the determination of the method's sensitivity to differences in image quality and CFS morphology.

  2. Curved planar reconstruction of MR images in focal cortical dysplasia of the brain

    International Nuclear Information System (INIS)

    Chung, Gyung Ho; Lee, Sang Yong; Kim, Chong So; Kim, Young Kon; Lee, Young Hwan; Jeong, Su Hyun

    2002-01-01

    To describe curved planar reconstruction imaging (CPR) and determine its usefulness in the evaluation of focal cortical dysplasia of the brain. In 17 cases of focal cortical dysplasia (cortical dysplasia (n=9), schizencephaly (n=5), and heterotopia (n=3), CPR images were created using a multiplanar reconstruction program and imaging data obtained during T1 magnetization prepared rapid acquisition gradient-echo MR imaging. We assessed the precise configuration of abnormalities and their relation to adjacent gyri and sulci. CPRI showed the brain cortex as a 2D panoramic image, demonstrating the precise configurations and locations of dysplasia-associated abnormalities and their relation to adjacent gyri and sulci, and the precise shape of the gray-white matter interface. CPRI can provide important radiological information about the extension and configuration of focal cortical dysplasia, and its relation to neighboring cortical structures. We believe that CPRI should form an essential part of the routine investigation os suspected cases of focal cortical dysplasia

  3. Alterations of whole-brain cortical area and thickness in mild cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Li, Chuanming; Wang, Jian; Gui, Li; Zheng, Jian; Liu, Chen; Du, Hanjian

    2011-01-01

    Gray matter volume and density of several brain regions, determined by magnetic resonance imaging (MRI), are decreased in Alzheimer's disease (AD). Animal studies have indicated that changes in cortical area size is relevant to thinking and behavior, but alterations of cortical area and thickness in the brains of individuals with AD or its likely precursor, mild cognitive impairment (MCI), have not been reported. In this study, 25 MCI subjects, 30 AD subjects, and 30 age-matched normal controls were recruited for brain MRI scans and Functional Activities Questionnaire (FAQ) assessments. Based on the model using FreeSurfer software, two brain lobes were divided into various regions according to the Desikan-Killiany atlas and the cortical area and thickness of every region was compared and analyzed. We found a significant increase in cortical area of several regions in the frontal and temporal cortices, which correlated negatively with MMSE scores, and a significant decrease in cortical area of several regions in the parietal cortex and the cingulate gyrus in AD subjects. Increased cortical area was also seen in some regions of the frontal and temporal cortices in MCI subjects, whereas the cortical thickness of the same regions was decreased. Our observations suggest characteristic differences of the cortical area and thickness in MCI, AD, and normal control subjects, and these changes may help diagnose both MCI and AD.

  4. Horizontal integration and cortical dynamics.

    Science.gov (United States)

    Gilbert, C D

    1992-07-01

    We have discussed several results that lead to a view that cells in the visual system are endowed with dynamic properties, influenced by context, expectation, and long-term modifications of the cortical network. These observations will be important for understanding how neuronal ensembles produce a system that perceives, remembers, and adapts to injury. The advantage to being able to observe changes at early stages in a sensory pathway is that one may be able to understand the way in which neuronal ensembles encode and represent images at the level of their receptive field properties, of cortical topographies, and of the patterns of connections between cells participating in a network.

  5. A PKC-dependent recruitment of MMP-2 controls semaphorin-3A growth-promoting effect in cortical dendrites.

    Directory of Open Access Journals (Sweden)

    Bertrand Gonthier

    Full Text Available There is increasing evidence for a crucial role of proteases and metalloproteinases during axon growth and guidance. In this context, we recently described a functional link between the chemoattractive Sema3C and Matrix metalloproteinase 3 (MMP3. Here, we provide data demonstrating the involvement of MMP-2 to trigger the growth-promoting effect of Sema3A in cortical dendrites. The in situ analysis of MMP-2 expression and activity is consistent with a functional growth assay demonstrating in vitro that the pharmacological inhibition of MMP-2 reduces the growth of cortical dendrites in response to Sema3A. Hence, our results suggest that the selective recruitment and activation of MMP-2 in response to Sema3A requires a PKC alpha dependent mechanism. Altogether, we provide a second set of data supporting MMPs as effectors of the growth-promoting effects of semaphorins, and we identify the potential signalling pathway involved.

  6. Regional vulnerability of longitudinal cortical association connectivity

    Directory of Open Access Journals (Sweden)

    Rafael Ceschin

    2015-01-01

    Full Text Available Preterm born children with spastic diplegia type of cerebral palsy and white matter injury or periventricular leukomalacia (PVL, are known to have motor, visual and cognitive impairments. Most diffusion tensor imaging (DTI studies performed in this group have demonstrated widespread abnormalities using averaged deterministic tractography and voxel-based DTI measurements. Little is known about structural network correlates of white matter topography and reorganization in preterm cerebral palsy, despite the availability of new therapies and the need for brain imaging biomarkers. Here, we combined novel post-processing methodology of probabilistic tractography data in this preterm cohort to improve spatial and regional delineation of longitudinal cortical association tract abnormalities using an along-tract approach, and compared these data to structural DTI cortical network topology analysis. DTI images were acquired on 16 preterm children with cerebral palsy (mean age 5.6 ± 4 and 75 healthy controls (mean age 5.7 ± 3.4. Despite mean tract analysis, Tract-Based Spatial Statistics (TBSS and voxel-based morphometry (VBM demonstrating diffusely reduced fractional anisotropy (FA reduction in all white matter tracts, the along-tract analysis improved the detection of regional tract vulnerability. The along-tract map-structural network topology correlates revealed two associations: (1 reduced regional posterior–anterior gradient in FA of the longitudinal visual cortical association tracts (inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, optic radiation, posterior thalamic radiation correlated with reduced posterior–anterior gradient of intra-regional (nodal efficiency metrics with relative sparing of frontal and temporal regions; and (2 reduced regional FA within frontal–thalamic–striatal white matter pathways (anterior limb/anterior thalamic radiation, superior longitudinal fasciculus and cortical spinal tract

  7. Effect of superfused insulin on cerebral cortical glucose utilization in awake goats

    International Nuclear Information System (INIS)

    Pelligrino, D.A.; Miletich, D.J.; Albrecht, R.F.

    1987-01-01

    The effect on cortical cerebral glucose utilization (CMR glu ) of intracerebral insulin administration in awake goats was studied. The insulin was superfused in a mock cerebrospinal fluid (CSF) employing chronically implanted cranial windows. Two windows were implanted bilaterally: one window over an equivalent portion of each parietal cortex. With one window used to deliver insulin/CSF and the other used to simultaneously deliver CSF alone (control), changes in CMR glu were assessed using a modification of a sequential 2-[ 3 H]- then 2[ 14 C]deoxy-D-glucose (2DG) technique originally described by Altenau and Agranoff. Initial experiments employing 125 I-insulin demonstrated that the superfusion procedure increased insulin levels only in the outer 1 mm of cortical tissue exposed to insulin containing perfusate. Additional preliminary evaluations, using conditions known to alter CMR glu , generally established that present methods were adequate to induce and detect CMR glu changes. However, it was also shown experimentally and using a mathematical model that 2-[ 3 H]DG test/control tissue ratios could be influenced by subsequent changes in CMR glu and the dephosphorylation rate. Thus 3 H ratios could not be used to establish preexperimental test/control CMR glu relationships as the originally devised model assumed but could be employed to indicate changes in dephosphorylation. The mathematical model allowed for improved estimates of CMR glu changes from 2[ 14 C]DG/2-[ 3 H]DG test over control tissue ratios. Even with these corrections, insulin was estimated to cause no more than an 8-15% increase in cortical CMR glu . A very limited role for insulin, at least in cerebral cortical metabolic regulation, is thus indicated

  8. K -shell decomposition reveals hierarchical cortical organization of the human brain

    International Nuclear Information System (INIS)

    Lahav, Nir; Ksherim, Baruch; Havlin, Shlomo; Ben-Simon, Eti; Maron-Katz, Adi; Cohen, Reuven

    2016-01-01

    In recent years numerous attempts to understand the human brain were undertaken from a network point of view. A network framework takes into account the relationships between the different parts of the system and enables to examine how global and complex functions might emerge from network topology. Previous work revealed that the human brain features ‘small world’ characteristics and that cortical hubs tend to interconnect among themselves. However, in order to fully understand the topological structure of hubs, and how their profile reflect the brain’s global functional organization, one needs to go beyond the properties of a specific hub and examine the various structural layers that make up the network. To address this topic further, we applied an analysis known in statistical physics and network theory as k-shell decomposition analysis. The analysis was applied on a human cortical network, derived from MRI/DSI data of six participants. Such analysis enables us to portray a detailed account of cortical connectivity focusing on different neighborhoods of inter-connected layers across the cortex. Our findings reveal that the human cortex is highly connected and efficient, and unlike the internet network contains no isolated nodes. The cortical network is comprised of a nucleus alongside shells of increasing connectivity that formed one connected giant component, revealing the human brain’s global functional organization. All these components were further categorized into three hierarchies in accordance with their connectivity profile, with each hierarchy reflecting different functional roles. Such a model may explain an efficient flow of information from the lowest hierarchy to the highest one, with each step enabling increased data integration. At the top, the highest hierarchy (the nucleus) serves as a global interconnected collective and demonstrates high correlation with consciousness related regions, suggesting that the nucleus might serve as a

  9. Critical fluctuations in cortical models near instability

    Directory of Open Access Journals (Sweden)

    Matthew J. Aburn

    2012-08-01

    Full Text Available Computational studies often proceed from the premise that cortical dynamics operate in a linearly stable domain, where fluctuations dissipate quickly and show only short memory. Studies of human EEG, however, have shown significant autocorrelation at time lags on the scale of minutes, indicating the need to consider regimes where nonlinearities influence the dynamics. Statistical properties such as increased autocorrelation length, increased variance, power-law scaling and bistable switching have been suggested as generic indicators of the approach to bifurcation in nonlinear dynamical systems. We study temporal fluctuations in a widely-employed computational model (the Jansen-Rit model of cortical activity, examining the statistical signatures that accompany bifurcations. Approaching supercritical Hopf bifurcations through tuning of the background excitatory input, we find a dramatic increase in the autocorrelation length that depends sensitively on the direction in phase space of the input fluctuations and hence on which neuronal subpopulation is stochastically perturbed. Similar dependence on the input direction is found in the distribution of fluctuation size and duration, which show power law scaling that extends over four orders of magnitude at the Hopf bifurcation. We conjecture that the alignment in phase space between the input noise vector and the center manifold of the Hopf bifurcation is directly linked to these changes. These results are consistent with the possibility of statistical indicators of linear instability being detectable in real EEG time series. However, even in a simple cortical model, we find that these indicators may not necessarily be visible even when bifurcations are present because their expression can depend sensitively on the neuronal pathway of incoming fluctuations.

  10. Auditory midbrain processing is differentially modulated by auditory and visual cortices: An auditory fMRI study.

    Science.gov (United States)

    Gao, Patrick P; Zhang, Jevin W; Fan, Shu-Juan; Sanes, Dan H; Wu, Ed X

    2015-12-01

    The cortex contains extensive descending projections, yet the impact of cortical input on brainstem processing remains poorly understood. In the central auditory system, the auditory cortex contains direct and indirect pathways (via brainstem cholinergic cells) to nuclei of the auditory midbrain, called the inferior colliculus (IC). While these projections modulate auditory processing throughout the IC, single neuron recordings have samples from only a small fraction of cells during stimulation of the corticofugal pathway. Furthermore, assessments of cortical feedback have not been extended to sensory modalities other than audition. To address these issues, we devised blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) paradigms to measure the sound-evoked responses throughout the rat IC and investigated the effects of bilateral ablation of either auditory or visual cortices. Auditory cortex ablation increased the gain of IC responses to noise stimuli (primarily in the central nucleus of the IC) and decreased response selectivity to forward species-specific vocalizations (versus temporally reversed ones, most prominently in the external cortex of the IC). In contrast, visual cortex ablation decreased the gain and induced a much smaller effect on response selectivity. The results suggest that auditory cortical projections normally exert a large-scale and net suppressive influence on specific IC subnuclei, while visual cortical projections provide a facilitatory influence. Meanwhile, auditory cortical projections enhance the midbrain response selectivity to species-specific vocalizations. We also probed the role of the indirect cholinergic projections in the auditory system in the descending modulation process by pharmacologically blocking muscarinic cholinergic receptors. This manipulation did not affect the gain of IC responses but significantly reduced the response selectivity to vocalizations. The results imply that auditory cortical

  11. The timing of cortical granule fusion, content dispersal, and endocytosis during fertilization of the hamster egg: an electrophysiological and histochemical study.

    Science.gov (United States)

    Kline, D; Stewart-Savage, J

    1994-03-01

    To determine the temporal relationship between cortical granule exocytosis and the repetitive calcium transients, which are characteristic of mammalian fertilization, we monitored membrane addition from exocytosis during fertilization of hamster eggs. Continuous measurement of membrane capacitance by applying a 3.1-nA alternating current at 375 Hz showed addition of cortical granule membrane. Simultaneous measurement of membrane potential revealed each calcium transient by the appearance of transient hyperpolarizing responses due to calcium-activated potassium channels in the egg. The initial membrane capacitance of the eggs averaged 736 +/- 44 pF (mean +/- SD; n = 7) and an increase in capacitance of 61 +/- 19 pF occurred within 4 sec of the start of the first hyperpolarizing response (HR) after fertilization. Immediately after the first increase in capacitance there was a gradual decline in membrane capacitance in all eggs and in five/seven eggs the capacitance returned to the unfertilized level in 7.8 +/- 4.4 min. The gradual decline in capacitance after the first increase indicated endocytosis, which was confirmed by the internalization of fluorescently labeled dextran. Superimposed on the gradual decline in membrane capacitance were smaller increases in capacitance that occurred with the second and later HRs. The total increase in capacitance from the first three events averaged 72 +/- 19 pF, representing an average increase in capacitance of about 10% of the capacitance of the unfertilized egg. By labeling eggs before and after permeabilization with two different fluorochromes attached to Lens culinaris agglutinin, we demonstrate that the dispersal of the cortical granules contents does not occur immediately after exocytosis. Our results demonstrate that cortical granule exocytosis in hamster eggs is closely coupled to the periodic increases in calcium, that the contents of the cortical granules are slow to disperse, and that after exocytosis, the surface

  12. Potential protection of green tea polyphenols against 1800 MHz electromagnetic radiation-induced injury on rat cortical neurons.

    Science.gov (United States)

    Liu, Mei-Li; Wen, Jian-Qiang; Fan, Yu-Bo

    2011-10-01

    Radiofrequency electromagnetic fields (EMF) are harmful to public health, but the certain anti-irradiation mechanism is not clear yet. The present study was performed to investigate the possible protective effects of green tea polyphenols against electromagnetic radiation-induced injury in the cultured rat cortical neurons. In this study, green tea polyphenols were used in the cultured cortical neurons exposed to 1800 MHz EMFs by the mobile phone. We found that the mobile phone irradiation for 24 h induced marked neuronal cell death in the MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide) and TUNEL (TdT mediated biotin-dUTP nicked-end labeling) assay, and protective effects of green tea polyphenols on the injured cortical neurons were demonstrated by testing the content of Bcl-2 Assaciated X protein (Bax) in the immunoprecipitation assay and Western blot assay. In our study results, the mobile phone irradiation-induced increases in the content of active Bax were inhibited significantly by green tea polyphenols, while the contents of total Bax had no marked changes after the treatment of green tea polyphenols. Our results suggested a neuroprotective effect of green tea polyphenols against the mobile phone irradiation-induced injury on the cultured rat cortical neurons.

  13. Malformations of Cortical Development

    NARCIS (Netherlands)

    Aronica, Eleonora; Becker, Albert J.; Spreafico, Roberto

    2012-01-01

    Structural abnormalities of the brain are increasingly recognized in patients that suffer from pharmacoresistant focal epilepsies by applying high-resolution imaging techniques. In many of these patients, epilepsy surgery results in control of seizures. Neuropathologically, a broad spectrum of

  14. Mean field methods for cortical network dynamics

    DEFF Research Database (Denmark)

    Hertz, J.; Lerchner, Alexander; Ahmadi, M.

    2004-01-01

    We review the use of mean field theory for describing the dynamics of dense, randomly connected cortical circuits. For a simple network of excitatory and inhibitory leaky integrate- and-fire neurons, we can show how the firing irregularity, as measured by the Fano factor, increases...... with the strength of the synapses in the network and with the value to which the membrane potential is reset after a spike. Generalizing the model to include conductance-based synapses gives insight into the connection between the firing statistics and the high- conductance state observed experimentally in visual...

  15. Direct cortical hemodynamic mapping of somatotopy of pig nostril sensation by functional near-infrared cortical imaging (fNCI).

    Science.gov (United States)

    Uga, Minako; Saito, Toshiyuki; Sano, Toshifumi; Yokota, Hidenori; Oguro, Keiji; Rizki, Edmi Edison; Mizutani, Tsutomu; Katura, Takusige; Dan, Ippeita; Watanabe, Eiju

    2014-05-01

    Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals. Although direct cortical monitoring with fNIRS has been pursued, a high-resolution visualization of hemodynamic changes associated with sensory, motor and cognitive neural responses directly from the cortical surface has yet to be realized. To acquire robust information on the hemodynamics of the cortex, devoid of signal complications in transcranial measurement, we devised a functional near-infrared cortical imaging (fNCI) technique. Here we demonstrate the first direct functional measurement of temporal and spatial patterns of cortical hemodynamics using the fNCI technique. For fNCI, inter-optode distance was set at 5mm, and light leakage from illuminators was prevented by a special optode holder made of a light-shielding rubber sheet. fNCI successfully detected the somatotopy of pig nostril sensation, as assessed in comparison with concurrent and sequential somatosensory-evoked potential (SEP) measurements on the same stimulation sites. Accordingly, the fNCI system realized a direct cortical hemodynamic measurement with a spatial resolution comparable to that of SEP mapping on the rostral region of the pig brain. This study provides an important initial step toward realizing functional cortical hemodynamic monitoring during neurosurgery of human brains. Copyright © 2014. Published by Elsevier Inc.

  16. Osmosis in Cortical Collecting Tubules

    Science.gov (United States)

    Schafer, James A.; Troutman, Susan L.; Andreoli, Thomas E.

    1974-01-01

    The present experiments were designed to evaluate the effects of varying the osmolality of luminal solutions on the antidiuretic hormone (ADH)-independent water and solute permeability properties of isolated rabbit cortical collecting tubules. In the absence of ADH, the osmotic water permeability coefficient (cm s–1) Pfl→b, computed from volume flows from hypotonic lumen to isotonic bath, was 20 ± 4 x 10–4 (SEM); the value of Pfb→l in the absence of ADH, computed from volume flows from isotonic bath to hypertonic lumen, was 88 ± 15 x 10–4 cm s–1. We also measured apparent urea permeability coefficients (cm s–1) from 14C-urea fluxes from lumen to bath (P DDurea l→b) and from bath to lumen (P DDurea b→l). For hypotonic luminal solutions and isotonic bathing solutions, P DDurea l→b was 0.045 ± 0.004 x 10–4 and was unaffected by ADH. The ADH-independent values of P DDurea l→b and P urea b→l were, respectively, 0.216 ± 0.022 x 10–4 cm s–1 and 0.033 ± 0.002 x 10–4 cm s–1 for isotonic bathing solutions and luminal solutions made hypertonic with urea, i.e., there was an absolute increase in urea permeability and asymmetry of urea fluxes. Significantly, P DDurea l→b did not rise when luminal hypertonicity was produced by sucrose; and, bathing fluid hypertonicity did not alter tubular permeability to water or to urea. We interpret these data to indicate that luminal hypertonicity increased the leakiness of tight junctions to water and urea but not sucrose. Since the value of Pfb→l in the absence of ADH, when tight junctions were open to urea, was approximately half of the value of Pfl→b in the presence of ADH, when tight junctions were closed to urea, we conclude that tight junctions are negligible paracellular shunts for lumen to bath osmosis with ADH. These findings, together with those in the preceding paper, are discussed in terms of a solubility-diffusion model for water permeation in which ADH increases water solubility in

  17. SynGAP regulates protein synthesis and homeostatic synaptic plasticity in developing cortical networks.

    Directory of Open Access Journals (Sweden)

    Chih-Chieh Wang

    Full Text Available Disrupting the balance between excitatory and inhibitory neurotransmission in the developing brain has been causally linked with intellectual disability (ID and autism spectrum disorders (ASD. Excitatory synapse strength is regulated in the central nervous system by controlling the number of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs. De novo genetic mutations of the synaptic GTPase-activating protein (SynGAP are associated with ID and ASD. SynGAP is enriched at excitatory synapses and genetic suppression of SynGAP increases excitatory synaptic strength. However, exactly how SynGAP acts to maintain synaptic AMPAR content is unclear. We show here that SynGAP limits excitatory synaptic strength, in part, by suppressing protein synthesis in cortical neurons. The data presented here from in vitro, rat and mouse cortical networks, demonstrate that regulation of translation by SynGAP involves ERK, mTOR, and the small GTP-binding protein Rheb. Furthermore, these data show that GluN2B-containing NMDARs and the cognitive kinase CaMKII act upstream of SynGAP and that this signaling cascade is required for proper translation-dependent homeostatic synaptic plasticity of excitatory synapses in developing cortical networks.

  18. Atlas-free surface reconstruction of the cortical grey-white interface in infants.

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    François Leroy

    Full Text Available BACKGROUND: The segmentation of the cortical interface between grey and white matter in magnetic resonance images (MRI is highly challenging during the first post-natal year. First, the heterogeneous brain maturation creates important intensity fluctuations across regions. Second, the cortical ribbon is highly folded creating complex shapes. Finally, the low tissue contrast and partial volume effects hamper cortex edge detection in parts of the brain. METHODS AND FINDINGS: We present an atlas-free method for segmenting the grey-white matter interface of infant brains in T2-weighted (T2w images. We used a broad characterization of tissue using features based not only on local contrast but also on geometric properties. Furthermore, inaccuracies in localization were reduced by the convergence of two evolving surfaces located on each side of the inner cortical surface. Our method has been applied to eleven brains of one- to four-month-old infants. Both quantitative validations against manual segmentations and sulcal landmarks demonstrated good performance for infants younger than two months old. Inaccuracies in surface reconstruction increased with age in specific brain regions where the tissue contrast decreased with maturation, such as in the central region. CONCLUSIONS: We presented a new segmentation method which achieved good to very good performance at the grey-white matter interface depending on the infant age. This method should reduce manual intervention and could be applied to pathological brains since it does not require any brain atlas.

  19. Altered cortical anatomical networks in temporal lobe epilepsy

    Science.gov (United States)

    Lv, Bin; He, Huiguang; Lu, Jingjing; Li, Wenjing; Dai, Dai; Li, Meng; Jin, Zhengyu

    2011-03-01

    Temporal lobe epilepsy (TLE) is one of the most common epilepsy syndromes with focal seizures generated in the left or right temporal lobes. With the magnetic resonance imaging (MRI), many evidences have demonstrated that the abnormalities in hippocampal volume and the distributed atrophies in cortical cortex. However, few studies have investigated if TLE patients have the alternation in the structural networks. In the present study, we used the cortical thickness to establish the morphological connectivity networks, and investigated the network properties using the graph theoretical methods. We found that all the morphological networks exhibited the small-world efficiency in left TLE, right TLE and normal groups. And the betweenness centrality analysis revealed that there were statistical inter-group differences in the right uncus region. Since the right uncus located at the right temporal lobe, these preliminary evidences may suggest that there are topological alternations of the cortical anatomical networks in TLE, especially for the right TLE.

  20. Cortical laminar necrosis in brain infarcts: serial MRI

    Energy Technology Data Exchange (ETDEWEB)

    Siskas, N.; Lefkopoulos, A.; Ioannidis, I.; Charitandi, A.; Dimitriadis, A.S. [Radiology Department, AHEPA University Hospital, Aristotele University of Thessaloniki (Greece)

    2003-05-01

    High-signal cortical lesions are observed on T1-weighted images in cases of brain infarct. Histological examination has demonstrated these to be ''cortical laminar necrosis'', without haemorrhage or calcification. We report serial MRI in this condition in 12 patients with brain infarcts. We looked at high-signal lesions on T1-weighted images, chronological changes in signal intensity and contrast enhancement. High-signal cortical lesions began to appear about 2 weeks after the ictus, were prominent at 1 - 2 months, then became less evident, but occasionally remained for up to 1.5 years. They gave high signal or were isointense on T2-weighted images and did not give low signal at any stage. Contrast enhancement of these lesions was prominent at 1 - 2 months, and less apparent from 3 months, but was seen up to 5 months. (orig.)

  1. Glycine Receptor α2 Subunit Activation Promotes Cortical Interneuron Migration

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    Ariel Avila

    2013-08-01

    Full Text Available Glycine receptors (GlyRs are detected in the developing CNS before synaptogenesis, but their function remains elusive. This study demonstrates that functional GlyRs are expressed by embryonic cortical interneurons in vivo. Furthermore, genetic disruption of these receptors leads to interneuron migration defects. We discovered that extrasynaptic activation of GlyRs containing the α2 subunit in cortical interneurons by endogenous glycine activates voltage-gated calcium channels and promotes calcium influx, which further modulates actomyosin contractility to fine-tune nuclear translocation during migration. Taken together, our data highlight the molecular events triggered by GlyR α2 activation that control cortical tangential migration during embryogenesis.

  2. Congenital malformations of the supratentorial brain. Pt. 1. Disorders of cortical development

    International Nuclear Information System (INIS)

    Ertl-Wagner, B.; Rummeny, C.; Reiser, M.F.

    2003-01-01

    Disorders of supratentorial cortical development are usually divided into disorders of neuronal proliferation, neuronal migration and cortical organization. Based upon molecular biologic discoveries, a modified classification has recently been proposed. The category of malformations of abnormal neuronal and glial proliferation and apoptosis now includes microlissencephalies, megalencephalies, hemimegalencephalies and cortical dysplasias with balloon cells. Malformations due to abnormal neuronal migration now subsume the lissencephaly spectrum including the subcortical band heterotopias, the cobblestone complex and the group of heterotopias. Malformations due to abnormal cortical organization include the spectrum of polymicrogyria and schizencephaly as well as cortical dysplasias without balloon cells. High-resolution magnetic resonance imaging (MRI) has led to an increasing awareness of these malformations. This article aims to illustrate the classification, MRI presentation and relevant clinical features of the most commonly encountered disorders of cortical development. (orig.) [de

  3. Brain cortical thickness in male adolescents with serious substance use and conduct problems.

    Science.gov (United States)

    Chumachenko, Serhiy Y; Sakai, Joseph T; Dalwani, Manish S; Mikulich-Gilbertson, Susan K; Dunn, Robin; Tanabe, Jody; Young, Susan; McWilliams, Shannon K; Banich, Marie T; Crowley, Thomas J

    2015-01-01

    Adolescents with substance use disorder (SUD) and conduct problems exhibit high levels of impulsivity and poor self-control. Limited work to date tests for brain cortical thickness differences in these youths. To investigate differences in cortical thickness between adolescents with substance use and conduct problems and controls. We recruited 25 male adolescents with SUD, and 19 male adolescent controls, and completed structural 3T magnetic resonance brain imaging. Using the surface-based morphometry software FreeSurfer, we completed region-of-interest (ROI) analyses for group cortical thickness differences in left, and separately right, inferior frontal gyrus (IFG), orbitofrontal cortex (OFC) and insula. Using FreeSurfer, we completed whole-cerebrum analyses of group differences in cortical thickness. Versus controls, the SUD group showed no cortical thickness differences in ROI analyses. Controlling for age and IQ, no regions with cortical thickness differences were found using whole-cerebrum analyses (though secondary analyses co-varying IQ and whole-cerebrum cortical thickness yielded a between-group cortical thickness difference in the left posterior cingulate/precuneus). Secondary findings showed that the SUD group, relative to controls, demonstrated significantly less right > left asymmetry in IFG, had weaker insular-to-whole-cerebrum cortical thickness correlations, and showed a positive association between conduct disorder symptom count and cortical thickness in a superior temporal gyrus cluster. Functional group differences may reflect a more nuanced cortical morphometric difference than ROI cortical thickness. Further investigation of morphometric differences is needed. If replicable findings can be established, they may aid in developing improved diagnostic or more targeted treatment approaches.

  4. Do studies on cortical plasticity provide a rationale for using non invasive brain stimulation as a treatment for Parkinson’s disease patients?

    Directory of Open Access Journals (Sweden)

    Giacomo eKoch

    2013-11-01

    Full Text Available Animal models of Parkinson’s disease (PD have shown that key mechanisms of cortical plasticity such as long-term potentiation (LTP and long-term depression (LTD can be impaired by the PD pathology. In humans protocols of non-invasive brain stimulation, such as paired associative stimulation (PAS and theta burst stimulation (TBS, can be used to investigate cortical plasticity of the primary motor cortex. Through the amplitude of the motor evoked potential (MEP these transcranial magnetic stimulation methods allow to measure both LTP-like and LTD-like mechanisms of cortical plasticity. So far these protocols have reported some controversial findings when tested in PD patients. While various studies described evidence for reduced LTP- and LTD-like plasticity, others showed different results, demonstrating increased LTP-like and normal LTD-like plasticity. Recent evidence provided support to the hypothesis that these different patterns of cortical plasticity likely depend on the stage of the disease and on the concomitant administration of levo-dopa. However, it still unclear how and if these altered mechanisms of cortical plasticity can be taken as a reliable model to build appropriate protocols aimed at treating PD symptoms b

  5. Anterior Cortical Development During Adolescence in Bipolar Disorder.

    Science.gov (United States)

    Najt, Pablo; Wang, Fei; Spencer, Linda; Johnston, Jennifer A Y; Cox Lippard, Elizabeth T; Pittman, Brian P; Lacadie, Cheryl; Staib, Lawrence H; Papademetris, Xenophon; Blumberg, Hilary P

    2016-02-15

    Increasing evidence supports a neurodevelopmental model for bipolar disorder (BD), with adolescence as a critical period in its development. Developmental abnormalities of anterior paralimbic and heteromodal frontal cortices, key structures in emotional regulation processes and central in BD, are implicated. However, few longitudinal studies have been conducted, limiting understanding of trajectory alterations in BD. In this study, we performed longitudinal neuroimaging of adolescents with and without BD and assessed volume changes over time, including changes in tissue overall and within gray and white matter. Larger decreases over time in anterior cortical volumes in the adolescents with BD were hypothesized. Gray matter decreases and white matter increases are typically observed during adolescence in anterior cortices. It was hypothesized that volume decreases over time in BD would reflect alterations in those processes, showing larger gray matter contraction and decreased white matter expansion. Two high-resolution magnetic resonance imaging scans were obtained approximately 2 years apart for 35 adolescents with bipolar I disorder (BDI) and 37 healthy adolescents. Differences over time between groups were investigated for volume overall and specifically for gray and white matter. Relative to healthy adolescents, adolescents with BDI showed greater volume contraction over time in a region including insula and orbitofrontal, rostral, and dorsolateral prefrontal cortices (p adolescence in BDI in anterior cortices, including altered developmental trajectories of anterior gray and white matter. Published by Elsevier Inc.

  6. Cortical Thickness Changes Associated with Photoparoxysmal Response

    DEFF Research Database (Denmark)

    Hanganu, Alexandru; Groppa, Stanislav A; Deuschl, Günther

    2014-01-01

    Photoparoxysmal response (PPR) is an EEG trait of spike and spike-wave discharges in response to photic stimulation that is closely linked to idiopathic generalized epilepsy (IGE). In our previous studies we showed that PPR is associated with functional alterations in the occipital and frontal co...... in the occipital lobe, frontoparietal regions and temporal lobe, which also show functional changes associated with PPR. Patients with epilepsy present changes in the temporal lobe and supplementary motor area.......-positive-subjects presented a significant decrease of cortical thickness in the temporal cortex in the same group contrast. IGE patients exhibited lower cortical thickness in the temporal lobe bilaterally and in the right paracentral region in comparison to PPR-positive-subjects. Our study demonstrates structural changes......Photoparoxysmal response (PPR) is an EEG trait of spike and spike-wave discharges in response to photic stimulation that is closely linked to idiopathic generalized epilepsy (IGE). In our previous studies we showed that PPR is associated with functional alterations in the occipital and frontal...

  7. Cortical-Cortical Interactions And Sensory Information Processing in Autism

    Science.gov (United States)

    2008-04-30

    significant development for disseminating the results of biomedical research in our lifetime." Sir Paul Nurse , Cancer Research UK Your research papers...of the evidence for local cortical over-connectivity is anecdotal. Belmonte and colleagues suggested the co-morbidity with epilepsy that is highly...Tomma-Halme J, Lahti-Nuuttila P, Service E, Virsu V: Rate of information segregation in developmentally dyslexic children . Brain Lang 2000, 75:66-81

  8. Cortical Motor Circuits after Piano Training in Adulthood: Neurophysiologic Evidence.

    Directory of Open Access Journals (Sweden)

    Elise Houdayer

    Full Text Available The neuronal mechanisms involved in brain plasticity after skilled motor learning are not completely understood. We aimed to study the short-term effects of keyboard training in music-naive subjects on the motor/premotor cortex activity and interhemispheric interactions, using electroencephalography and transcranial magnetic stimulation (TMS. Twelve subjects (experimental group underwent, before and after a two week-piano training: (1 hand-motor function tests: Jamar, grip and nine-hole peg tests; (2 electroencephalography, evaluating the mu rhythm task-related desynchronization (TRD during keyboard performance; and (3 TMS, targeting bilateral abductor pollicis brevis (APB and abductor digiti minimi (ADM, to obtain duration and area of ipsilateral silent period (ISP during simultaneous tonic contraction of APB and ADM. Data were compared with 13 controls who underwent twice these measurements, in a two-week interval, without undergoing piano training. Every subject in the experimental group improved keyboard performance and left-hand nine-hole peg test scores. Pre-training, ISP durations were asymmetrical, left being longer than right. Post-training, right ISPAPB increased, leading to symmetrical ISPAPB. Mu TRD during motor performance became more focal and had a lesser amplitude than in pre-training, due to decreased activity over ventral premotor cortices. No such changes were evidenced in controls. We demonstrated that a 10-day piano-training was associated with balanced interhemispheric interactions both at rest and during motor activation. Piano training, in a short timeframe, may reshape local and inter-hemispheric motor cortical circuits.

  9. Effects of deuterium oxide and galvanic vestibular stimulation on visual cortical cell function

    International Nuclear Information System (INIS)

    Reinis, S.; Landolt, J.P.; Weiss, D.S.; Money, K.E.

    1984-01-01

    The spontaneous and evoked unit activities of complex visual cortical cells were recorded from Brodmann's area 18 in immobilized, unanesthetized cats before, during, and after stimulation of the vestibular system. The vestibular system was stimulated by intravenous injection of deuterium oxide (D2O)--a noted nystagmogenic agent--or by direct galvanic stimulation of the labyrinth. Measures of the receptive-field areas, poststimulus time histograms, directional preferences, and the optimal speed of the light bar stimulating the cell were obtained before and after the application of D2O. Directional preferences were determined in a novel manner, using a method derived from a hierarchical clustering technique. Data were collected and analyzed from a) visual cortical cells in cats with intact labyrinths, b) visual cortical cells in cats following bilateral labrinthectomies, and c) nonvisual cortical cells in cats with intact labyrinths. The other cellular characteristics were also altered by the D2O. Galvanic stimulation of the labyrinth resembles, in its effects, the injection of D2O. In labyrinth-intact cats, the time course of area 18 spontaneous activity dramatically increased 30 min or more after D2O was administered. It peaked 2-3 h later and still had not returned to preinjection levels even 7 h after the D2O administration. In bilaterally labyrinthectomized cats, the spontaneous activity of the visual cells did not change following D2O administration. In nonvisual cells from labyrinth-intact cats, the spontaneous activity demonstrated a slight but significant decrease over time after D2O injection. In pilot studies, the cats were injected with D2O. Within 8-10 min afterward, signs of positional nystagmus commenced; and within 30 min, problems in maintaining balance were noted. This continued for 7-8 h before disappearing. In the labyrinthectomized animals, such effects were not observed

  10. Effects of deuterium oxide and galvanic vestibular stimulation on visual cortical cell function

    Energy Technology Data Exchange (ETDEWEB)

    Reinis, S.; Landolt, J.P.; Weiss, D.S.; Money, K.E.

    1984-03-01

    The spontaneous and evoked unit activities of complex visual cortical cells were recorded from Brodmann's area 18 in immobilized, unanesthetized cats before, during, and after stimulation of the vestibular system. The vestibular system was stimulated by intravenous injection of deuterium oxide (D2O)--a noted nystagmogenic agent--or by direct galvanic stimulation of the labyrinth. Measures of the receptive-field areas, poststimulus time histograms, directional preferences, and the optimal speed of the light bar stimulating the cell were obtained before and after the application of D2O. Directional preferences were determined in a novel manner, using a method derived from a hierarchical clustering technique. Data were collected and analyzed from a) visual cortical cells in cats with intact labyrinths, b) visual cortical cells in cats following bilateral labrinthectomies, and c) nonvisual cortical cells in cats with intact labyrinths. The other cellular characteristics were also altered by the D2O. Galvanic stimulation of the labyrinth resembles, in its effects, the injection of D2O. In labyrinth-intact cats, the time course of area 18 spontaneous activity dramatically increased 30 min or more after D2O was administered. It peaked 2-3 h later and still had not returned to preinjection levels even 7 h after the D2O administration. In bilaterally labyrinthectomized cats, the spontaneous activity of the visual cells did not change following D2O administration. In nonvisual cells from labyrinth-intact cats, the spontaneous activity demonstrated a slight but significant decrease over time after D2O injection. In pilot studies, the cats were injected with D2O. Within 8-10 min afterward, signs of positional nystagmus commenced; and within 30 min, problems in maintaining balance were noted. This continued for 7-8 h before disappearing. In the labyrinthectomized animals, such effects were not observed.

  11. Depth-dependent flow and pressure characteristics in cortical microvascular networks.

    Directory of Open Access Journals (Sweden)

    Franca Schmid

    2017-02-01

    Full Text Available A better knowledge of the flow and pressure distribution in realistic microvascular networks is needed for improving our understanding of neurovascular coupling mechanisms and the related measurement techniques. Here, numerical simulations with discrete tracking of red blood cells (RBCs are performed in three realistic microvascular networks from the mouse cerebral cortex. Our analysis is based on trajectories of individual RBCs and focuses on layer-specific flow phenomena until a cortical depth of 1 mm. The individual RBC trajectories reveal that in the capillary bed RBCs preferentially move in plane. Hence, the capillary flow field shows laminar patterns and a layer-specific analysis is valid. We demonstrate that for RBCs entering the capillary bed close to the cortical surface (< 400 μm the largest pressure drop takes place in the capillaries (37%, while for deeper regions arterioles are responsible for 61% of the total pressure drop. Further flow characteristics, such as capillary transit time or RBC velocity, also vary significantly over cortical depth. Comparison of purely topological characteristics with flow-based ones shows that a combined interpretation of topology and flow is indispensable. Our results provide evidence that it is crucial to consider layer-specific differences for all investigations related to the flow and pressure distribution in the cortical vasculature. These findings support the hypothesis that for an efficient oxygen up-regulation at least two regulation mechanisms must be playing hand in hand, namely cerebral blood flow increase and microvascular flow homogenization. However, the contribution of both regulation mechanisms to oxygen up-regulation likely varies over depth.

  12. Vestibulo-cortical Hemispheric Dominance: the link between Anxiety and the Vestibular System?

    Science.gov (United States)

    Bednarczuk, Nadja F; Casanovas Ortega, Marta; Fluri, Anne-Sophie; Arshad, Qadeer

    2018-05-16

    Vestibular processing and anxiety networks are functionally intertwined, as demonstrated by reports of reciprocal influences upon each other. Yet whether there is an underlying link between these two systems remains unknown Previous findings have highlighted the involvement of hemispheric lateralisation in processing of both anxiety and vestibular signals. Accordingly, we explored the interaction between vestibular cortical processing and anxiety by assessing the relationship between anxiety levels and the degree of hemispheric lateralisation of vestibulo-cortical processing in 64 right-handed, healthy individuals. Vestibulo-cortical hemispheric lateralisation was determined by gaging the degree of caloric-induced nystagmus suppression following modulation of cortical excitability using trans-cranial direct current stimulation targeted over the posterior parietal cortex, an area implicated in the processing of vestibular signals. The degree of nystagmus suppression yields an objective biomarker, allowing the quantification of the degree of right vestibulo-cortical hemisphere dominance. Anxiety levels were quantified using the Trait component of the Spielberger State-Trait Anxiety Questionnaire. Our findings demonstrate that the degree of an individual's vestibulo-cortical hemispheric dominance correlates with their anxiety levels. That is, those individuals with greater right hemispheric vestibulo-cortical dominance exhibited lower levels of anxiety. By extension, our results support the notion that hemispheric lateralisation determines an individual's emotional processing, thereby linking cortical circuits involved in processing anxiety and vestibular signals respectively. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. Control of Somatosensory Cortical Processing by Thalamic Posterior Medial Nucleus: A New Role of Thalamus in Cortical Function.

    Directory of Open Access Journals (Sweden)

    Carlos Castejon

    Full Text Available Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1 in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane-anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas.

  14. Ultrasound evaluation of cortical brain development in fetuses with intrauterine growth restriction.

    Science.gov (United States)

    Businelli, Caterina; de Wit, Charlotte; Visser, Gerard H A; Pistorius, Lourens R

    2014-09-10

    Abstract Objective: We evaluated the ultrasound appearance of brain volume and cortical development in fetuses with early growth restriction and placental insufficiency. Methods: We examined a cohort of 20 fetuses with severe intrauterine growth restriction (IUGR) and evidence of placental insufficiency by three-dimensional (3D) ultrasound between 24 and 34 weeks. We graded cortical development and measured the supratentorial intracranial volume. The cortical grading and volume were compared to data obtained from a reference population of 28 adequate for gestational age (AGA) fetuses. Results: Ultrasound examinations were performed in 20 fetuses with IUGR. The biometry and brain volume were significantly reduced in IUGR fetuses. There was evidence of accelerated cortical development in IUGR fetuses. Conclusion: This study confirms that the smaller brain volume in IUGR fetuses, with normal or accelerated cortical maturation as previously depicted with postnatal MRI examination, can be demonstrated by prenatal 3D ultrasound.

  15. Cortical activation in patients with functional hemispherectomy.

    Science.gov (United States)

    Leonhardt, G; Bingel, U; Spiekermann, G; Kurthen, M; Müller, S; Hufnagel, A

    2001-10-01

    Functional hemispherectomy, a safe and effective therapeutical procedure in medically intractable epilepsy, offers the chance to investigate a strictly unilateral cortical activation in ipsilateral limb movement. We assessed the pattern of cortical activation in a group of patients following functional hemispherectomy. We measured regional cerebral blood flow (rCBF) in 6 patients postoperatively and 6 normal subjects with positron emission tomography using 15[O]H2O as a tracer. Brain activation was achieved by passive elbow movements of the affected arm. Analysis of group results and between-group comparisons were performed with statistical parametric mapping, (SPM96). In normal subjects brain activation was found contralaterally in the cranial sensorimotor cortex and the supplementary motor area and ipsilaterally in the inferior parietal cortex. In patients significant rCBF increases were found in the inferior parietal cortex, caudal sensorimotor cortex and the supplementary motor area ipsilaterally. The activation was weaker than in normal subjects. Compared with normal subjects patients showed additional activation in the premotor cortex, caudal sensorimotor cortex and the inferior parietal cortex of the remaining hemisphere. Less activation compared with normal subjects was found in the cranial sensorimotor cortex and the supplementary motor area. A functional network connecting the inferior parietal cortex, premotor cortex and the supplementary motor area as well as the existence of ipsilateral projections originating from these regions may explain why these areas are predominantly involved in reorganization confined to a single hemisphere.

  16. Influence of spontaneous rhythm on movement-related cortical potential

    DEFF Research Database (Denmark)

    Yao, Lin; Chen, Mei Lin; Sheng, Xinjun

    2017-01-01

    We have recently developed an associative Brain-Computer Interface (BCI) for neuromodulation in chronic and acute stroke patients that leads to functional improvements. The control signal is the movement related cortical potential (MRCP) that develops prior to movement execution. The MRCP increases...

  17. Zic deficiency in the cortical marginal zone and meninges results in cortical lamination defects resembling those in type II lissencephaly.

    Science.gov (United States)

    Inoue, Takashi; Ogawa, Masaharu; Mikoshiba, Katsuhiko; Aruga, Jun

    2008-04-30

    The formation of the highly organized cortical structure depends on the production and correct placement of the appropriate number and types of neurons. The Zic family of zinc-finger transcription factors plays essential roles in regulating the proliferation and differentiation of neuronal progenitors in the medial forebrain and the cerebellum. Examination of the expression of Zic genes demonstrated that Zic1, Zic2, and Zic3 were expressed by the progenitor cells in the septum and cortical hem, the sites of generation of the Cajal-Retzius (CR) cells. Immunohistochemical studies have revealed that Zic proteins were abundantly expressed in the meningeal cells and that the majority of the CR cells distributed in the medial and dorsal cortex also expressed Zic proteins in the mid-late embryonic and postnatal cortical marginal zones. During embryonic cortical development, Zic1/Zic3 double-mutant and hypomorphic Zic2 mutant mice showed a reduction in the number of CR cells in the rostral cortex, whereas the cell number remained unaffected in the caudal cortex. These mutants also showed mislocalization of the CR cells and cortical lamination defects, resembling the changes noted in type II (cobblestone) lissencephaly, throughout the brain. In the Zic1/3 mutant, reduced proliferation of the meningeal cells was observed before the thinner and disrupted organization of the pial basement membrane (BM) with reduced expression of the BM components and the meningeal cell-derived secretory factor. These defects correlated with the changes in the end feet morphology of the radial glial cells. These findings indicate that the Zic genes play critical roles in cortical development through regulating the proliferation of meningeal cells and the pial BM assembly.

  18. Wireless Cortical Brain-Machine Interface for Whole-Body Navigation in Primates

    Science.gov (United States)

    Rajangam, Sankaranarayani; Tseng, Po-He; Yin, Allen; Lehew, Gary; Schwarz, David; Lebedev, Mikhail A.; Nicolelis, Miguel A. L.

    2016-03-01

    Several groups have developed brain-machine-interfaces (BMIs) that allow primates to use cortical activity to control artificial limbs. Yet, it remains unknown whether cortical ensembles could represent the kinematics of whole-body navigation and be used to operate a BMI that moves a wheelchair continuously in space. Here we show that rhesus monkeys can learn to navigate a robotic wheelchair, using their cortical activity as the main control signal. Two monkeys were chronically implanted with multichannel microelectrode arrays that allowed wireless recordings from ensembles of premotor and sensorimotor cortical neurons. Initially, while monkeys remained seated in the robotic wheelchair, passive navigation was employed to train a linear decoder to extract 2D wheelchair kinematics from cortical activity. Next, monkeys employed the wireless BMI to translate their cortical activity into the robotic wheelchair’s translational and rotational velocities. Over time, monkeys improved their ability to navigate the wheelchair toward the location of a grape reward. The navigation was enacted by populations of cortical neurons tuned to whole-body displacement. During practice with the apparatus, we also noticed the presence of a cortical representation of the distance to reward location. These results demonstrate that intracranial BMIs could restore whole-body mobility to severely paralyzed patients in the future.

  19. Cortical phase changes in Alzheimer's disease at 7T MRI: a novel imaging marker.

    Science.gov (United States)

    van Rooden, Sanneke; Versluis, Maarten J; Liem, Michael K; Milles, Julien; Maier, Andrea B; Oleksik, Ania M; Webb, Andrew G; van Buchem, Mark A; van der Grond, Jeroen

    2014-01-01

    Postmortem studies have indicated the potential of high-field magnetic resonance imaging (MRI) to visualize amyloid depositions in the cerebral cortex. The aim of this study is to test this hypothesis in patients with Alzheimer's disease (AD). T2*-weighted MRI was performed in 16 AD patients and 15 control subjects. All magnetic resonance images were scored qualitatively by visual assessment, and quantitatively by measuring phase shifts in the cortical gray matter and hippocampus. Statistical analysis was performed to assess differences between groups. Patients with AD demonstrated an increased phase shift in the cortex in the temporoparietal, frontal, and parietal regions (P < .005), and this was associated with individual Mini-Mental State Examination scores (r = -0.54, P < .05). Increased cortical phase shift in AD patients demonstrated on 7-tesla T2*-weighted MRI is a potential new biomarker for AD, which may reflect amyloid pathology in the early stages. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  20. Altered modular organization of structural cortical networks in children with autism.

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    Feng Shi

    Full Text Available Autism is a complex developmental disability that characterized by deficits in social interaction, language skills, repetitive stereotyped behaviors and restricted interests. Although great heterogeneity exists, previous findings suggest that autism has atypical brain connectivity patterns and disrupted small-world network properties. However, the organizational alterations in the autistic brain network are still poorly understood. We explored possible organizational alterations of 49 autistic children and 51 typically developing controls, by investigating their brain network metrics that are constructed upon cortical thickness correlations. Three modules were identified in controls, including cortical regions associated with brain functions of executive strategic, spatial/auditory/visual, and self-reference/episodic memory. There are also three modules found in autistic children with similar patterns. Compared with controls, autism demonstrates significantly reduced gross network modularity, and a larger number of inter-module connections. However, the autistic brain network demonstrates increased intra- and inter-module connectivity in brain regions including middle frontal gyrus, inferior parietal gyrus, and cingulate, suggesting one underlying compensatory mechanism associated with brain functions of self-reference and episodic memory. Results also show that there is increased correlation strength between regions inside frontal lobe, as well as impaired correlation strength between frontotemporal and frontoparietal regions. This alteration of correlation strength may contribute to the organization alteration of network structures in autistic brains.

  1. Deep brain stimulation of the amygdala alleviates fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory.

    Science.gov (United States)

    Sui, Li; Huang, SiJia; Peng, BinBin; Ren, Jie; Tian, FuYing; Wang, Yan

    2014-07-01

    Deep brain stimulation (DBS) of the amygdala has been demonstrated to modulate hyperactivity of the amygdala, which is responsible for the symptoms of post-traumatic stress disorder (PTSD), and thus might be used for the treatment of PTSD. However, the underlying mechanism of DBS of the amygdala in the modulation of the amygdala is unclear. The present study investigated the effects of DBS of the amygdala on synaptic transmission and synaptic plasticity at cortical inputs to the amygdala, which is critical for the formation and storage of auditory fear memories, and fear memories. The results demonstrated that auditory fear conditioning increased single-pulse-evoked field excitatory postsynaptic potentials in the cortical-amygdala pathway. Furthermore, auditory fear conditioning decreased the induction of paired-pulse facilitation and long-term potentiation, two neurophysiological models for studying short-term and long-term synaptic plasticity, respectively, in the cortical-amygdala pathway. In addition, all these auditory fear conditioning-induced changes could be reversed by DBS of the amygdala. DBS of the amygdala also rescued auditory fear conditioning-induced enhancement of long-term retention of fear memory. These findings suggested that DBS of the amygdala alleviating fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory may underlie the neuromodulatory role of DBS of the amygdala in activities of the amygdala.

  2. Progesterone increases brain-derived neuroptrophic factor expression and protects against glutamate toxicity in a mitogen-activated protein kinase- and phosphoinositide-3 kinase-dependent manner in cerebral cortical explants.

    Science.gov (United States)

    Kaur, Paramjit; Jodhka, Parmeet K; Underwood, Wendy A; Bowles, Courtney A; de Fiebre, Nancyellen C; de Fiebre, Christopher M; Singh, Meharvan

    2007-08-15

    The higher prevalence and risk for Alzheimer's disease in women relative to men has been partially attributed to the precipitous decline in gonadal hormone levels that occurs in women following the menopause. Although considerable attention has been focused on the consequence of estrogen loss, and thus estrogen's neuroprotective potential, it is important to recognize that the menopause results in a precipitous decline in progesterone levels as well. In fact, progesterone is neuroprotective, although the precise mechanisms involved remain unclear. Based on our previous observation that progesterone elicits the phosphorylation of ERK and Akt, key effectors of the neuroprotective mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase (PI3-K) pathways, respectively, we determined whether activation of either of these pathways was necessary for progesterone-induced protection. With organotypic explants (slice culture) of the cerebral cortex, we found that progesterone protected against glutamate-induced toxicity. Furthermore, these protective effects were inhibited by either the MEK1/2 inhibitor UO126 or the PI3-K inhibitor LY294002, supporting the requirement for both the MAPK and PI3-K pathways in progesterone-induced protection. In addition, at a concentration and duration of treatment consistent with our neuroprotection data, progesterone also increased the expression of brain-derived neurotrophic factor (BDNF), at the level of both protein and mRNA. This induction of BDNF may be relevant to the protective effects of progesterone, in that inhibition of Trk signaling, with K252a, inhibited the protective effects of progesterone. Collectively, these data suggest that progesterone is protective via multiple and potentially related mechanisms. (c) 2007 Wiley-Liss, Inc. Copyright 2007 Wiley-Liss, Inc.

  3. Population spikes in cortical networks during different functional states.

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    Shirley eMark

    2012-07-01

    Full Text Available Brain computational challenges vary between behavioral states. Engaged animals react according to incoming sensory information, while in relaxed and sleeping states consolidation of the learned information is believed to take place. Different states are characterized by different forms of cortical activity. We study a possible neuronal mechanism for generating these diverse dynamics and suggest their possible functional significance. Previous studies demonstrated that brief synchronized increase in a neural firing (Population Spikes can be generated in homogenous recurrent neural networks with short-term synaptic depression. Here we consider more realistic networks with clustered architecture. We show that the level of synchronization in neural activity can be controlled smoothly by network parameters. The network shifts from asynchronous activity to a regime in which clusters synchronized separately, then, the synchronization between the clusters increases gradually to fully synchronized state. We examine the effects of different synchrony levels on the transmission of information by the network. We find that the regime of intermediate synchronization is preferential for the flow of information between sparsely connected areas. Based on these results, we suggest that the regime of intermediate synchronization corresponds to engaged behavioral state of the animal, while global synchronization is exhibited during relaxed and sleeping states.

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

    Science.gov (United States)

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

    2015-01-15

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

  5. Acute hepatic encephalopathy with diffuse cortical lesions

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    Arnold, S.M.; Spreer, J.; Schumacher, M. [Section of Neuroradiology, Univ. of Freiburg (Germany); Els, T. [Dept. of Neurology, University of Freiburg (Germany)

    2001-07-01

    Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

  6. Communication and Wiring in the Cortical Connectome

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    Julian eBudd

    2012-10-01

    Full Text Available In cerebral cortex, the huge mass of axonal wiring that carries information between near and distant neurons is thought to provide the neural substrate for cognitive and perceptual function. The goal of mapping the connectivity of cortical axons at different spatial scales, the cortical connectome, is to trace the paths of information flow in cerebral cortex. To appreciate the relationship between the connectome and cortical function, we need to discover the nature and purpose of the wiring principles underlying cortical connectivity. A popular explanation has been that axonal length is strictly minimized both within and between cortical regions. In contrast, we have hypothesized the existence of a multi-scale principle of cortical wiring where to optimise communication there is a trade-off between spatial (construction and temporal (routing costs. Here, using recent evidence concerning cortical spatial networks we critically evaluate this hypothesis at neuron, local circuit, and pathway scales. We report three main conclusions. First, the axonal and dendritic arbor morphology of single neocortical neurons may be governed by a similar wiring principle, one that balances the conservation of cellular material and conduction delay. Second, the same principle may be observed for fibre tracts connecting cortical regions. Third, the absence of sufficient local circuit data currently prohibits any meaningful assessment of the hypothesis at this scale of cortical organization. To avoid neglecting neuron and microcircuit levels of cortical organization, the connectome framework should incorporate more morphological description. In addition, structural analyses of temporal cost for cortical circuits should take account of both axonal conduction and neuronal integration delays, which appear mostly of the same order of magnitude. We conclude the hypothesized trade-off between spatial and temporal costs may potentially offer a powerful explanation for

  7. Acute hepatic encephalopathy with diffuse cortical lesions

    International Nuclear Information System (INIS)

    Arnold, S.M.; Spreer, J.; Schumacher, M.; Els, T.

    2001-01-01

    Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

  8. The Unique Brain Anatomy of Meditation Practitioners: Alterations in Cortical Gyrification

    Directory of Open Access Journals (Sweden)

    Eileen eLuders

    2012-02-01

    Full Text Available Several cortical regions are reported to vary in meditation practitioners. However, since prior analyses were focused on examining gray matter or cortical thickness, additional effects with respect to other cortical features might have remained undetected. Gyrification (the pattern and degree of cortical folding is an important cerebral characteristic related to the geometry of the brain’s surface. Cortical folding occurs early in development and might be linked to behavioral traits. Thus, exploring cortical gyrification in long-term meditators may provide additional clues with respect to the underlying anatomical correlates of meditation. This study examined cortical gyrification in a large sample (n=100 of meditators and controls, carefully matched for sex and age. Cortical gyrification was established via calculating mean curvature across thousands of vertices on individual cortical surface models. Pronounced group differences indicating larger gyrification in meditators were evident within the left precentral gyrus, right fusiform gyrus, right cuneus, as well as left and right anterior dorsal insula (the latter representing the global significance maximum. Although the exact functional implications of larger cortical gyrification remain to be established, these findings suggest the insula to be a key structure involved in aspects of meditation. For example, variations in insular complexity could affect the regulation of well-known distractions in the process of meditation, such as daydreaming, mind-wandering, and projections into past or future. Moreover, given that meditators are masters in introspection, awareness, and emotional control, increased insular gyrification may reflect an ideal integration of autonomic, affective, and cognitive processes. Due to the cross-sectional nature of this study, further research is necessary determine the relative contribution of nature and nurture to links between cortical gyrification and meditation.

  9. Human cerebral cortices: signal variation on diffusion-weighted MR imaging

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    Asao, Chiaki [Kumamoto Regional Medical Center, Department of Radiology, Kumamoto (Japan); National Hospital Organization Kumamoto Medical Center, Department of Radiology, Kumamoto (Japan); Hirai, Toshinori; Yamashita, Yasuyuki [Kumamoto University Graduate School of Medical Sciences, Department of Diagnostic Radiology, Kumamoto (Japan); Yoshimatsu, Shunji [National Hospital Organization Kumamoto Medical Center, Department of Radiology, Kumamoto (Japan); Matsukawa, Tetsuya; Imuta, Masanori [Kumamoto Regional Medical Center, Department of Radiology, Kumamoto (Japan); Sagara, Katsuro [Kumamoto Regional Medical Center, Department of Internal Medicine, Kumamoto (Japan)

    2008-03-15

    We have often encountered high signal intensity (SI) of the cingulate gyrus and insula during diffusion-weighted magnetic resonance imaging (DW-MRI) on neurologically healthy adults. To date, cortical signal heterogeneity on DW images has not been investigated systematically. The purpose of our study was to determine whether there is regional signal variation in the brain cortices of neurologically healthy adults on DW-MR images. The SI of the cerebral cortices on DW-MR images at 1.5 T was evaluated in 50 neurologically healthy subjects (34 men, 16 women; age range 33-84 years; mean age 57.6 years). The cortical SI in the cingulate gyrus, insula, and temporal, occipital, and parietal lobes was graded relative to the SI of the frontal lobe. Contrast-to-noise ratios (CNRs) on DW-MR images were compared for each cortical area. Diffusion changes were analyzed by visually assessment of the differences in appearance among the cortices on apparent diffusion coefficient (ADC) maps. Increased SI was frequently seen in the cingulate gyrus and insula regardless of patient age. There were no significant gender- or laterality-related differences. The CNR was significantly higher in the cingulate gyrus and insula than in the other cortices (p <.01), and significant differences existed among the cortical regions (p <.001). There were no apparent ADC differences among the cortices on ADC maps. Regional signal variation of the brain cortices was observed on DW-MR images of healthy subjects, and the cingulate gyrus and insula frequently manifested high SI. These findings may help in the recognition of cortical signal abnormalities as visualized on DW-MR images. (orig.)

  10. Human cerebral cortices: signal variation on diffusion-weighted MR imaging

    International Nuclear Information System (INIS)

    Asao, Chiaki; Hirai, Toshinori; Yamashita, Yasuyuki; Yoshimatsu, Shunji; Matsukawa, Tetsuya; Imuta, Masanori; Sagara, Katsuro

    2008-01-01

    We have often encountered high signal intensity (SI) of the cingulate gyrus and insula during diffusion-weighted magnetic resonance imaging (DW-MRI) on neurologically healthy adults. To date, cortical signal heterogeneity on DW images has not been investigated systematically. The purpose of our study was to determine whether there is regional signal variation in the brain cortices of neurologically healthy adults on DW-MR images. The SI of the cerebral cortices on DW-MR images at 1.5 T was evaluated in 50 neurologically healthy subjects (34 men, 16 women; age range 33-84 years; mean age 57.6 years). The cortical SI in the cingulate gyrus, insula, and temporal, occipital, and parietal lobes was graded relative to the SI of the frontal lobe. Contrast-to-noise ratios (CNRs) on DW-MR images were compared for each cortical area. Diffusion changes were analyzed by visually assessment of the differences in appearance among the cortices on apparent diffusion coefficient (ADC) maps. Increased SI was frequently seen in the cingulate gyrus and insula regardless of patient age. There were no significant gender- or laterality-related differences. The CNR was significantly higher in the cingulate gyrus and insula than in the other cortices (p <.01), and significant differences existed among the cortical regions (p <.001). There were no apparent ADC differences among the cortices on ADC maps. Regional signal variation of the brain cortices was observed on DW-MR images of healthy subjects, and the cingulate gyrus and insula frequently manifested high SI. These findings may help in the recognition of cortical signal abnormalities as visualized on DW-MR images. (orig.)

  11. Brain activation in motor sequence learning is related to the level of native cortical excitability.

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    Silke Lissek

    Full Text Available Cortical excitability may be subject to changes through training and learning. Motor training can increase cortical excitability in motor cortex, and facilitation of motor cortical excitability has been shown to be positively correlated with improvements in performance in simple motor tasks. Thus cortical excitability may tentatively be considered as a marker of learning and use-dependent plasticity. Previous studies focused on changes in cortical excitability brought about by learning processes, however, the relation between native levels of cortical excitability on the one hand and brain activation and behavioral parameters on the other is as yet unknown. In the present study we investigated the role of differential native motor cortical excitability for learning a motor sequencing task with regard to post-training changes in excitability, behavioral performance and involvement of brain regions. Our motor task required our participants to reproduce and improvise over a pre-learned motor sequence. Over both task conditions, participants with low cortical excitability (CElo showed significantly higher BOLD activation in task-relevant brain regions than participants with high cortical excitability (CEhi. In contrast, CElo and CEhi groups did not exhibit differences in percentage of correct responses and improvisation level. Moreover, cortical excitability did not change significantly after learning and training in either group, with the exception of a significant decrease in facilitatory excitability in the CEhi group. The present data suggest that the native, unmanipulated level of cortical excitability is related to brain activation intensity, but not to performance quality. The higher BOLD mean signal intensity during the motor task might reflect a compensatory mechanism in CElo participants.

  12. Postnatal Ablation of Synaptic Retinoic Acid Signaling Impairs Cortical Information Processing and Sensory Discrimination in Mice.

    Science.gov (United States)

    Park, Esther; Tjia, Michelle; Zuo, Yi; Chen, Lu

    2018-06-06

    Retinoic acid (RA) and its receptors (RARs) are well established essential transcriptional regulators during embryonic development. Recent findings in cultured neurons identified an independent and critical post-transcriptional role of RA and RARα in the homeostatic regulation of excitatory and inhibitory synaptic transmission in mature neurons. However, the functional relevance of synaptic RA signaling in vivo has not been established. Here, using somatosensory cortex as a model system and the RARα conditional knock-out mouse as a tool, we applied multiple genetic manipulations to delete RARα postnatally in specific populations of cortical neurons, and asked whether synaptic RA signaling observed in cultured neurons is involved in cortical information processing in vivo Indeed, conditional ablation of RARα in mice via a CaMKIIα-Cre or a layer 5-Cre driver line or via somatosensory cortex-specific viral expression of Cre-recombinase impaired whisker-dependent texture discrimination, suggesting a critical requirement of RARα expression in L5 pyramidal neurons of somatosensory cortex for normal tactile sensory processing. Transcranial two-photon imaging revealed a significant increase in dendritic spine elimination on apical dendrites of somatosensory cortical layer 5 pyramidal neurons in these mice. Interestingly, the enhancement of spine elimination is whisker experience-dependent as whisker trimming rescued the spine elimination phenotype. Additionally, experiencing an enriched environment improved texture discrimination in RARα-deficient mice and reduced excessive spine pruning. Thus, RA signaling is essential for normal experience-dependent cortical circuit remodeling and sensory processing. SIGNIFICANCE STATEMENT The importance of synaptic RA signaling has been demonstrated in in vitro studies. However, whether RA signaling mediated by RARα contributes to neural circuit functions in vivo remains largely unknown. In this study, using a RARα conditional

  13. Event-related cortical processing in neuropathic pain under long-term spinal cord stimulation.

    Science.gov (United States)

    Weigel, Ralf; Capelle, H Holger; Flor, Herta; Krauss, Joachim K

    2015-01-01

    Several mechanisms were suggested in the past to explain the beneficial effect of spinal cord stimulation (SCS) in patients suffering from neuropathic pain. Little is known about potential supraspinal mechanisms. In this study cortical signaling of patients with neuropathic pain and successful long-term treatment with SCS was analyzed. Observational study. University hospital, neurosurgical department, outpatient clinic for movement disorders and pain, institute for cognitive and clinical neuroscience. Nine patients with neuropathic pain of a lower extremity with a lasting response to chronic SCS were included. Cortical activity was analyzed using event-related potentials of the electroencephalogram after non-painful and painful stimulation. Each patient was tested under the effect of long-term SCS and 24 hours after cessation of SCS. Cortical areas involved in the peaks of evoked potentials were localized using a source localization method based on a fixed dipole model. Detection threshold and intensity of non-painful stimulation did not differ significantly on both sides. Pain threshold was significantly lower on the neuropathic side under the effect of SCS (P = 0.03). Bilateral pain thresholds were significantly lower (P = 0.03 healthy side, P = 0.003 neuropathic side) in 5 patients with increased pain after cessation of SCS. Under the effect of SCS cortical negativities (N1, N2, N3) and positivities (P1) demonstrated bilaterally comparable amplitudes. After cessation of SCS, decreased threshold for peripheral stimulation resulted in lowered negativities on both sides. The positivity P1 was differentially regulated and was reduced more contralateral to the unaffected side. N2 was localized at the sensory representation of the leg within the homunculus. The main vector of P1 was localized within the cingular cortex (CC) and moved more anteriorly under the effect of SCS. The exact time span that SCS continues to have an effect is not known. However, due to patient

  14. Awake Craniotomy in Arteriovenous Malformation Surgery: The Usefulness of Cortical and Subcortical Mapping of Language Function in Selected Patients.

    Science.gov (United States)

    Gamble, Alexander J; Schaffer, Sarah G; Nardi, Dominic J; Chalif, David J; Katz, Jeffery; Dehdashti, Amir R

    2015-11-01

    Awake craniotomy for removal of intra-axial lesions is a well-established procedure. Few studies, however, have investigated the usefulness of this approach for resection of arteriovenous malformations adjacent to eloquent language areas. We demonstrate our experience by using cortical stimulation mapping and report for the first time on the usefulness of subcortical stimulation with interrogation of language function during resection of arteriovenous malformations (AVMs) located near language zones. Patients undergoing awake craniotomy for AVMs located in language zones and at least 5 mm away from the closest functional magnetic resonance imaging activation were analyzed. During surgery, cortical bipolar stimulation at 50 Hz, with an intensity of 2 mA, increased to a maximum of 10 mA was performed in the region around the AVM before claiming it negative for language function. In positive language site, the area was restimulated 3 times to confirm the functional deficit. The AVM resection was started based on cortical mapping findings. Further subcortical stimulation performed in concert with speech interrogation by the neuropsychologist continued at key points throughout the resection as feasible. The usefulness of cortical and subcortical stimulation in addition to patient outcomes was analyzed. Between March 2009 and September 2014, 42 brain AVM resections were performed. Four patients with left-sided language zone AVMs underwent awake craniotomy. The AVM locations were fronto-opercular in 2 patients and posterior temporal in 2. The AVM Spetzler-Martin grades were II (2 patients) and III (2 patients). In 1 patient, complete speech arrest was noticed during mapping of the peri-malformation zone, which was not breached during resection. In a second patient who initially demonstrated negative cortical mapping, a speech deficit was noticed during resection and subcortical stimulation. This guided the approach to protect and avoid the sensitive zone. This patient

  15. Hyperfixation of Tc-99m ECD in subacute cortical infarction

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    Kim, Jae Seung; Kweon, Sun Uck; Ryu, Jin Sook; Moon, Dae Hyuk; Lee, Hee Kyung [College of Medicine, Ulsan Univ., Seoul (Korea, Republic of)

    2001-07-01

    It has been known that hyperfixation of Tc-99m ECD (HF) is not shown in subacute cerebral infarction because the brain distribution of Tc-99m ECD reflects not only perfusion but also the metabolic status of brain tissue. However, we observed several cases with HF in the subacute pure cortical infarction. To find out the cause of HF in subacute cortical infarction. We assessed the difference in associated cerebral hemodynamics and clinical findings between the subacute cortical infarctions with and without HF. We reviewed 16 patients (63.8{+-}8.6 yr, M/F: 15/1) with pure cortical infarction not involving adjacent subcortical white matter on MRI. All patients underwent acetazolamide stress brain perfusion SPECT using Tc-99m ECD and MRI at subacute period (7.3{+-}4.4 days from ictus). Uptake of Tc-99m ECD in infarcted cortex was assessed visually comparing the contralateral side. To assess the difference in associate clinical findings between the infarctions with and without HF, rCVR of the cerebral territory including infarcted cortex, extent of Gd-enhancement on MRI. Intervals between SPECT and ictus, and the presence of associated ICA stenosis were evaluated. Infarctions were focal (n=8) or multifocal (n=8) and located in frontoparietal cortices on MRI. Twelve patients were accompanied with ipsilateral ICA stenosis. Resting SPECT showed increased cortical uptake (=HF) in 7 patients and decreased in 9. rCVR of the MCA territory was preserved in all of the 7 patients with HF, compared with 4 of the 9 patients without HF (p=0.03). Gd-enhancement was minimal in all of the 7 patients with HF, compared with of the 0 patients without HF (p=0.03). Presence of ipsilateral ICA stenosis and intervals from ictus were not different (p>0.1) Subacute cerebral cortical infarction with HF was more frequently associated with preserved rCVR and minimal destruction of the blood-brain barrier than that without HF. Our findings suggest that HF may result from luxury perfusion of

  16. Pharmacological Mechanisms of Cortical Enhancement Induced by the Repetitive Pairing of Visual/Cholinergic Stimulation.

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    Jun-Il Kang

    Full Text Available Repetitive visual training paired with electrical activation of cholinergic projections to the primary visual cortex (V1 induces long-term enhancement of cortical processing in response to the visual training stimulus. To better determine the receptor subtypes mediating this effect the selective pharmacological blockade of V1 nicotinic (nAChR, M1 and M2 muscarinic (mAChR or GABAergic A (GABAAR receptors was performed during the training session and visual evoked potentials (VEPs were recorded before and after training. The training session consisted of the exposure of awake, adult rats to an orientation-specific 0.12 CPD grating paired with an electrical stimulation of the basal forebrain for a duration of 1 week for 10 minutes per day. Pharmacological agents were infused intracortically during this period. The post-training VEP amplitude was significantly increased compared to the pre-training values for the trained spatial frequency and to adjacent spatial frequencies up to 0.3 CPD, suggesting a long-term increase of V1 sensitivity. This increase was totally blocked by the nAChR antagonist as well as by an M2 mAChR subtype and GABAAR antagonist. Moreover, administration of the M2 mAChR antagonist also significantly decreased the amplitude of the control VEPs, suggesting a suppressive effect on cortical responsiveness. However, the M1 mAChR antagonist blocked the increase of the VEP amplitude only for the high spatial frequency (0.3 CPD, suggesting that M1 role was limited to the spread of the enhancement effect to a higher spatial frequency. More generally, all the drugs used did block the VEP increase at 0.3 CPD. Further, use of each of the aforementioned receptor antagonists blocked training-induced changes in gamma and beta band oscillations. These findings demonstrate that visual training coupled with cholinergic stimulation improved perceptual sensitivity by enhancing cortical responsiveness in V1. This enhancement is mainly mediated by n

  17. Adrenal medullary regulation of rat renal cortical adrenergic receptors

    International Nuclear Information System (INIS)

    Sundaresan, P.R.; Guarnaccia, M.M.; Izzo, J.L. Jr.

    1987-01-01

    The role of the adrenal medulla in the regulation of renal cortical adrenergic receptors was investigated in renal cortical particular fractions from control rats and rats 6 wk after adrenal demedullation. The specific binding of [ 3 H]prazosin, [ 3 H]rauwolscine, and [ 125 I]iodocyanopindolol were used to quantitate α 1 -, α 2 -, and β-adrenergic receptors, respectively. Adrenal demedullation increased the concentration of all three groups of renal adrenergic receptors; maximal number of binding sites (B max , per milligram membrane protein) for α 1 -, and α 2 -, and β-adrenergic receptors were increased by 22, 18.5, and 25%, respectively. No differences were found in the equilibrium dissociation constants (K D ) for any of the radioligands. Plasma corticosterone and plasma and renal norepinephrine levels were unchanged, whereas plasma epinephrine was decreased 72% by adrenal demedullation, renal cortical epinephrine was not detectable in control or demedullated animals. The results suggest that, in the physiological state, the adrenal medulla modulates the number of renal cortical adrenergic receptors, presumably through the actions of a circulating factor such as epinephrine

  18. Characterization of Peripheral Activity States and Cortical Local Field Potentials of Mice in an Elevated Plus Maze Test.

    Science.gov (United States)

    Okonogi, Toya; Nakayama, Ryota; Sasaki, Takuya; Ikegaya, Yuji

    2018-01-01

    Elevated plus maze (EPM) tests have been used to assess animal anxiety levels. Little information is known regarding how physiological activity patterns of the brain-body system are altered during EPM tests. Herein, we monitored cortical local field potentials (LFPs), electrocardiograms (ECGs), electromyograms (EMGs), and respiratory signals in individual mice that were repeatedly exposed to EPM tests. On average, mouse heart rates were higher in open arms. In closed arms, the mice occasionally showed decreased heart and respiratory rates lasting for several seconds or minutes, characterized as low-peripheral activity states of peripheral signals. The low-activity states were observed only when the animals were in closed arms, and the frequencies of the states increased as the testing days proceeded. During the low-activity states, the delta and theta powers of cortical LFPs were significantly increased and decreased, respectively. These results demonstrate that cortical oscillations crucially depend on whether an animal exhibits low-activity states in peripheral organs rather than the EPM arm in which the animal is located. These results suggest that combining behavioral tests with physiological makers enables a more accurate evaluation of rodent mental states.

  19. Characterization of Peripheral Activity States and Cortical Local Field Potentials of Mice in an Elevated Plus Maze Test

    Directory of Open Access Journals (Sweden)

    Toya Okonogi

    2018-04-01

    Full Text Available Elevated plus maze (EPM tests have been used to assess animal anxiety levels. Little information is known regarding how physiological activity patterns of the brain-body system are altered during EPM tests. Herein, we monitored cortical local field potentials (LFPs, electrocardiograms (ECGs, electromyograms (EMGs, and respiratory signals in individual mice that were repeatedly exposed to EPM tests. On average, mouse heart rates were higher in open arms. In closed arms, the mice occasionally showed decreased heart and respiratory rates lasting for several seconds or minutes, characterized as low-peripheral activity states of peripheral signals. The low-activity states were observed only when the animals were in closed arms, and the frequencies of the states increased as the testing days proceeded. During the low-activity states, the delta and theta powers of cortical LFPs were significantly increased and decreased, respectively. These results demonstrate that cortical oscillations crucially depend on whether an animal exhibits low-activity states in peripheral organs rather than the EPM arm in which the animal is located. These results suggest that combining behavioral tests with physiological makers enables a more accurate evaluation of rodent mental states.

  20. Hypo-and hyperthyroidism affect the ATP, ADP and AMP hydrolysis in rat hippocampal and cortical slices.

    Science.gov (United States)

    Bruno, Alessandra Nejar; Diniz, Gabriela Placoná; Ricachenevsky, Felipe Klein; Pochmann, Daniela; Bonan, Carla Denise; Barreto-Chaves, Maria Luiza M; Sarkis, João José Freitas

    2005-05-01

    The presence of severe neurological symptoms in thyroid diseases has highlighted the importance of thyroid hormones in the normal functioning of the mature brain. Since, ATP is an important excitatory neurotransmitter and adenosine acts as a neuromodulatory structure inhibiting neurotransmitters release in the central nervous system (CNS), the ectonucleotidase cascade that hydrolyzes ATP to adenosine, is also involved in the control of brain functions. Thus, we investigated the influence of hyper-and hypothyroidism on the ATP, ADP and AMP hydrolysis in hippocampal and cortical slices from adult rats. Hyperthyroidism was induced by daily injections of l-thyroxine (T4) 25 microg/100 g body weight, for 14 days. Hypothyroidism was induced by thyroidectomy and methimazole (0.05%) added to their drinking water for 14 days. Hypothyroid rats were hormonally replaced by daily injections of T4 (5 microg/100 g body weight, i.p.) for 5 days. Hyperthyroidism significantly inhibited the ATP, ADP and AMP hydrolysis in hippocampal slices. In brain cortical slices, hyperthyroidism inhibited the AMP hydrolysis. In contrast, hypothyroidism increased the ATP, ADP and AMP hydrolysis in both hippocampal and cortical slices and these effects were reverted by T4 replacement. Furthermore, hypothyroidism increased the expression of NTPDase1 and 5'-nucleotidase, whereas hyperthyroidism decreased the expression of 5'-nucleotidase in hippocampus of adult rats. These findings demonstrate that thyroid disorders may influence the enzymes involved in the complete degradation of ATP to adenosine and possibly affects the responses mediated by adenine nucleotides in the CNS of adult rats.

  1. Calcium uptake and release by isolated cortices and microsomes from the unfertilized egg of the sea urchin strongylocentrotus droebachiensis

    International Nuclear Information System (INIS)

    Oberdorf, J.A.

    1986-01-01

    Two subcellular fractions of the sea urchin egg were studied for their potential role in regulating the transient rise in cytosolic calcium that accompanies fertilization. Isolated cortices from unfertilized sea urchin eggs sequester calcium in an ATP dependent manner when incubated in a medium containing free calcium levels characteristic of the resting cell. This ATP dependent calcium uptake activity, measured in the presence of 5mM Na Azide to prevent mitochondrial accumulation, was increased by oxalate, and was blocked by 150 μM quercetin and 50 μM vanadate. Cortices preloaded with 45 Ca in the presence of ATP dramatically increased their rate of calcium efflux upon the addition of (1) the calcium ionophore A23187 (10 μM), (2) trifluoperazine (200 μM), (3) concentrations of free calcium that activated cortical granule exocytosis, and (4) the calcium mobilizing agent inositol trisphosphate (IP3). This pool of calcium is most likely sequestered in the portion of the egg's endoplasmic reticulum (ER) that remains associated with the cortical region during its isolation. They have developed a method for obtaining a high yield of purified microsomal vesicles from whole eggs. This preparation also demonstrates ATP dependent calcium sequestering activity which increases in the presence of oxalate and has similar sensitivities to calcium transport inhibitors, however the isolated microsomal vesicles did not show any detectable release of calcium when exposed to IP3. Procedures originally developed for purifying calsequestrin were used to partially purify a 58,000 MW protein from the egg's microsomal vesicles

  2. SLEEP AND OLFACTORY CORTICAL PLASTICITY

    Directory of Open Access Journals (Sweden)

    Dylan eBarnes

    2014-04-01

    Full Text Available In many systems, sleep plays a vital role in memory consolidation and synaptic homeostasis. These processes together help store information of biological significance and reset synaptic circuits to facilitate acquisition of information in the future. In this review, we describe recent evidence of sleep-dependent changes in olfactory system structure and function which contribute to odor memory and perception. During slow-wave sleep, the piriform cortex becomes hypo-responsive to odor stimulation and instead displays sharp-wave activity similar to that observed within the hippocampal formation. Furthermore, the functional connectivity between the piriform cortex and other cortical and limbic regions is enhanced during slow-wave sleep compared to waking. This combination of conditions may allow odor memory consolidation to occur during a state of reduced external interference and facilitate association of odor memories with stored hedonic and contextual cues. Evidence consistent with sleep-dependent odor replay within olfactory cortical circuits is presented. These data suggest that both the strength and precision of odor memories is sleep-dependent. The work further emphasizes the critical role of synaptic plasticity and memory in not only odor memory but also basic odor perception. The work also suggests a possible link between sleep disturbances that are frequently co-morbid with a wide range of pathologies including Alzheimer’s disease, schizophrenia and depression and the known olfactory impairments associated with those disorders.

  3. A Cross-Sectional Study Demonstrating Increased Serum Amyloid A Related Inflammation in High-Density Lipoproteins from Subjects with Type 1 Diabetes Mellitus and How This Association Was Augmented by Poor Glycaemic Control

    Directory of Open Access Journals (Sweden)

    Jane McEneny

    2015-01-01

    Full Text Available Inflammatory atherosclerosis is increased in subjects with type 1 diabetes mellitus (T1DM. Normally high-density lipoproteins (HDL protect against atherosclerosis; however, in the presence of serum amyloid-A- (SAA- related inflammation this property may be reduced. Fasting blood was obtained from fifty subjects with T1DM, together with fifty age, gender and BMI matched control subjects. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Serum-hsCRP and serum-, HDL2-, and HDL3-SAA were measured by ELISAs. Compared to control subjects, SAA was increased in T1DM subjects, nonsignificantly in serum (P=0.088, and significantly in HDL2(P=0.003 and HDL3(P=0.005. When the T1DM group were separated according to mean HbA1c (8.34%, serum-SAA and HDL3-SAA levels were higher in the T1DM subjects with HbA1c ≥ 8.34%, compared to when HbA1c was 0.05. This cross-sectional study demonstrated increased SAA-related inflammation in subjects with T1DM that was augmented by poor glycaemic control. We suggest that SAA is a useful inflammatory biomarker in T1DM, which may contribute to their increased atherosclerosis risk.

  4. Premotor and Motor Cortices Encode Reward.

    Directory of Open Access Journals (Sweden)

    Pavan Ramkumar

    Full Text Available Rewards associated with actions are critical for motivation and learning about the consequences of one's actions on the world. The motor cortices are involved in planning and executing movements, but it is unclear whether they encode reward over and above limb kinematics and dynamics. Here, we report a categorical reward signal in dorsal premotor (PMd and primary motor (M1 neurons that corresponds to an increase in firing rates when a trial was not rewarded regardless of whether or not a reward was expected. We show that this signal is unrelated to error magnitude, reward prediction error, or other task confounds such as reward consumption, return reach plan, or kinematic differences across rewarded and unrewarded trials. The availability of reward information in motor cortex is crucial for theories of reward-based learning and motivational influences on actions.

  5. Osteocyte lacunar properties in rat cortical bone

    DEFF Research Database (Denmark)

    Bach-Gansmo, Fiona Linnea; Weaver, James C.; Jensen, Mads Hartmann

    2015-01-01

    Recently, the roles of osteocytes in bone maintenance have gained increasing attention. Osteocytes reside in lacunae that are interconnected by canaliculi resulting in a vast cellular network within the mineralized bone matrix. As the structure of the lacuno-canalicular network is highly connected......-species but also inter-site variation in lacunar properties. Here, osteocyte lacunae in rat cortical bone have been studied using synchrotron radiation micro computed tomography (SR μCT) and backscattered electron (BE) microscopy. Quantitative lacunar geometric characteristics are reported based on the synchrotron...... radiation data, differentiating between circumferential lamellar bone and a central, more disordered bone type. From these studies, no significant differences were found in lacunar volumes between lamellar and central bone, whereas significant differences in lacunar orientation, shape and density values...

  6. Low cortical bone density measured by computed tomography in children and adolescents with untreated hyperthyroidism.

    Science.gov (United States)

    Numbenjapon, Nawaporn; Costin, Gertrude; Gilsanz, Vicente; Pitukcheewanont, Pisit

    2007-05-01

    To determine whether increased thyroid hormones levels have an effect on various bone components (cortical vs cancellous bone). The anthropometric and 3-dimensional quantitative computed tomography (CT) bone measurements, including bone density (BD), cross-sectional area (CSA) of the lumbar spine and femur, and cortical bone area (CBA) of the femur, of 18 children and adolescents with untreated hyperthyroidism were reviewed and compared with those of age-, sex-, and ethnicity-matched historical controls. No significant differences in height, weight, body mass index (BMI), or pubertal staging between patients and controls were found. Cortical BD was significantly lower (P hyperthyroidism compared with historical controls. After adjusting for weight and height, no difference in femur CSA between hyperthyroid children and historical controls was evident. No significant correlations among thyroid hormone levels, antithyroid antibody levels, and cortical BD values were found. As determined by CT, cortical bone is the preferential site of bone loss in children and adolescents with untreated hyperthyroidism.

  7. Effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats.

    Science.gov (United States)

    Iwamoto, Jun; Matsumoto, Hideo; Takeda, Tsuyoshi; Sato, Yoshihiro; Yeh, James K

    2010-09-01

    The purpose of the present study was to examine the effects of vitamin K2 on cortical and cancellous bone mass, cortical osteocyte and lacunar system, and porosity in sciatic neurectomized rats. Thirty-four female Sprague-Dawley retired breeder rats were randomized into three groups: age-matched control, sciatic neurectomy (NX), and NX + vitamin K2 administration (menatetrenone, 30 mg/kg/day p.o., three times a week). At the end of the 8-week experiment, bone histomorphometric analysis was performed on cortical and cancellous bone of the tibial diaphysis and proximal metaphysis, respectively, and osteocyte lacunar system and porosity were evaluated on cortical bone of the tibial diaphysis. NX decreased cortical and cancellous bone mass compared with age-matched controls as a result of increased endocortical and trabecular bone erosion and decreased trabecular mineral apposition rate (MAR). Vitamin K2 ameliorated the NX-induced increase in bone erosion, prevented the NX-induced decrease in MAR, and increased bone formation rate (BFR/bone surface) in cancellous bone, resulting in an attenuation of NX-induced cancellous bone loss. However, vitamin K2 did not significantly influence cortical bone mass. NX also decreased osteocyte density and lacunar occupancy and increased porosity in cortical bone compared with age-matched controls. Vitamin K2 ameliorated the NX-induced decrease in lacunar occupancy by viable osteocytes and the NX-induced increase in porosity. The present study showed the efficacy of vitamin K2 for cancellous bone mass and cortical lacunar occupancy by viable osteocytes and porosity in sciatic NX rats.

  8. The stability of mandibular prognathism corrected by bilateral sagittal split osteotomies: a comparison of bi-cortical osteosynthesis and mono-cortical osteosynthesis.

    Science.gov (United States)

    Hsu, S S-P; Huang, C-S; Chen, P K-T; Ko, E W-C; Chen, Y-R

    2012-02-01

    This study evaluated the differences in surgical changes and post-surgical changes between bi-cortical and mono-cortical osteosynthesis (MCO) in the correction of skeletal Class III malocclusion with bilateral sagittal split osteotomies (BSSOs). Twenty-five patients had bi-cortical osteosynthesis (BCO), 32 patients had mono-cortical fixation. Lateral and postero-anterior cephalometric radiographs, taken at the time of surgery, before surgery, 1 month after surgery, and on completion of orthodontic treatment (mean 9.9 months after surgery), were obtained for evaluation. Cephalometric analysis and superimposition were used to investigate the surgical and post-surgical changes. Independent t-test was performed to compare the difference between the two groups. Pearson's correlations were tested to evaluate the factors related to the relapse of the mandible. The sagittal relapse rate was 20% in the bi-cortical and 25% in the mono-cortical group. The forward-upward rotation of the mandible in the post-surgical period contributed most of the sagittal relapse. There were no statistically significant differences in sagittal and vertical changes between the two groups during surgery and in the post-surgical period. No factors were found to correlate with post-surgical relapse, but the intergonial width increased more in the bi-cortical group. The study suggested that both methods of skeletal fixation had similar postoperative stability. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  9. Cortical morphology of adolescents with bipolar disorder and with schizophrenia.

    Science.gov (United States)

    Janssen, Joost; Alemán-Gómez, Yasser; Schnack, Hugo; Balaban, Evan; Pina-Camacho, Laura; Alfaro-Almagro, Fidel; Castro-Fornieles, Josefina; Otero, Soraya; Baeza, Inmaculada; Moreno, Dolores; Bargalló, Nuria; Parellada, Mara; Arango, Celso; Desco, Manuel

    2014-09-01

    Recent evidence points to overlapping decreases in cortical thickness and gyrification in the frontal lobe of patients with adult-onset schizophrenia and bipolar disorder with psychotic symptoms, but it is not clear if these findings generalize to patients with a disease onset during adolescence and what may be the mechanisms underlying a decrease in gyrification. This study analyzed cortical morphology using surface-based morphometry in 92 subjects (age range 11-18 years, 52 healthy controls and 40 adolescents with early-onset first-episode psychosis diagnosed with schizophrenia (n=20) or bipolar disorder with psychotic symptoms (n=20) based on a two year clinical follow up). Average lobar cortical thickness, surface area, gyrification index (GI) and sulcal width were compared between groups, and the relationship between the GI and sulcal width was assessed in the patient group. Both patients groups showed decreased cortical thickness and increased sulcal width in the frontal cortex when compared to healthy controls. The schizophrenia subgroup also had increased sulcal width in all other lobes. In the frontal cortex of the combined patient group sulcal width was negatively correlated (r=-0.58, padolescents with schizophrenia and bipolar disorder with psychotic symptoms there is cortical thinning, decreased GI and increased sulcal width of the frontal cortex present at the time of the first psychotic episode. Decreased frontal GI is associated with the widening of the frontal sulci which may reduce sulcal surface area. These results suggest that abnormal growth (or more pronounced shrinkage during adolescence) of the frontal cortex represents a shared endophenotype for psychosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Cortical thickness abnormalities associated with dyslexia, independent of remediation status

    Science.gov (United States)

    Ma, Yizhou; Koyama, Maki S.; Milham, Michael P.; Castellanos, F. Xavier; Quinn, Brian T.; Pardoe, Heath; Wang, Xiuyuan; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas; Blackmon, Karen

    2014-01-01

    Abnormalities in cortical structure are commonly observed in children with dyslexia in key regions of the “reading network.” Whether alteration in cortical features reflects pathology inherent to dyslexia or environmental influence (e.g., impoverished reading experience) remains unclear. To address this question, we compared MRI-derived metrics of cortical thickness (CT), surface area (SA), gray matter volume (GMV), and their lateralization across three different groups of children with a historical diagnosis of dyslexia, who varied in current reading level. We compared three dyslexia subgroups with: (1) persistent reading and spelling impairment; (2) remediated reading impairment (normal reading scores), and (3) remediated reading and spelling impairments (normal reading and spelling scores); and a control group of (4) typically developing children. All groups were matched for age, gender, handedness, and IQ. We hypothesized that the dyslexia group would show cortical abnormalities in regions of the reading network relative to controls, irrespective of remediation status. Such a finding would support that cortical abnormalities are inherent to dyslexia and are not a consequence of abnormal reading experience. Results revealed increased CT of the left fusiform gyrus in the dyslexia group relative to controls. Similarly, the dyslexia group showed CT increase of the right superior temporal gyrus, extending into the planum temporale, which resulted in a rightward CT asymmetry on lateralization indices. There were no group differences in SA, GMV, or their lateralization. These findings held true regardless of remediation status. Each reading level group showed the same “double hit” of atypically increased left fusiform CT and rightward superior temporal CT asymmetry. Thus, findings provide evidence that a developmental history of dyslexia is associated with CT abnormalities, independent of remediation status. PMID:25610779

  11. Suppression of autophagy in osteocytes does not modify the adverse effects of glucocorticoids on cortical bone.

    Science.gov (United States)

    Piemontese, Marilina; Onal, Melda; Xiong, Jinhu; Wang, Yiying; Almeida, Maria; Thostenson, Jeff D; Weinstein, Robert S; Manolagas, Stavros C; O'Brien, Charles A

    2015-06-01

    Glucocorticoid excess decreases bone mass and strength in part by acting directly on osteoblasts and osteocytes, but the mechanisms remain unclear. Macroautophagy (herein referred to as autophagy) is a lysosome-based recycling pathway that promotes the turnover of intracellular components and can promote cell function and survival under stressful conditions. Recent studies have shown that glucocorticoids stimulate autophagy in osteocytes, suggesting that autophagy may oppose the negative actions of glucocorticoids on this cell type. To address this possibility, we compared the impact of prednisolone administration on the skeletons of adult mice in which autophagy was suppressed in osteocytes, via deletion of Atg7 with a Dmp1-Cre transgene, to their control littermates. In control mice, prednisolone increased autophagic flux in osteocyte-enriched bone as measured by LC3 conversion, but this change did not occur in the mice lacking Atg7 in osteocytes. Nonetheless, prednisolone reduced femoral cortical thickness, increased cortical porosity, and reduced bone strength to similar extents in mice with and without autophagy in osteocytes. Prednisolone also suppressed osteoblast number and bone formation in the cancellous bone of control mice. As shown previously, Atg7 deletion in osteocytes reduced osteoblast number and bone formation in cancellous bone, but these parameters were not further reduced by prednisolone administration. In cortical bone, prednisolone elevated osteoclast number to a similar extent in both genotypes. Taken together, these results demonstrate that although glucocorticoids stimulate autophagy in osteocytes, suppression of autophagy in this cell type does not worsen the negative impact of glucocorticoids on the skeleton. Published by Elsevier Inc.

  12. Motor cortical plasticity in Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Kaviraja eUdupa

    2013-09-01

    Full Text Available In Parkinson’s disease (PD, there are alterations of the basal ganglia (BG thalamo-cortical networks, primarily due to degeneration of nigrostrial dopaminergic neurons. These changes in subcortical networks lead to plastic changes in primary motor cortex (M1, which mediates cortical motor output and is a potential target for treatment of PD. Studies investigating the motor cortical plasticity using non-invasive transcranial magnetic stimulation (TMS have found altered plasticity in PD, but there are inconsistencies among these studies. This is likely because plasticity depends on many factors such as the extent of dopaminergic loss and disease severity, response to dopaminergic replacement therapies, development of L-dopa-induced dyskinesias (LID, the plasticity protocol used, medication and stimulation status in patients treated with deep brain stimulation (DBS. The influences of LID and DBS on BG and M1 plasticity have been explored in animal models and in PD patients. In addition, many other factors such age, genetic factors (e.g. brain derived neurotropic factor and other neurotransmitters or receptors polymorphism, emotional state, time of the day, physical fitness have been documented to play role in the extent of plasticity induced by TMS in human studies. In this review, we summarize the studies that investigated M1 plasticity in PD and demonstrate how these afore-mentioned factors affect motor cortical plasticity in PD. We conclude that it is important to consider the clinical, demographic and technical factors that influence various plasticity protocols while developing these protocols as diagnostic or prognostic tools in PD. We also discuss how the modulation of cortical excitability and the plasticity with these non-invasive brain stimulation techniques facilitate the understanding of the pathophysiology of PD and help design potential therapeutic possibilities in this disorder.

  13. Value of renal cortical scintigraphy in children with acute pyelonephritis

    International Nuclear Information System (INIS)

    Paul, A.K.; Miah, M.S.R.; Rahman, H.A.; Hasan, M.H.

    2004-01-01

    Purpose: Acute pyelonephritis is a major cause of morbidity in children with urinary tract infection and can result in irreversible renal scarring leading to hypertension and end-stage renal disease. Tc-99m-dimercaptosuccinic acid (DMSA) scintigraphy is the imaging modality of choice for the detection of acute pyelonephhfis and renal scarfing. This study evaluated the importance of renal cortical scintigraphy to identify children at risk from renal damage due to acute pyelonephritis. Methods: Forty-nine children (ages 9 months to 11 years) with urinary tract infection having positive urine culture were studied. A DMSA scan was performed within 72 hours of receiving antibiotic during acute infection. Single or multiple areas of varying degrees of diminished cortical uptake or diffusely decreased uptake in an enlarged kidney was considered for the diagnosis of acute pyelonephrifis. Follow-up scintigraphy was done at 6 months of initial scan in children with acute pyelonephritis documented by DMSA scan. Renal scarring was considered if the affected kidney shows cortical thinning or focal cortical defect with loss of volume or become small kidney. Children with known renal tract abnormalities were excluded from the study. RESULTS: Twenty-seven children (55%) wine considered acute pyelonephritis by DMSA scintigraphy and the abnormality was bilateral in 17(63%) cases and unilateral in 10(37%) cases. Among these 44 abnormal kidneys, scintigraphy showed solitary defect in 29 kidneys, multiple defects in 6 kidneys and diffuse decreased uptake in 9 kidneys. Of them, twenty children were available for follow-up evaluation and scintigraphy demonstrated complete recovery in 21 of 34 (62%) kidneys and renal scarfing in 13 of 34 (38%) kidneys. Renal scarring was found in 5 of 7 kidneys (71%) with diffuse decreased uptake, 2 of 5 kidneys (40%) with multiple cortical defect and 6 of 22 (27%) with single focal detect. Conclusion: The scintigraphic pattern of acute pyelonephritis

  14. The effect of α-, β-adrenergic receptor agonists and antagonists of the efflux of 22Na and uptake of 42K by rat brain cortical slices

    International Nuclear Information System (INIS)

    Phillis, J.W.; Wu, P.H.; Thierry, D.L.

    1982-01-01

    The effects of norepinephrine on ion fluxes in rat brain cortical slices have now been ascertained. 22 Na efflux and 42 K influx are enhanced by norepinephrine. The increase in ion fluxes can be blocked by ouabain, phentolamine and propranolol, suggesting that the catecholamine activates a membrane sodium pump by a receptor-mediated step. The facilitation of 22 Na efflux is stereospecific as demonstrated by the very weak action of D-norepinephrine at 10 -5 M concentration. Various α-adrenergic and β-adrenergic receptor agonists, including oxymetazoline, naphazoline, clonidine, tramazoline, methoxamine, phenylephrine, L-isoproterenol and methoxyphenamine are potent stimulants of the sodium pump as demonstrated by their enhancement of ion fluxes in rat brain cortical slices. The results are consistent with the hypothesis that norepinephrine hyperpolarizes central neurons by activating an ouabain-sensitive, receptor-mediated sodium pump. (Auth.)

  15. RADIONUCLIDE IMAGING IN THE ASSESSMENT OF THE RESIDUAL CORTICAL FUNCTION OF OBSTRUCTIVE NEPHROPATHIES

    OpenAIRE

    川村, 寿一; 伊藤, 坦; 王, 本欽; 吉田, 修; 藤田, 透

    1980-01-01

    The diagnostic value of 99m-Tc-DMSA renal scintigraphy was assessed in 156 kidneys of 107 patients with a variety of obstructive nephropathies. DMSA renal cortical imaging well demonstrated morphological changes in the renal parenchyma around the dilated pelvocalyceal system. DMSA renal uptake, as a marker of cortical functioning mass, paralleled the grading of the hydronephrotic changes on IVP. DMSA renal scintigram well visualizes the residual functioning area in the renal parenchyma and DM...

  16. Adult Pilomyxoid Astrocytoma Mimicking a Cortical Brain Tumor: MR Imaging Findings

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jong Chang; Weon, Young Cheol; Suh, Jae Hee; Kim, Young; Hwang, Jae Cheol [Ulsan University Hospital, Ulsan (Korea, Republic of)

    2010-08-15

    A pilomyxoid astrocytoma (PMA) is a recently identified low-grade neoplasm that was previously classified as a pilocytic astrocytoma (PA), yet demonstrates unique histological features and more aggressive behavior. Although a PMA is generally a tumor of early childhood and typically occurs in the hypothalamic/chiasmatic region, it can mimic cortical tumors, especially in adults. We report the MR findings of a PMA presenting as a cortical brain tumor in an adult with neurofibromatosis 1 (NF1)

  17. Phosphorus magnetic resonance spectroscopy in malformations of cortical development

    Directory of Open Access Journals (Sweden)

    Celi Santos Andrade

    2013-07-01

    Full Text Available Introduction Malformations of cortical development (MCD result from disruptions in the dynamic process of cerebral corticogenesis and are important causes of epilepsy, motor deficits and cognitive impairment. Objectives The aim of this study was to evaluate phospholipids metabolism in vivo in a series of patients with epilepsy and MCD. Methods Thirty-seven patients with MCD and 31 control subjects were studied using three-dimensional phosphorus magnetic resonance spectroscopy (31P-MRS at a 3.0 T scanner. Quantification methods were applied to the following resonances: phosphoethanolamine (PE, phosphocholine (PC, glycerophosphoethanolamine (GPE, glycerophosphocholine (GPC, inorganic phosphate (Pi, phosphocreatine (PCr, and a-, b-, and g-adenosine triphosphate (ATP. The magnesium (Mg2+ levels and pH were calculated based on PCr, Pi and b-ATP chemical shifts. Results Compared to controls, the MCD lesions exhibited lower pH values and higher Mg2+ levels (p<0.05. The lesions also presented significant reduction of GPC and PDE, and an increased PME/PDE ratio. The otherwise normal appearing parenchyma also demonstrated lower pH values in the frontoparietal cortex and bilateral centrum semiovale. Conclusions Our data support the idea that metabolic impairments occur in the lesions of MCD, with propagation to remote normal appearing parenchyma. The results also suggest that there are membrane turnover disturbances in MCD lesions.

  18. Understanding age-induced cortical porosity in women

    DEFF Research Database (Denmark)

    Andreasen, Christina Møller; Delaisse, Jean-Marie; van der Eerden, Bram C J

    2018-01-01

    of a histomorphometric analysis of sections of iliac bone specimens from 35 women (age 16-78 years). Firstly, the study shows that the aging-induced cortical porosity reflects an increased pore size rather than an increased pore density. Secondly, it establishes a novel histomorphometric classification of the pores...... initiation of the subsequent bone formation. This article is protected by copyright. All rights reserved....

  19. Response of cortical bone to antiresorptive treatment

    DEFF Research Database (Denmark)

    Hyldstrup, Lars; Jørgensen, J T; Sørensen, T K

    2001-01-01

    of the spine, hip, and forearm. Longitudinal changes in bone densitometry were compared with changes captured by DXR: BMD evaluated by DXR (BMDDXR), cortical thickness of the second metacarpal (CTMC2), and porosity of cortical bone. The expected annual postmenopausal reduction in BMD in the control group...... treatment regimens used in the prevention of osteoporosis....

  20. GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation

    Directory of Open Access Journals (Sweden)

    Antonela Bonafina

    2018-03-01

    Full Text Available Summary: The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2, promoting neuronal differentiation. While GDNF leads to decreased proliferation of cultured cortical precursor cells, ablation of GFRα1 in glutamatergic cortical precursors enhances its proliferation. We show that GDNF treatment of CNPs promoted morphological differentiation even in the presence of the self-renewal-promoting factor, FGF2. Analysis of GFRα1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFRα1-expressing neurons. Together, these results indicate that GDNF/GFRα1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors. : In this article, Ledda and colleagues show that GDNF acting through its receptor GFRα1 plays a critical role in the maturation of cortical progenitors by counteracting FGF2 self-renewal activity on neural stem cells and promoting neuronal differentiation. Keywords: GDNF, GFRα1, cortical precursors, proliferation, postmitotic neurons, neuronal differentiation

  1. Cortical surface area and cortical thickness in the precuneus of adult humans.

    Science.gov (United States)

    Bruner, E; Román, F J; de la Cuétara, J M; Martin-Loeches, M; Colom, R

    2015-02-12

    The precuneus has received considerable attention in the last decade, because of its cognitive functions, its role as a central node of the brain networks, and its involvement in neurodegenerative processes. Paleoneurological studies suggested that form changes in the deep parietal areas represent a major character associated with the origin of the modern human brain morphology. A recent neuroanatomical survey based on shape analysis suggests that the proportions of the precuneus are also a determinant source of overall brain geometrical differences among adult individuals, influencing the brain spatial organization. Here, we evaluate the variation of cortical thickness and cortical surface area of the precuneus in a sample of adult humans, and their relation with geometry and cognition. Precuneal thickness and surface area are not correlated. There is a marked individual variation. The right precuneus is thinner and larger than the left one, but there are relevant fluctuating asymmetries, with only a modest correlation between the hemispheres. Males have a thicker cortex but differences in cortical area are not significant between sexes. The surface area of the precuneus shows a positive allometry with the brain surface area, although the correlation is modest. The dilation/contraction of the precuneus, described as a major factor of variability within adult humans, is associated with absolute increase/decrease of its surface, but not with variation in thickness. Precuneal thickness, precuneal surface area and precuneal morphology are not correlated with psychological factors such as intelligence, working memory, attention control, and processing speed, stressing further possible roles of this area in supporting default mode functions. Beyond gross morphology, the processes underlying the large phenotypic variation of the precuneus must be further investigated through specific cellular analyses, aimed at considering differences in cellular size, density

  2. Ultrasonically-induced electrical potentials in demineralized bovine cortical bone

    Science.gov (United States)

    Mori, Shunki; Makino, Taiki; Koyama, Daisuke; Takayanagi, Shinji; Yanagitani, Takahiko; Matsukawa, Mami

    2018-04-01

    While the low-intensity pulsed ultrasound technique has proved useful for healing of bone fractures, the ultrasound healing mechanism is not yet understood. To understand the initial physical effects of the ultrasound irradiation process on bone, we have studied the anisotropic piezoelectric properties of bone in the MHz range. Bone is known to be composed of collagen and hydroxyapatite (HAp) and shows strong elastic anisotropy. In this study, the effects of HAp on the piezoelectricity were investigated experimentally. To remove the HAp crystallites from the bovine cortical bone, demineralization was performed using ethylene diamine tetra-acetic acid (EDTA) solutions. To investigate the piezoelectricity, we have fabricated ultrasound transducers using the cortical bone or demineralized cortical bone. The induced electrical potentials due to the piezoelectricity were observed as the output of these transducers under pulsed ultrasound irradiation in the MHz range. The cortical bone transducer (before mineralization) showed anisotropic piezoelectric behavior. When the ultrasound irradiation was applied normal to the transducer surface, the observed induced electrical potentials had minimum values. The potential increased under off-axis ultrasound irradiation with changes in polarization. In the demineralized bone transducer case, however, the anisotropic behavior was not observed in the induced electrical potentials. These results therefore indicate that the HAp crystallites affect the piezoelectric characteristics of bone.

  3. Reduced cortical thickness associated with visceral fat and BMI

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    Ralf Veit

    2014-01-01

    Full Text Available Structural brain imaging studies have shown that obesity is associated with widespread reductions in gray matter (GM volume. Although the body mass index (BMI is an easily accessible anthropometric measure, substantial health problems are more related to specific body fat compartments, like visceral adipose tissue (VAT. We investigated cortical thickness measures in a group of 72 healthy subjects (BMI range 20–35 kg/m2, age range 19–50 years. Multiple regression analyses were performed using VAT and BMI as predictors and age, gender, total surface area and education as confounds. BMI and VAT were independently associated with reductions in cortical thickness in clusters comprising the left lateral occipital area, the left inferior temporal cortex, and the left precentral and inferior parietal area, while the right insula, the left fusiform gyrus and the right inferior temporal area showed a negative correlation with VAT only. In addition, we could show significant reductions in cortical thickness with increasing VAT adjusted for BMI in the left temporal cortex. We were able to detect widespread cortical thinning in a young to middle-aged population related to BMI and VAT; these findings show close resemblance to studies focusing on GM volume differences in diabetic patients. This may point to the influence of VAT related adverse effects, like low-grade inflammation, as a potentially harmful factor on brain integrity already in individuals at risk of developing diabetes, metabolic syndromes and arteriosclerosis.

  4. Influence of cortical endplates on ultrasonic properties of trabecular bone

    International Nuclear Information System (INIS)

    Kim, Yoon Mi; Lee, Kang Il

    2015-01-01

    The present study investigated the influence of thick cortical endplates on the ultrasonic properties of trabecular bone in a femur with a high fracture risk. Twelve trabecular bone samples were prepared from bovine femurs, and acrylic plates with thicknesses of 1.25, 1.80, and 2.75 mm were manufactured to simulate the cortical endplates using acrylic with a density and a sound speed similar to cortical bone. Although the thickness of the acrylic plates attached to the two sides of the trabecular bone increased, high correlations were observed between the speed of sound and the apparent bone density of the trabecular bone, with Pearson's correlation coefficients of 0.80-0.86. High correlations were also observed between the attenuation coefficient at 0.5 mm and the apparent bone density of the trabecular bone, with Pearson's correlation coefficients of 0.84-0.91. These results suggest that the speed of sound and attenuation coefficient at a specific frequency measured in a femur with relatively thick cortical endplates compared to the calcaneus could be used as indices for predicting the bone mineral density of the femur.

  5. Prepulse Inhibition of Auditory Cortical Responses in the Caudolateral Superior Temporal Gyrus in Macaca mulatta.

    Science.gov (United States)

    Chen, Zuyue; Parkkonen, Lauri; Wei, Jingkuan; Dong, Jin-Run; Ma, Yuanye; Carlson, Synnöve

    2018-04-01

    Prepulse inhibition (PPI) refers to a decreased response to a startling stimulus when another weaker stimulus precedes it. Most PPI studies have focused on the physiological startle reflex and fewer have reported the PPI of cortical responses. We recorded local field potentials (LFPs) in four monkeys and investigated whether the PPI of auditory cortical responses (alpha, beta, and gamma oscillations and evoked potentials) can be demonstrated in the caudolateral belt of the superior temporal gyrus (STGcb). We also investigated whether the presence of a conspecific, which draws attention away from the auditory stimuli, affects the PPI of auditory cortical responses. The PPI paradigm consisted of Pulse-only and Prepulse + Pulse trials that were presented randomly while the monkey was alone (ALONE) and while another monkey was present in the same room (ACCOMP). The LFPs to the Pulse were significantly suppressed by the Prepulse thus, demonstrating PPI of cortical responses in the STGcb. The PPI-related inhibition of the N1 amplitude of the evoked responses and cortical oscillations to the Pulse were not affected by the presence of a conspecific. In contrast, gamma oscillations and the amplitude of the N1 response to Pulse-only were suppressed in the ACCOMP condition compared to the ALONE condition. These findings demonstrate PPI in the monkey STGcb and suggest that the PPI of auditory cortical responses in the monkey STGcb is a pre-attentive inhibitory process that is independent of attentional modulation.

  6. Motor-cortical interaction in Gilles de la Tourette syndrome.

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    Stephanie Franzkowiak

    Full Text Available BACKGROUND: In Gilles de la Tourette syndrome (GTS increased activation of the primary motor cortex (M1 before and during movement execution followed by increased inhibition after movement termination was reported. The present study aimed at investigating, whether this activation pattern is due to altered functional interaction between motor cortical areas. METHODOLOGY/PRINCIPAL FINDINGS: 10 GTS-patients and 10 control subjects performed a self-paced finger movement task while neuromagnetic brain activity was recorded using Magnetoencephalography (MEG. Cerebro-cerebral coherence as a measure of functional interaction was calculated. During movement preparation and execution coherence between contralateral M1 and supplementary motor area (SMA was significantly increased at beta-frequency in GTS-patients. After movement termination no significant differences between groups were evident. CONCLUSIONS/SIGNIFICANCE: The present data suggest that increased M1 activation in GTS-patients might be due to increased functional interaction between SMA and M1 most likely reflecting a pathophysiological marker of GTS. The data extend previous findings of motor-cortical alterations in GTS by showing that local activation changes are associated with alterations of functional networks between premotor and primary motor areas. Interestingly enough, alterations were evident during preparation and execution of voluntary movements, which implies a general theme of increased motor-cortical interaction in GTS.

  7. Perceptual learning and adult cortical plasticity.

    Science.gov (United States)

    Gilbert, Charles D; Li, Wu; Piech, Valentin

    2009-06-15

    The visual cortex retains the capacity for experience-dependent changes, or plasticity, of cortical function and cortical circuitry, throughout life. These changes constitute the mechanism of perceptual learning in normal visual experience and in recovery of function after CNS damage. Such plasticity can be seen at multiple stages in the visual pathway, including primary visual cortex. The manifestation of the functional changes associated with perceptual learning involve both long term modification of cortical circuits during the course of learning, and short term dynamics in the functional properties of cortical neurons. These dynamics are subject to top-down influences of attention, expectation and perceptual task. As a consequence, each cortical area is an adaptive processor, altering its function in accordance to immediate perceptual demands.

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

    Science.gov (United States)

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

    2003-04-01

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

  9. Effect of anxiety on cortical cerebral blood flow and metabolism

    International Nuclear Information System (INIS)

    Gur, R.C.; Gur, R.E.; Resnick, S.M.; Skolnick, B.E.; Alavi, A.; Reivich, M.

    1987-01-01

    The relation between anxiety and cortical activity was compared in two samples of normal volunteers. One group was studied with the noninvasive xenon-133 inhalation technique for measuring cerebral blood flow (CBF) and the other with positron emission tomography (PET) using 18 Flurodeoxyglucose ( 18 FDG) for measuring cerebral metabolic rates (CMR) for glucose. The inhalation technique produced less anxiety than the PET procedure, and for low anxiety subjects, there was a linear increase in CBF with anxiety. For higher anxiety subjects, however, there was a linear decrease in CBF with increased anxiety. The PET group manifested a linear decrease in CMR with increased anxiety. The results indicate that anxiety can have systematic effects on cortical activity, and this should be taken into consideration when comparing data from different procedures. They also suggest a physiologic explanation of a fundamental behavioral law that stipulates a curvilinear, inverted-U relationship between anxiety and performance

  10. The Unique Brain Anatomy of Meditation Practitioners: Alterations in Cortical Gyrification

    Science.gov (United States)

    Luders, Eileen; Kurth, Florian; Mayer, Emeran A.; Toga, Arthur W.; Narr, Katherine L.; Gaser, Christian

    2012-01-01

    Several cortical regions are reported to vary in meditation practitioners. However, prior analyses have focused primarily on examining gray matter or cortical thickness. Thus, additional effects with respect to other cortical features might have remained undetected. Gyrification (the pattern and degree of cortical folding) is an important cerebral characteristic related to the geometry of the brain’s surface. Thus, exploring cortical gyrification in long-term meditators may provide additional clues with respect to the underlying anatomical correlates of meditation. This study examined cortical gyrification in a large sample (n = 100) of meditators and controls, carefully matched for sex and age. Cortical gyrification was established by calculating mean curvature across thousands of vertices on individual cortical surface models. Pronounced group differences indicating larger gyrification in meditators were evident within the left precentral gyrus, right fusiform gyrus, right cuneus, as well as left and right anterior dorsal insula (the latter representing the global significance maximum). Positive correlations between gyrification and the number of meditation years were similarly pronounced in the right anterior dorsal insula. Although the exact functional implications of larger cortical gyrification remain to be established, these findings suggest the insula to be a key structure involved in aspects of meditation. For example, variations in insular complexity could affect the regulation of well-known distractions in the process of meditation, such as daydreaming, mind-wandering, and projections into past or future. Moreover, given that meditators are masters in introspection, awareness, and emotional control, increased insular gyrification may reflect an integration of autonomic, affective, and cognitive processes. Due to the cross-sectional nature of this study, further research is necessary to determine the relative contribution of nature and nurture to

  11. The Right Hemisphere Planum Temporale Supports Enhanced Visual Motion Detection Ability in Deaf People: Evidence from Cortical Thickness.

    Science.gov (United States)

    Shiell, Martha M; Champoux, François; Zatorre, Robert J

    2016-01-01

    After sensory loss, the deprived cortex can reorganize to process information from the remaining modalities, a phenomenon known as cross-modal reorganization. In blind people this cross-modal processing supports compensatory behavioural enhancements in the nondeprived modalities. Deaf people also show some compensatory visual enhancements, but a direct relationship between these abilities and cross-modally reorganized auditory cortex has only been established in an animal model, the congenitally deaf cat, and not in humans. Using T1-weighted magnetic resonance imaging, we measured cortical thickness in the planum temporale, Heschl's gyrus and sulcus, the middle temporal area MT+, and the calcarine sulcus, in early-deaf persons. We tested for a correlation between this measure and visual motion detection thresholds, a visual function where deaf people show enhancements as compared to hearing. We found that the cortical thickness of a region in the right hemisphere planum temporale, typically an auditory region, was greater in deaf individuals with better visual motion detection thresholds. This same region has previously been implicated in functional imaging studies as important for functional reorganization. The structure-behaviour correlation observed here demonstrates this area's involvement in compensatory vision and indicates an anatomical correlate, increased cortical thickness, of cross-modal plasticity.

  12. The Fas/Fas ligand death receptor pathway contributes to phenylalanine-induced apoptosis in cortical neurons.

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    Xiaodong Huang

    Full Text Available Phenylketonuria (PKU, an autosomal recessive disorder of amino acid metabolism caused by mutations in the phenylalanine hydroxylase (PAH gene, leads to childhood mental retardation by exposing neurons to cytotoxic levels of phenylalanine (Phe. A recent study showed that the mitochondria-mediated (intrinsic apoptotic pathway is involved in Phe-induced apoptosis in cultured cortical neurons, but it is not known if the death receptor (extrinsic apoptotic pathway and endoplasmic reticulum (ER stress-associated apoptosis also contribute to neurodegeneration in PKU. To answer this question, we used specific inhibitors to block each apoptotic pathway in cortical neurons under neurotoxic levels of Phe. The caspase-8 inhibitor Z-IETD-FMK strongly attenuated apoptosis in Phe-treated neurons (0.9 mM, 18 h, suggesting involvement of the Fas receptor (FasR-mediated cell death receptor pathway in Phe toxicity. In addition, Phe significantly increased cell surface Fas expression and formation of the Fas/FasL complex. Blocking Fas/FasL signaling using an anti-Fas antibody markedly inhibited apoptosis caused by Phe. In contrast, blocking the ER stress-induced cell death pathway with salubrinal had no effect on apoptosis in Phe-treated cortical neurons. These experiments demonstrate that the Fas death receptor pathway contributes to Phe-induced apoptosis and suggest that inhibition of the death receptor pathway may be a novel target for neuroprotection in PKU patients.

  13. Cortical thinning in cognitively normal elderly cohort of 60 to 89 year old from AIBL database and vulnerable brain areas

    Science.gov (United States)

    Lin, Zhongmin S.; Avinash, Gopal; Yan, Litao; McMillan, Kathryn

    2014-03-01

    Age-related cortical thinning has been studied by many researchers using quantitative MR images for the past three decades and vastly differing results have been reported. Although results have shown age-related cortical thickening in elderly cohort statistically in some brain regions under certain conditions, cortical thinning in elderly cohort requires further systematic investigation. This paper leverages our previously reported brain surface intensity model (BSIM)1 based technique to measure cortical thickness to study cortical changes due to normal aging. We measured cortical thickness of cognitively normal persons from 60 to 89 years old using Australian Imaging Biomarkers and Lifestyle Study (AIBL) data. MRI brains of 56 healthy people including 29 women and 27 men were selected. We measured average cortical thickness of each individual in eight brain regions: parietal, frontal, temporal, occipital, visual, sensory motor, medial frontal and medial parietal. Unlike the previous published studies, our results showed consistent age-related thinning of cerebral cortex in all brain regions. The parietal, medial frontal and medial parietal showed fastest thinning rates of 0.14, 0.12 and 0.10 mm/decade respectively while the visual region showed the slowest thinning rate of 0.05 mm/decade. In sensorimotor and parietal areas, women showed higher thinning (0.09 and 0.16 mm/decade) than men while in all other regions men showed higher thinning than women. We also created high resolution cortical thinning rate maps of the cohort and compared them to typical patterns of PET metabolic reduction of moderate AD and frontotemporal dementia (FTD). The results seemed to indicate vulnerable areas of cortical deterioration that may lead to brain dementia. These results validate our cortical thickness measurement technique by demonstrating the consistency of the cortical thinning and prediction of cortical deterioration trend with AIBL database.

  14. Long-term exposure to noise impairs cortical sound processing and attention control.

    Science.gov (United States)

    Kujala, Teija; Shtyrov, Yury; Winkler, Istvan; Saher, Marieke; Tervaniemi, Mari; Sallinen, Mikael; Teder-Sälejärvi, Wolfgang; Alho, Kimmo; Reinikainen, Kalevi; Näätänen, Risto

    2004-11-01

    Long-term exposure to noise impairs human health, causing pathological changes in the inner ear as well as other anatomical and physiological deficits. Numerous individuals are daily exposed to excessive noise. However, there is a lack of systematic research on the effects of noise on cortical function. Here we report data showing that long-term exposure to noise has a persistent effect on central auditory processing and leads to concurrent behavioral deficits. We found that speech-sound discrimination was impaired in noise-exposed individuals, as indicated by behavioral responses and the mismatch negativity brain response. Furthermore, irrelevant sounds increased the distractibility of the noise-exposed subjects, which was shown by increased interference in task performance and aberrant brain responses. These results demonstrate that long-term exposure to noise has long-lasting detrimental effects on central auditory processing and attention control.

  15. Microstructure of transcallosal motor fibers reflects type of cortical (re-)organization in congenital hemiparesis.

    Science.gov (United States)

    Juenger, Hendrik; Koerte, Inga K; Muehlmann, Marc; Mayinger, Michael; Mall, Volker; Krägeloh-Mann, Ingeborg; Shenton, Martha E; Berweck, Steffen; Staudt, Martin; Heinen, Florian

    2014-11-01

    Early unilateral brain lesions can lead to different types of corticospinal (re-)organization of motor networks. In one group of patients, the contralesional hemisphere exerts motor control not only over the contralateral non-paretic hand but also over the (ipsilateral) paretic hand, as the primary motor cortex is (re-)organized in the contralesional hemisphere. Another group of patients with early unilateral lesions shows "normal" contralateral motor projections starting in the lesioned hemisphere. We investigated how these different patterns of cortical (re-)organization affect interhemispheric transcallosal connectivity in patients with congenital hemiparesis. Eight patients with ipsilateral motor projections (group IPSI) versus 7 patients with contralateral motor projections (group CONTRA) underwent magnetic resonance diffusion tensor imaging (DTI). The corpus callosum (CC) was subdivided in 5 areas (I-V) in the mid-sagittal slice and volumetric information. The following diffusion parameters were calculated: fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD). DTI revealed significantly lower FA, increased trace and RD for group IPSI compared to group CONTRA in area III of the corpus callosum, where transcallosal motor fibers cross the CC. In the directly neighboring area IV, where transcallosal somatosensory fibers cross the CC, no differences were found for these DTI parameters between IPSI and CONTRA. Volume of callosal subsections showed significant differences for area II (connecting premotor cortices) and III, where group IPSI had lower volume. The results of this study demonstrate that the callosal microstructure in patients with congenital hemiparesis reflects the type of cortical (re-)organization. Early lesions disrupting corticospinal motor projections to the paretic hand consecutively affect the development or maintenance of transcallosal motor fibers. Copyright © 2014 European Paediatric Neurology Society

  16. Altered Cortical Activation in Adolescents With Acute Migraine: A Magnetoencephalography Study

    Science.gov (United States)

    Xiang, Jing; deGrauw, Xinyao; Korostenskaja, Milena; Korman, Abraham M.; O’Brien, Hope L.; Kabbouche, Marielle A.; Powers, Scott W.; Hershey, Andrew D.

    2013-01-01

    To quantitatively assess cortical dysfunction in pediatric migraine, 31 adolescents with acute migraine and age- and gender-matched controls were studied using a magnetoencephalography (MEG) system at a sampling rate of 6,000 Hz. Neuromagnetic brain activation was elicited by a finger-tapping task. The spectral and spatial signatures of magnetoencephalography data in 5 to 2,884 Hz were analyzed using Morlet wavelet and beamformers. Compared with controls, 31 migraine subjects during their headache attack phases (ictal) showed significantly prolonged latencies of neuromagnetic activation in 5 to 30 Hz, increased spectral power in 100 to 200 Hz, and a higher likelihood of neuromagnetic activation in the supplementary motor area, the occipital and ipsilateral sensorimotor cortices, in 2,200 to 2,800 Hz. Of the 31 migraine subjects, 16 migraine subjects during their headache-free phases (interictal) showed that there were no significant differences between interictal and control MEG data except that interictal spectral power in 100 to 200 Hz was significantly decreased. The results demonstrated that migraine subjects had significantly aberrant ictal brain activation, which can normalize interictally. The spread of abnormal ictal brain activation in both low- and high-frequency ranges triggered by movements may play a key role in the cascade of migraine attacks. Perspective This is the first study focusing on the spectral and spatial signatures of cortical dysfunction in adolescents with migraine using MEG signals in a frequency range of 5 to 2,884 Hz. This analyzing aberrant brain activation may be important for developing new therapeutic interventions for migraine in the future. PMID:23792072

  17. Competition and convergence between auditory and cross-modal visual inputs to primary auditory cortical areas

    Science.gov (United States)

    Mao, Yu-Ting; Hua, Tian-Miao

    2011-01-01

    Sensory neocortex is capable of considerable plasticity after sensory deprivation or damage to input pathways, especially early in development. Although plasticity can often be restorative, sometimes novel, ectopic inputs invade the affected cortical area. Invading inputs from other sensory modalities may compromise the original function or even take over, imposing a new function and preventing recovery. Using ferrets whose retinal axons were rerouted into auditory thalamus at birth, we were able to examine the effect of varying the degree of ectopic, cross-modal input on reorganization of developing auditory cortex. In particular, we assayed whether the invading visual inputs and the existing auditory inputs competed for or shared postsynaptic targets and whether the convergence of input modalities would induce multisensory processing. We demonstrate that although the cross-modal inputs create new visual neurons in auditory cortex, some auditory processing remains. The degree of damage to auditory input to the medial geniculate nucleus was directly related to the proportion of visual neurons in auditory cortex, suggesting that the visual and residual auditory inputs compete for cortical territory. Visual neurons were not segregated from auditory neurons but shared target space even on individual target cells, substantially increasing the proportion of multisensory neurons. Thus spatial convergence of visual and auditory input modalities may be sufficient to expand multisensory representations. Together these findings argue that early, patterned visual activity does not drive segregation of visual and auditory afferents and suggest that auditory function might be compromised by converging visual inputs. These results indicate possible ways in which multisensory cortical areas may form during development and evolution. They also suggest that rehabilitative strategies designed to promote recovery of function after sensory deprivation or damage need to take into

  18. Micro-computed tomography of fatigue microdamage in cortical bone using a barium sulfate contrast agent.

    Science.gov (United States)

    Leng, Huijie; Wang, Xiang; Ross, Ryan D; Niebur, Glen L; Roeder, Ryan K

    2008-01-01

    Accumulation of microdamage during fatigue can lead to increased fracture susceptibility in bone. Current techniques for imaging microdamage in bone are inherently destructive and two-dimensional. Therefore, the objective of this study was to image the accumulation of fatigue microdamage in cortical bone using micro-computed tomography (micro-CT) with a barium sulfate (BaSO(4)) contrast agent. Two symmetric notches were machined on the tensile surface of bovine cortical bone beams in order to generate damage ahead of the stress concentrations during four-point bending fatigue. Specimens were loaded to a specified number of cycles or until one notch fractured, such that the other notch exhibited the accumulation of microdamage prior to fracture. Microdamage ahead of the notch was stained in vitro by precipitation of BaSO(4) and imaged using micro-CT. Reconstructed images showed a distinct region of bright voxels around the notch tip or along propagating cracks due to the presence of BaSO(4), which was verified by backscattered electron imaging and energy dispersive spectroscopy. The shape of the stained region ahead of the notch tip was consistent with principal strain contours calculated by finite element analysis. The relative volume of the stained region was correlated with the number of loading cycles by non-linear regression using a power-law. This study demonstrates new methods for the non-destructive and three-dimensional detection of fatigue microdamage accumulation in cortical bone in vitro, which may be useful to gain further understanding into the role of microdamage in bone fragility.

  19. Prenatal exposure to arsenic impairs behavioral flexibility and cortical structure in mice

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    Kyaw Htet eAung

    2016-03-01

    Full Text Available Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although it has been demonstrated that exposure to sodium arsenite (NaAsO2 suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO2 impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO2 exposure on the behavior of mice in adulthood, and evaluated histological changes in the prelimbic cortex (PrL, which is a part of the medial prefrontal cortex that is critically involved in cognition. Drinking water with or without NaAsO2 (85 ppm was provided to pregnant C3H mice from gestational days 8 to 18, and offspring of both sexes were subjected to cognitive behavioral analyses at 60 weeks of age. The brains of female offspring were subsequently harvested and used for morphometrical analyses. We found that both male and female mice prenatally exposed to NaAsO2 displayed an impaired adaptation to repetitive reversal tasks. In morphometrical analyses of Nissl- or Golgi-stained tissue sections, we found that NaAsO2 exposure was associated with a significant increase in the number of pyramidal neurons in layers V and VI of the PrL, but not other layers of the PrL. More strikingly, prenatal NaAsO2 exposure was associated with a significant decrease in neurite length but not dendrite spine density in all layers of the PrL. Taken together, our results indicate that prenatal exposure to NaAsO2 leads to behavioral inflexibility in adulthood and cortical disarrangement in the PrL might contribute to this behavioral impairment.

  20. Histomorphometry and cortical robusticity of the adult human femur.

    Science.gov (United States)

    Miszkiewicz, Justyna Jolanta; Mahoney, Patrick

    2018-01-13

    Recent quantitative analyses of human bone microanatomy, as well as theoretical models that propose bone microstructure and gross anatomical associations, have started to reveal insights into biological links that may facilitate remodeling processes. However, relationships between bone size and the underlying cortical bone histology remain largely unexplored. The goal of this study is to determine the extent to which static indicators of bone remodeling and vascularity, measured using histomorphometric techniques, relate to femoral midshaft cortical width and robusticity. Using previously published and new quantitative data from 450 adult human male (n = 233) and female (n = 217) femora, we determine if these aspects of femoral size relate to bone microanatomy. Scaling relationships are explored and interpreted within the context of tissue form and function. Analyses revealed that the area and diameter of Haversian canals and secondary osteons, and densities of secondary osteons and osteocyte lacunae from the sub-periosteal region of the posterior midshaft femur cortex were significantly, but not consistently, associated with femoral size. Cortical width and bone robusticity were correlated with osteocyte lacunae density and scaled with positive allometry. Diameter and area of osteons and Haversian canals decreased as the width of cortex and bone robusticity increased, revealing a negative allometric relationship. These results indicate that microscopic products of cortical bone remodeling and vascularity are linked to femur size. Allometric relationships between more robust human femora with thicker cortical bone and histological products of bone remodeling correspond with principles of bone functional adaptation. Future studies may benefit from exploring scaling relationships between bone histomorphometric data and measurements of bone macrostructure.

  1. Cortical hypermetabolism in MCI subjects: a compensatory mechanism?

    International Nuclear Information System (INIS)

    Ashraf, A.; Fan, Z.; Brooks, D.J.; Edison, P.

    2015-01-01

    Alzheimer's disease (AD) is associated with amyloid accumulation that takes place decades before symptoms appear. Cognitive impairment in AD is associated with reduced glucose metabolism. However, neuronal plasticity/compensatory mechanisms might come into play before the onset of dementia. The aim of this study was to determine whether there is evidence of cortical hypermetabolism as a compensatory mechanism before amyloid deposition takes place in subjects with amnestic mild cognitive impairment (aMCI). Nine AD subjects and ten aMCI subjects had both [ 11 C]PIB and [ 18 F]FDG PET scans with arterial input in order to quantify the amyloid deposition and glucose metabolism in vivo in comparison with healthy control subjects who underwent either [ 11 C]PIB or [ 18 F]FDG PET scans. The [ 11 C]PIB PET scans were quantified using [ 11 C]PIB target region to cerebellum uptake ratio images created by integrating the activity collected from 60 to 90 min, and regional cerebral glucose metabolism was quantified using spectral analysis. In MCI subjects, cortical hypermetabolism was observed in four amyloid-negative subjects and one amyloid-positive subject, while hypometabolism was seen in five other MCI subjects with high amyloid load. Subjects with hypermetabolism and low amyloid did not convert to AD during clinical follow-up for 18 months in contrast to four amyloid-positive hypometabolic subjects who did convert to AD. This preliminary study suggests that compensatory hypermetabolism can occur in aMCI subjects, particularly in those who are amyloid-negative. The increase in metabolic rate in different cortical regions with predominance in the occipital cortex may be a compensatory response to the neuronal damage occurring early in the disease process. It may also reflect recruitment of relatively minimally affected cortical regions to compensate for reduced function in the temporoparietal cortical association areas. (orig.)

  2. Cortical hypermetabolism in MCI subjects: a compensatory mechanism?

    Energy Technology Data Exchange (ETDEWEB)

    Ashraf, A.; Fan, Z.; Brooks, D.J.; Edison, P. [Imperial College London, Neurology Imaging Unit, Division of Brain Sciences, London (United Kingdom)

    2014-09-30

    Alzheimer's disease (AD) is associated with amyloid accumulation that takes place decades before symptoms appear. Cognitive impairment in AD is associated with reduced glucose metabolism. However, neuronal plasticity/compensatory mechanisms might come into play before the onset of dementia. The aim of this study was to determine whether there is evidence of cortical hypermetabolism as a compensatory mechanism before amyloid deposition takes place in subjects with amnestic mild cognitive impairment (aMCI). Nine AD subjects and ten aMCI subjects had both [{sup 11}C]PIB and [{sup 18}F]FDG PET scans with arterial input in order to quantify the amyloid deposition and glucose metabolism in vivo in comparison with healthy control subjects who underwent either [{sup 11}C]PIB or [{sup 18}F]FDG PET scans. The [{sup 11}C]PIB PET scans were quantified using [{sup 11}C]PIB target region to cerebellum uptake ratio images created by integrating the activity collected from 60 to 90 min, and regional cerebral glucose metabolism was quantified using spectral analysis. In MCI subjects, cortical hypermetabolism was observed in four amyloid-negative subjects and one amyloid-positive subject, while hypometabolism was seen in five other MCI subjects with high amyloid load. Subjects with hypermetabolism and low amyloid did not convert to AD during clinical follow-up for 18 months in contrast to four amyloid-positive hypometabolic subjects who did convert to AD. This preliminary study suggests that compensatory hypermetabolism can occur in aMCI subjects, particularly in those who are amyloid-negative. The increase in metabolic rate in different cortical regions with predominance in the occipital cortex may be a compensatory response to the neuronal damage occurring early in the disease process. It may also reflect recruitment of relatively minimally affected cortical regions to compensate for reduced function in the temporoparietal cortical association areas. (orig.)

  3. Obstructive sleep apnea and cortical thickness in females and males.

    Science.gov (United States)

    Macey, Paul M; Haris, Natasha; Kumar, Rajesh; Thomas, M Albert; Woo, Mary A; Harper, Ronald M

    2018-01-01

    Obstructive sleep apnea (OSA) affects approximately 10% of adults, and alters brain gray and white matter. Psychological and physiological symptoms of the disorder are sex-specific, perhaps related to greater injury occurs in female than male patients in white matter. Our objective was to identify influences of OSA separated by sex on cortical gray matter. We assessed cortical thickness in 48 mild-severe OSA patients (mean age±std[range] = 46.5±9.0[30.8-62.7] years; apnea-hypopnea index = 32.6±21.1[6-102] events/hour; 12 female, 36 male; OSA severity: 5 mild, 18 moderate, 25 severe) and 62 controls (mean age = 47.7±8.9[30.9-65.8] years; 22 female, 40 male). All OSA patients were recently-diagnosed via polysomnography, and control subjects screened and a subset assessed with sleep studies. We used high-resolution magnetic resonance imaging to identify OSA-related cortical thinning, based on a model with condition and sex as independent variables. OSA and OSA-by-sex interaction effects were assessed (Pfrontal lobe in female OSA vs. all other groups. Significant thinning within the pre- and post-central gyri and the superior temporal gyrus, extending into the insula, appeared between the general OSA populations vs. control subjects. No areas showed increased thickness in OSA vs. controls or positive female OSA interaction effects. Reduced cortical thickness likely represents tissue atrophy from long term injury, including death of neurons and supporting glia from repeated intermittent hypoxic exposure in OSA, although disease comordities may also contribute to thinning. Lack of polysomnography in all control subjects means results may be confounded by undiagnosed OSA. The greater cortical injury in cognitive areas of female OSA patients may underlie enhanced symptoms in that group. The thinning associated with OSA in male and females OSA patients may contribute to autonomic dysregulation and impaired upper airway sensori-motor function.

  4. Cortical volumes and atrophy rates in FTD-3 CHMP2B mutation carriers and related non-carriers

    DEFF Research Database (Denmark)

    Eskildsen, Simon F; Østergaard, Lasse R; Rodell, Anders B

    2008-01-01

    with a mean interval of 16 months and surface based cortical segmentation we measured cortical thickness and volume, and quantified atrophy rates. Cortical thickness and atrophy rates were averaged within major lobes and focal effects were determined by parametric statistical maps. The volumetric atrophy...... in the frontal and occipital lobes, and in the left temporal lobe. Results indicated that cortical thickness has a higher sensitivity for detecting small changes than whole-brain volumetric measures. Comparing mutation carriers with non-carriers revealed increased atrophy rates in mutation carriers bilaterally...

  5. Verbal memory impairments in schizophrenia associated with cortical thinning

    Directory of Open Access Journals (Sweden)

    S. Guimond

    2016-01-01

    Full Text Available Verbal memory (VM represents one of the most affected cognitive domains in schizophrenia. Multiple studies have shown that schizophrenia is associated with cortical abnormalities, but it remains unclear whether these are related to VM impairments. Considering the vast literature demonstrating the role of the frontal cortex, the parahippocampal cortex, and the hippocampus in VM, we examined the cortical thickness/volume of these regions. We used a categorical approach whereby 27 schizophrenia patients with ‘moderate to severe’ VM impairments were compared to 23 patients with ‘low to mild’ VM impairments and 23 healthy controls. A series of between-group vertex-wise GLM on cortical thickness were performed for specific regions of interest defining the parahippocampal gyrus and the frontal cortex. When compared to healthy controls, patients with ‘moderate to severe’ VM impairments revealed significantly thinner cortex in the left frontal lobe, and the parahippocampal gyri. When compared to patients with ‘low to mild’ VM impairments, patients with ‘moderate to severe’ VM impairments showed a trend of thinner cortex in similar regions. Virtually no differences were observed in the frontal area of patients with ‘low to mild’ VM impairments relative to controls. No significant group differences were observed in the hippocampus. Our results indicate that patients with greater VM impairments demonstrate significant cortical thinning in regions known to be important in VM performance. Treating VM deficits in schizophrenia could have a positive effect on the brain; thus, subgroups of patients with more severe VM deficits should be a prioritized target in the development of new cognitive treatments.

  6. The effect of surface demineralization of cortical bone allograft on the properties of recombinant adeno-associated virus coatings.

    Science.gov (United States)

    Yazici, Cemal; Yanoso, Laura; Xie, Chao; Reynolds, David G; Samulski, R Jude; Samulski, Jade; Yannariello-Brown, Judith; Gertzman, Arthur A; Zhang, Xinping; Awad, Hani A; Schwarz, Edward M

    2008-10-01

    Freeze-dried recombinant adeno-associated virus (rAAV) coated structural allografts have emerged as an approach to engender necrotic cortical bone with host factors that will persist for weeks following surgery to facilitate revascularization, osteointegration, and remodeling. However, one major limitation is the nonporous cortical surface that prohibits uniform distribution of the rAAV coating prior to freeze-drying. To overcome this we have developed a demineralization method to increase surface absorbance while retaining the structural integrity of the allograft. Demineralized bone wafers (DBW) made from human femoral allograft rings demonstrated a significant 21.1% (73.6+/-3.9% versus 52.5+/-2.6%; pcoating versus mineralized controls. Co-incubation of rAAV-luciferase (rAAV-Luc) coated DBW with a monolayer of C3H10T1/2 cells in culture led to peak luciferase levels that were not significantly different from soluble rAAV-Luc controls (p>0.05), although the peaks occurred at 60h and 12h, respectively. To assess the transduction efficiency of rAAV-Luc coated DBW in vivo, we first performed a dose response with allografts containing 10(7), 10(9) or 10(10) particles that were surgically implanted into the quadriceps of mice, and assayed by in vivo bioluminescence imaging (BLI) on days 1, 3, 5, 7, 10, 14, and 21. The results demonstrated a dose response in which the DBW coated with 10(10) rAAV-Luc particles achieved peak gene expression levels on day 3, which persisted until day 21, and was significantly greater than the 10(7) dose throughout this time period (pcoated with 10(10) rAAV-Luc particles failed to demonstrate any significant differences in transduction kinetics or efficiency in vivo. Thus, surface demineralization of human cortical bone allograft increases its absorbance for uniform rAAV coating, without affecting vector transduction efficiency.

  7. Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

    Science.gov (United States)

    Pacheco-Costa, Rafael; Davis, Hannah M.; Sorenson, Chad; Hon, Mary C.; Hassan, Iraj; Reginato, Rejane D.; Allen, Matthew R.; Bellido, Teresita; Plotkin, Lilian I.

    2015-01-01

    Connexin43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43ΔCT/fl) were studied. Cx43ΔCT/fl mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43fl/fl controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43ΔCT is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43ΔCT mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43ΔCT were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. PMID:26409319

  8. Cortical feedback control of olfactory bulb circuits.

    Science.gov (United States)

    Boyd, Alison M; Sturgill, James F; Poo, Cindy; Isaacson, Jeffry S

    2012-12-20

    Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Neuroprotective effect of Quince leaf hydroalcoholic extract on intracerebroventricular streptozotocin-induced oxidative stress in cortical tissue of rat brain

    Directory of Open Access Journals (Sweden)

    A Hajizadeh Moghaddam

    2015-12-01

    Full Text Available Background & aim: Oxidative stress is a result of the imbalance between free radicals and the antioxidant system of the body. Increased oxidative stress in brain causes dysfunction of brain activities, destruction of neurons, and disease such as Alzheimer. Antioxidants, for example vitamins, phenolic compounds and flavonoids have been extensively investigated as potential therapeutic agents in vitro and in vivo for prevention of neurodegenerative diseases. In the present experimental study, the neuro-protective effect of quince leaf hydroalcoholic extract (QLHE on intracerebroventricular streptozotocin (icv-STZ-induced oxidative stress in cortical tissue of rat brain was examined. Methods: In the present experimental research, forty-two Wistar rats were randomly divided into control, sham, icv-STZ and icv-STZ treated with QLHE groups. The ICV-STZ group rats were injected unilaterally with ICV-STZ (3 mg/kg using a stereotactic device and QLHE (50, 100 and 150 mg/kg/day were administered for 6 weeks starting from 3 weeks before of ICV-STZ injection. The rats were killed at the end of the study and their brain cortical tissue superoxide dismutase and catalase activity were measured. The assay of catalase and superoxide dismutase was performed by following the Genet method. The amount of protein was determined according to the Bradford method.The statistical analysis was performed using one way ANOVA. Data were expressed as mean±SD and  P<0.05 was considered significant. Results: The present study indicated that in the ICV-STZ group showed significant decrease (P<0.001 in enzymatic antioxidants superoxide dismutase and catalase in the cortical tissue of the brain. Treatment of different doses of QLHE significantly increased superoxide dismutase and catalase activity compared to icv-STZ group (P<0.001 in cortical tissue of the brain. Conclusion: The study demonstrated the effectiveness of quince leaf hydroalcoholic extract as a powerful antioxidant

  10. Stereotypic wheel running decreases cortical activity in mice

    Science.gov (United States)

    Fisher, Simon P.; Cui, Nanyi; McKillop, Laura E.; Gemignani, Jessica; Bannerman, David M.; Oliver, Peter L.; Peirson, Stuart N.; Vyazovskiy, Vladyslav V.

    2016-01-01

    Prolonged wakefulness is thought to gradually increase ‘sleep need' and influence subsequent sleep duration and intensity, but the role of specific waking behaviours remains unclear. Here we report the effect of voluntary wheel running during wakefulness on neuronal activity in the motor and somatosensory cortex in mice. We find that stereotypic wheel running is associated with a substantial reduction in firing rates among a large subpopulation of cortical neurons, especially at high speeds. Wheel running also has longer-term effects on spiking activity across periods of wakefulness. Specifically, cortical firing rates are significantly higher towards the end of a spontaneous prolonged waking period. However, this increase is abolished when wakefulness is dominated by running wheel activity. These findings indicate that wake-related changes in firing rates are determined not only by wake duration, but also by specific waking behaviours. PMID:27748455

  11. Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study.

    Science.gov (United States)

    Holschneider, Daniel P; Wang, Zhuo; Pang, Raina D

    2014-01-01

    Rodent cortical midline structures (CMS) are involved in emotional, cognitive and attentional processes. Tract tracing has revealed complex patterns of structural connectivity demonstrating connectivity-based integration and segregation for the prelimbic, cingulate area 1, retrosplenial dysgranular cortices dorsally, and infralimbic, cingulate area 2, and retrosplenial granular cortices ventrally. Understanding of CMS functional connectivity (FC) remains more limited. Here we present the first subregion-level FC analysis of the mouse CMS, and assess whether fear results in state-dependent FC changes analogous to what has been reported in humans. Brain mapping using [(14)C]-iodoantipyrine was performed in mice during auditory-cued fear conditioned recall and in controls. Regional cerebral blood flow (CBF) was analyzed in 3-D images reconstructed from brain autoradiographs. Regions-of-interest were selected along the CMS anterior-posterior and dorsal-ventral axes. In controls, pairwise correlation and graph theoretical analyses showed strong FC within each CMS structure, strong FC along the dorsal-ventral axis, with segregation of anterior from posterior structures. Seed correlation showed FC of anterior regions to limbic/paralimbic areas, and FC of posterior regions to sensory areas-findings consistent with functional segregation noted in humans. Fear recall increased FC between the cingulate and retrosplenial cortices, but decreased FC between dorsal and ventral structures. In agreement with reports in humans, fear recall broadened FC of anterior structures to the amygdala and to somatosensory areas, suggesting integration and processing of both limbic and sensory information. Organizational principles learned from animal models at the mesoscopic level (brain regions and pathways) will not only critically inform future work at the microscopic (single neurons and synapses) level, but also have translational value to advance our understanding of human brain

  12. Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study

    Directory of Open Access Journals (Sweden)

    Daniel P Holschneider

    2014-06-01

    Full Text Available Rodent cortical midline structures (CMS are involved in emotional, cognitive and attentional processes. Tract tracing has revealed complex patterns of structural connectivity demonstrating connectivity-based integration and segregation for the prelimbic, cingulate area 1, retrosplenial dysgranular cortices dorsally, and infralimbic, cingulate area 2, and retrosplenial granular cortices ventrally. Understanding of CMS functional connectivity (FC remains more limited. Here we present the first subregion-level FC analysis of the mouse CMS, and assess whether fear results in state-dependent FC changes analogous to what has been reported in humans. Brain mapping using [14C]-iodoantipyrine was performed in mice during auditory-cued fear conditioned recall and in controls. Regional cerebral blood flow was analyzed in 3-D images reconstructed from brain autoradiographs. Regions-of-interest were selected along the CMS anterior-posterior and dorsal-ventral axes. In controls, pairwise correlation and graph theoretical analyses showed strong FC within each CMS structure, strong FC along the dorsal-ventral axis, with segregation of anterior from posterior structures. Seed correlation showed FC of anterior regions to limbic/paralimbic areas, and FC of posterior regions to sensory areas--findings consistent with functional segregation noted in humans. Fear recall increased FC between the cingulate and retrosplenial cortices, but decreased FC between dorsal and ventral structures. In agreement with reports in humans, fear recall broadened FC of anterior structures to the amygdala and to somatosensory areas, suggesting integration and processing of both limbic and sensory information. Organizational principles learned from animal models at the mesoscopic level (brain regions and pathways will not only critically inform future work at the microscopic (single neurons and synapses level, but also have translational value to advance our understanding of human brain

  13. Cortical heterotopia in Aicardi's syndrome - CT findings

    International Nuclear Information System (INIS)

    Besenski, N.; Bosnjak, V.; Ligutic, I.; Marusic-Della Marina, B.

    1988-01-01

    The case of 5-month-old female infant with Aicardi's syndrome is presented. The main clinical features were severe developmental retardation and intractable epileptic seizures. Ophthalmoscopic examination revealed pathognomonic choriorethinopathy. Ultrasonic examination of the brain detected agenesis of the corpus callosum, whereas CT showed a coexisting malformation of the brain, i.e. cortical heterotopia of the gray matter. Agenesis of the corpus callosum is an entity well-recognized by sonography. However, ultrasonography is an insufficient modality for the visualization of cortical heterotopia which is common to all cases of Aicardi's syndrome. Therefore, in cases of suspected Aicardi's syndrome CT is recommended, as it enables the diagnosis of cortical heterotopia. (orig.)

  14. Connectivities and synchronous firing in cortical neuronal networks

    International Nuclear Information System (INIS)

    Jia, L.C.; Sano, M.; Lai, P.-Y.; Chan, C.K.

    2004-01-01

    Network connectivities (k-bar) of cortical neural cultures are studied by synchronized firing and determined from measured correlations between fluorescence intensities of firing neurons. The bursting frequency (f) during synchronized firing of the networks is found to be an increasing function of k-bar. With f taken to be proportional to k-bar, a simple random model with a k-bar dependent connection probability p(k-bar) has been constructed to explain our experimental findings successfully

  15. Cortical plasticity associated with Braille learning.

    Science.gov (United States)

    Hamilton, R H; Pascual-Leone, A

    1998-05-01

    Blind subjects who learn to read Braille must acquire the ability to extract spatial information from subtle tactile stimuli. In order to accomplish this, neuroplastic changes appear to take place. During Braille learning, the sensorimotor cortical area devoted to the representation of the reading finger enlarges. This enlargement follows a two-step process that can be demonstrated with transcranial magnetic stimulation mapping and suggests initial unmasking of existing connections and eventual establishment of more stable structural changes. In addition, Braille learning appears to be associated with the recruitment of parts of the occipital, formerly `visual', cortex (V1 and V2) for tactile information processing. In blind, proficient Braille readers, the occipital cortex can be shown not only to be associated with tactile Braille reading but also to be critical for reading accuracy. Recent studies suggest the possibility of applying non-invasive neurophysiological techniques to guide and improve functional outcomes of these plastic changes. Such interventions might provide a means of accelerating functional adjustment to blindness.

  16. Facilitating text reading in posterior cortical atrophy.

    Science.gov (United States)

    Yong, Keir X X; Rajdev, Kishan; Shakespeare, Timothy J; Leff, Alexander P; Crutch, Sebastian J

    2015-07-28

    We report (1) the quantitative investigation of text reading in posterior cortical atrophy (PCA), and (2) the effects of 2 novel software-based reading aids that result in dramatic improvements in the reading ability of patients with PCA. Reading performance, eye movements, and fixations were assessed in patients with PCA and typical Alzheimer disease and in healthy controls (experiment 1). Two reading aids (single- and double-word) were evaluated based on the notion that reducing the spatial and oculomotor demands of text reading might support reading in PCA (experiment 2). Mean reading accuracy in patients with PCA was significantly worse (57%) compared with both patients with typical Alzheimer disease (98%) and healthy controls (99%); spatial aspects of passages were the primary determinants of text reading ability in PCA. Both aids led to considerable gains in reading accuracy (PCA mean reading accuracy: single-word reading aid = 96%; individual patient improvement range: 6%-270%) and self-rated measures of reading. Data suggest a greater efficiency of fixations and eye movements under the single-word reading aid in patients with PCA. These findings demonstrate how neurologic characterization of a neurodegenerative syndrome (PCA) and detailed cognitive analysis of an important everyday skill (reading) can combine to yield aids capable of supporting important everyday functional abilities. This study provides Class III evidence that for patients with PCA, 2 software-based reading aids (single-word and double-word) improve reading accuracy. © 2015 American Academy of Neurology.

  17. Pitch perception prior to cortical maturation

    Science.gov (United States)

    Lau, Bonnie K.

    Pitch perception plays an important role in many complex auditory tasks including speech perception, music perception, and sound source segregation. Because of the protracted and extensive development of the human auditory cortex, pitch perception might be expected to mature, at least over the first few months of life. This dissertation investigates complex pitch perception in 3-month-olds, 7-month-olds and adults -- time points when the organization of the auditory pathway is distinctly different. Using an observer-based psychophysical procedure, a series of four studies were conducted to determine whether infants (1) discriminate the pitch of harmonic complex tones, (2) discriminate the pitch of unresolved harmonics, (3) discriminate the pitch of missing fundamental melodies, and (4) have comparable sensitivity to pitch and spectral changes as adult listeners. The stimuli used in these studies were harmonic complex tones, with energy missing at the fundamental frequency. Infants at both three and seven months of age discriminated the pitch of missing fundamental complexes composed of resolved and unresolved harmonics as well as missing fundamental melodies, demonstrating perception of complex pitch by three months of age. More surprisingly, infants in both age groups had lower pitch and spectral discrimination thresholds than adult listeners. Furthermore, no differences in performance on any of the tasks presented were observed between infants at three and seven months of age. These results suggest that subcortical processing is not only sufficient to support pitch perception prior to cortical maturation, but provides adult-like sensitivity to pitch by three months.

  18. Facilitating text reading in posterior cortical atrophy

    Science.gov (United States)

    Rajdev, Kishan; Shakespeare, Timothy J.; Leff, Alexander P.; Crutch, Sebastian J.

    2015-01-01

    Objective: We report (1) the quantitative investigation of text reading in posterior cortical atrophy (PCA), and (2) the effects of 2 novel software-based reading aids that result in dramatic improvements in the reading ability of patients with PCA. Methods: Reading performance, eye movements, and fixations were assessed in patients with PCA and typical Alzheimer disease and in healthy controls (experiment 1). Two reading aids (single- and double-word) were evaluated based on the notion that reducing the spatial and oculomotor demands of text reading might support reading in PCA (experiment 2). Results: Mean reading accuracy in patients with PCA was significantly worse (57%) compared with both patients with typical Alzheimer disease (98%) and healthy controls (99%); spatial aspects of passages were the primary determinants of text reading ability in PCA. Both aids led to considerable gains in reading accuracy (PCA mean reading accuracy: single-word reading aid = 96%; individual patient improvement range: 6%–270%) and self-rated measures of reading. Data suggest a greater efficiency of fixations and eye movements under the single-word reading aid in patients with PCA. Conclusions: These findings demonstrate how neurologic characterization of a neurodegenerative syndrome (PCA) and detailed cognitive analysis of an important everyday skill (reading) can combine to yield aids capable of supporting important everyday functional abilities. Classification of evidence: This study provides Class III evidence that for patients with PCA, 2 software-based reading aids (single-word and double-word) improve reading accuracy. PMID:26138948

  19. Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

    Science.gov (United States)

    Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

    2011-03-01

    Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

  20. Early MR detection of cortical and subcortical hypoxic-ischemic encephalopathy in full-term-infants

    International Nuclear Information System (INIS)

    Christophe, C.; Clercx, A.; Blum, D.; Hasaerts, D.; Segebarth, C.; Perlmutter, N.

    1994-01-01

    Four observations illustrate the potential of MR imaging in the early depiction of multiple types of neuropathologic lesions which may coexist in the full-term newborn, upon severe hypoxic-ischemic encephalopathy (HIE). In particular, diffuse, postnatal involvement of cerebral cortex and subcortical white matter (WM) is demonstrated. Cortical hyperintensity on both proton-density- and T1-weighted images is probably related to cellular necrosis which is distributed diffusely or parasigattally. Hyperintense, frontal, subcortical WM edging on proton-density-weighted images results from the increase of water concentration, induced either by infract or by edema. Diffuse WM areas of low intensity on T1-weighted images and of high intensity on T2-weighted images are presumably related to cytotoxic and/or vasogenic edema, proportional to the underlying damaged tissues. On follow-up MR examinations, several months later, the importance of cortical atrophy and of the myelination delay appeared related to the importance of the lesions detected during the post-natal period. (orig.)

  1. Mapping cortical haemodynamics during neonatal seizures using diffuse optical tomography: A case study

    Directory of Open Access Journals (Sweden)

    Harsimrat Singh

    2014-01-01

    Full Text Available Seizures in the newborn brain represent a major challenge to neonatal medicine. Neonatal seizures are poorly classified, under-diagnosed, difficult to treat and are associated with poor neurodevelopmental outcome. Video-EEG is the current gold-standard approach for seizure detection and monitoring. Interpreting neonatal EEG requires expertise and the impact of seizures on the developing brain remains poorly understood. In this case study we present the first ever images of the haemodynamic impact of seizures on the human infant brain, obtained using simultaneous diffuse optical tomography (DOT and video-EEG with whole-scalp coverage. Seven discrete periods of ictal electrographic activity were observed during a 60 minute recording of an infant with hypoxic–ischaemic encephalopathy. The resulting DOT images show a remarkably consistent, high-amplitude, biphasic pattern of changes in cortical blood volume and oxygenation in response to each electrographic event. While there is spatial variation across the cortex, the dominant haemodynamic response to seizure activity consists of an initial increase in cortical blood volume prior to a large and extended decrease typically lasting several minutes. This case study demonstrates the wealth of physiologically and clinically relevant information that DOT–EEG techniques can yield. The consistency and scale of the haemodynamic responses observed here also suggest that DOT–EEG has the potential to provide improved detection of neonatal seizures.

  2. Cortical drive of low-frequency oscillations in the human nucleus accumbens during action selection.

    Science.gov (United States)

    Stenner, Max-Philipp; Litvak, Vladimir; Rutledge, Robb B; Zaehle, Tino; Schmitt, Friedhelm C; Voges, Jürgen; Heinze, Hans-Jochen; Dolan, Raymond J

    2015-07-01

    The nucleus accumbens is thought to contribute to action selection by integrating behaviorally relevant information from multiple regions, including prefrontal cortex. Studies in rodents suggest that information flow to the nucleus accumbens may be regulated via task-dependent oscillatory coupling between regions. During instrumental behavior, local field potentials (LFP) in the rat nucleus accumbens and prefrontal cortex are coupled at delta frequencies (Gruber AJ, Hussain RJ, O'Donnell P. PLoS One 4: e5062, 2009), possibly mediating suppression of afferent input from other areas and thereby supporting cortical control (Calhoon GG, O'Donnell P. Neuron 78: 181-190, 2013). In this report, we demonstrate low-frequency cortico-accumbens coupling in humans, both at rest and during a decision-making task. We recorded LFP from the nucleus accumbens in six epilepsy patients who underwent implantation of deep brain stimulation electrodes. All patients showed significant coherence and phase-synchronization between LFP and surface EEG at delta and low theta frequencies. Although the direction of this coupling as indexed by Granger causality varied between subjects in the resting-state data, all patients showed a cortical drive of the nucleus accumbens during action selection in a decision-making task. In three patients this was accompanied by a significant coherence increase over baseline. Our results suggest that low-frequency cortico-accumbens coupling represents a highly conserved regulatory mechanism for action selection. Copyright © 2015 the American Physiological Society.

  3. Microtubule bundling plays a role in ethylene-mediated cortical microtubule reorientation in etiolated Arabidopsis hypocotyls.

    Science.gov (United States)

    Ma, Qianqian; Sun, Jingbo; Mao, Tonglin

    2016-05-15

    The gaseous hormone ethylene is known to regulate plant growth under etiolated conditions (the 'triple response'). Although organization of cortical microtubules is essential for cell elongation, the underlying mechanisms that regulate microtubule organization by hormone signaling, including ethylene, are ambiguous. In the present study, we demonstrate that ethylene signaling participates in regulation of cortical microtubule reorientation. In particular, regulation of microtubule bundling is important for this process in etiolated hypocotyls. Time-lapse analysis indicated that selective stabilization of microtubule-bundling structures formed in various arrays is related to ethylene-mediated microtubule orientation. Bundling events and bundle growth lifetimes were significantly increased in oblique and longitudinal arrays, but decreased in transverse arrays in wild-type cells in response to ethylene. However, the effects of ethylene on microtubule bundling were partially suppressed in a microtubule-bundling protein WDL5 knockout mutant (wdl5-1). This study suggests that modulation of microtubule bundles that have formed in certain orientations plays a role in reorienting microtubule arrays in response to ethylene-mediated etiolated hypocotyl cell elongation. © 2016. Published by The Company of Biologists Ltd.

  4. Familial temporal lobe epilepsy due to focal cortical dysplasia type IIIa.

    Science.gov (United States)

    Fabera, Petr; Krijtova, Hana; Tomasek, Martin; Krysl, David; Zamecnik, Josef; Mohapl, Milan; Jiruska, Premysl; Marusic, Petr

    2015-09-01

    Focal cortical dysplasia (FCD) represents a common cause of refractory epilepsy. It is considered a sporadic disorder, but its occasional familial occurrence suggests the involvement of genetic mechanisms. Siblings with intractable epilepsy were referred for epilepsy surgery evaluation. Both patients were examined using video-EEG monitoring, MRI examination and PET imaging. They underwent left anteromedial temporal lobe resection. Electroclinical features pointed to left temporal lobe epilepsy and MRI examination revealed typical signs of left-sided hippocampal sclerosis and increased white matter signal intensity in the left temporal pole. PET examination confirmed interictal hypometabolism in the left temporal lobe. Histopathological examination of resected tissue demonstrated the presence FCD type IIIa, i.e. hippocampal sclerosis and focal cortical dysplasia in the left temporal pole. We present a unique case of refractory mesial temporal lobe epilepsy in siblings, characterized by an identical clinical profile and histopathology of FCD type IIIa, who were successfully treated by epilepsy surgery. The presence of such a high concordance between the clinical and morphological data, together with the occurrence of epilepsy and febrile seizures in three generations of the family pedigree points towards a possible genetic nature of the observed FCD type IIIa. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  5. Cortical processes associated with continuous balance control as revealed by EEG spectral power.

    Science.gov (United States)

    Hülsdünker, T; Mierau, A; Neeb, C; Kleinöder, H; Strüder, H K

    2015-04-10

    Balance is a crucial component in numerous every day activities such as locomotion. Previous research has reported distinct changes in cortical theta activity during transient balance instability. However, there remains little understanding of the neural mechanisms underlying continuous balance control. This study aimed to investigate cortical theta activity during varying difficulties of continuous balance tasks, as well as examining the relationship between theta activity and balance performance. 37 subjects completed nine balance tasks with different levels of surface stability and base of support. Throughout the balancing task, electroencephalogram (EEG) was recorded from 32 scalp locations. ICA-based artifact rejection was applied and spectral power was analyzed in the theta frequency band. Theta power increased in the frontal, central, and parietal regions of the cortex when balance tasks became more challenging. In addition, fronto-central and centro-parietal theta power correlated with balance performance. This study demonstrates the involvement of the cerebral cortex in maintaining upright posture during continuous balance tasks. Specifically, the results emphasize the important role of frontal and parietal theta oscillations in balance control. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Biomechanics of far cortical locking.

    Science.gov (United States)

    Bottlang, Michael; Feist, Florian

    2011-02-01

    The development of far cortical locking (FCL) was motivated by a conundrum: locked plating constructs provide inherently rigid stabilization, yet they should facilitate biologic fixation and secondary bone healing that relies on flexible fixation to stimulate callus formation. Recent studies have confirmed that the high stiffness of standard locked plating constructs can suppress interfragmentary motion to a level that is insufficient to reliably promote secondary fracture healing by callus formation. Furthermore, rigid locking screws cause an uneven stress distribution that may lead to stress fracture at the end screw and stress shielding under the plate. This review summarizes four key features of FCL constructs that have been shown to enhance fixation and healing of fractures: flexible fixation, load distribution, progressive stiffening, and parallel interfragmentary motion. Specifically, flexible fixation provided by FCL reduces the stiffness of a locked plating construct by 80% to 88% to actively promote callus proliferation similar to an external fixator. Load is evenly distributed between FCL screws to mitigate stress risers at the end screw. Progressive stiffening occurs by near cortex support of FCL screws and provides additional support under elevated loading. Finally, parallel interfragmentary motion by the S-shaped flexion of FCL screws promotes symmetric callus formation. In combination, these features of FCL constructs have been shown to induce more callus and to yield significantly stronger and more consistent healing compared with standard locked plating constructs. As such, FCL constructs function as true internal fixators by replicating the biomechanical behavior and biologic healing response of external fixators.

  7. Insomnia is Associated with Cortical Hyperarousal as Early as Adolescence.

    Science.gov (United States)

    Fernandez-Mendoza, Julio; Li, Yun; Vgontzas, Alexandros N; Fang, Jidong; Gaines, Jordan; Calhoun, Susan L; Liao, Duanping; Bixler, Edward O

    2016-05-01

    To examine whether insomnia is associated with spectral electroencephalographic (EEG) dynamics in the beta (15-35Hz) range during sleep in an adolescent general population sample. A case-control sample of 44 adolescents from the Penn State Child Cohort underwent a 9-h polysomnography, clinical history and physical examination. We examined low-beta (15-25 Hz) and high-beta (25-35 Hz) relative power at central EEG derivations during sleep onset latency (SOL), sleep onset (SO), non-rapid eye movement (NREM) sleep, and wake after sleep onset (WASO). Compared to controls (n = 21), individuals with insomnia (n = 23) showed increased SOL and WASO and decreased sleep duration and efficiency, while no differences in sleep architecture were found. Insomniacs showed increased low-beta and high-beta relative power during SOL, SO, and NREM sleep as compared to controls. High-beta relative power was greater during all sleep and wake states in insomniacs with short sleep duration as compared to individuals with insomnia with normal sleep duration. Adolescent insomnia is associated with increased beta EEG power during sleep, which suggests that cortical hyperarousal is present in individuals with insomnia as early as adolescence. Interestingly, cortical hyperarousal is greatest in individuals with insomnia with short sleep duration and may explain the sleep complaints of those with normal sleep duration. Disturbed cortical networks may be a shared mechanism putting individuals with insomnia at risk of psychiatric disorders. © 2016 Associated Professional Sleep Societies, LLC.

  8. Commercial incineration demonstration

    International Nuclear Information System (INIS)

    Borduin, L.C.; Neuls, A.S.

    1981-01-01

    Low-level radioactive wastes (LLW) generated by nuclear utilities presently are shipped to commercial burial grounds for disposal. Substantially increasing shipping and disposal charges have sparked renewed industry interest in incineration and other advanced volume reduction techniques as potential cost-saving measures. Repeated inquiries from industry sources regarding LLW applicability of the Los Alamos controlled-air incineration (CAI) design led DOE to initiate this commercial demonstration program in FY-1980. The selected program approach to achieving CAI demonstration at a utility site is a DOE sponsored joint effort involving Los Alamos, a nuclear utility, and a liaison subcontractor. Required development tasks and responsibilities of the particpants are described. Target date for project completion is the end of FY-1985

  9. Cortical oscillatory activity during spatial echoic memory.

    Science.gov (United States)

    Kaiser, Jochen; Walker, Florian; Leiberg, Susanne; Lutzenberger, Werner

    2005-01-01

    In human magnetoencephalogram, we have found gamma-band activity (GBA), a putative measure of cortical network synchronization, during both bottom-up and top-down auditory processing. When sound positions had to be retained in short-term memory for 800 ms, enhanced GBA was detected over posterior parietal cortex, possibly reflecting the activation of higher sensory storage systems along the hypothesized auditory dorsal space processing stream. Additional prefrontal GBA increases suggested an involvement of central executive networks in stimulus maintenance. The present study assessed spatial echoic memory with the same stimuli but a shorter memorization interval of 200 ms. Statistical probability mapping revealed posterior parietal GBA increases at 80 Hz near the end of the memory phase and both gamma and theta enhancements in response to the test stimulus. In contrast to the previous short-term memory study, no prefrontal gamma or theta enhancements were detected. This suggests that spatial echoic memory is performed by networks along the putative auditory dorsal stream, without requiring an involvement of prefrontal executive regions.

  10. Cortical Integration of Audio-Visual Information

    Science.gov (United States)

    Vander Wyk, Brent C.; Ramsay, Gordon J.; Hudac, Caitlin M.; Jones, Warren; Lin, David; Klin, Ami; Lee, Su Mei; Pelphrey, Kevin A.

    2013-01-01

    We investigated the neural basis of audio-visual processing in speech and non-speech stimuli. Physically identical auditory stimuli (speech and sinusoidal tones) and visual stimuli (animated circles and ellipses) were used in this fMRI experiment. Relative to unimodal stimuli, each of the multimodal conjunctions showed increased activation in largely non-overlapping areas. The conjunction of Ellipse and Speech, which most resembles naturalistic audiovisual speech, showed higher activation in the right inferior frontal gyrus, fusiform gyri, left posterior superior temporal sulcus, and lateral occipital cortex. The conjunction of Circle and Tone, an arbitrary audio-visual pairing with no speech association, activated middle temporal gyri and lateral occipital cortex. The conjunction of Circle and Speech showed activation in lateral occipital cortex, and the conjunction of Ellipse and Tone did not show increased activation relative to unimodal stimuli. Further analysis revealed that middle temporal regions, although identified as multimodal only in the Circle-Tone condition, were more strongly active to Ellipse-Speech or Circle-Speech, but regions that were identified as multimodal for Ellipse-Speech were always strongest for Ellipse-Speech. Our results suggest that combinations of auditory and visual stimuli may together be processed by different cortical networks, depending on the extent to which speech or non-speech percepts are evoked. PMID:20709442

  11. Perceptual incongruence influences bistability and cortical activation

    NARCIS (Netherlands)

    Brouwer, G.J.; Tong, F.; Hagoort, P.; van Ee, R.

    2009-01-01

    We employed a parametric psychophysical design in combination with functional imaging to examine the influence of metric changes in perceptual incongruence on perceptual alternation rates and cortical responses. Subjects viewed a bistable stimulus defined by incongruent depth cues; bistability

  12. Cortical electrophysiological network dynamics of feedback learning

    NARCIS (Netherlands)

    Cohen, M.X.; Wilmes, K.A.; van de Vijver, I.

    2011-01-01

    Understanding the neurophysiological mechanisms of learning is important for both fundamental and clinical neuroscience. We present a neurophysiologically inspired framework for understanding cortical mechanisms of feedback-guided learning. This framework is based on dynamic changes in systems-level

  13. Cortical areas involved in Arabic number reading.

    Science.gov (United States)

    Roux, F-E; Lubrano, V; Lauwers-Cances, V; Giussani, C; Démonet, J-F

    2008-01-15

    Distinct functional pathways for processing words and numbers have been hypothesized from the observation of dissociated impairments of these categories in brain-damaged patients. We aimed to identify the cortical areas involved in Arabic number reading process in patients operated on for various brain lesions. Direct cortical electrostimulation was prospectively used in 60 brain mappings. We used object naming and two reading tasks: alphabetic script (sentences and number words) and Arabic number reading. Cortical areas involved in Arabic number reading were identified according to location, type of interference, and distinctness from areas associated with other language tasks. Arabic number reading was sustained by small cortical areas, often extremely well localized (area (Brodmann area 45), the anterior part of the dominant supramarginal gyrus (Brodmann area 40; p area (Brodmann area 37; p areas.

  14. The Diversity of Cortical Inhibitory Synapses

    Directory of Open Access Journals (Sweden)

    Yoshiyuki eKubota

    2016-04-01

    Full Text Available The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their IPSP size is not uniform. Thus cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit.

  15. Probiotics protect mice from ovariectomy-induced cortical bone loss.

    Science.gov (United States)

    Ohlsson, Claes; Engdahl, Cecilia; Fåk, Frida; Andersson, Annica; Windahl, Sara H; Farman, Helen H; Movérare-Skrtic, Sofia; Islander, Ulrika; Sjögren, Klara

    2014-01-01

    The gut microbiota (GM) modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx) results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L) strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix) given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh) treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

  16. Probiotics protect mice from ovariectomy-induced cortical bone loss.

    Directory of Open Access Journals (Sweden)

    Claes Ohlsson

    Full Text Available The gut microbiota (GM modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L strain, L. paracasei DSM13434 (L. para or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

  17. Insomnia is Associated with Cortical Hyperarousal as Early as Adolescence

    Science.gov (United States)

    Fernandez-Mendoza, Julio; Li, Yun; Vgontzas, Alexandros N.; Fang, Jidong; Gaines, Jordan; Calhoun, Susan L.; Liao, Duanping; Bixler, Edward O.

    2016-01-01

    Study Objectives: To examine whether insomnia is associated with spectral electroencephalographic (EEG) dynamics in the beta (15–35Hz) range during sleep in an adolescent general population sample. Methods: A case-control sample of 44 adolescents from the Penn State Child Cohort underwent a 9-h polysomnography, clinical history and physical examination. We examined low-beta (15–25 Hz) and high-beta (25–35 Hz) relative power at central EEG derivations during sleep onset latency (SOL), sleep onset (SO), non-rapid eye movement (NREM) sleep, and wake after sleep onset (WASO). Results: Compared to controls (n = 21), individuals with insomnia (n = 23) showed increased SOL and WASO and decreased sleep duration and efficiency, while no differences in sleep architecture were found. Insomniacs showed increased low-beta and high-beta relative power during SOL, SO, and NREM sleep as compared to controls. High-beta relative power was greater during all sleep and wake states in insomniacs with short sleep duration as compared to individuals with insomnia with normal sleep duration. Conclusions: Adolescent insomnia is associated with increased beta EEG power during sleep, which suggests that cortical hyperarousal is present in individuals with insomnia as early as adolescence. Interestingly, cortical hyperarousal is greatest in individuals with insomnia with short sleep duration and may explain the sleep complaints of those with normal sleep duration. Disturbed cortical networks may be a shared mechanism putting individuals with insomnia at risk of psychiatric disorders. Citation: Fernandez-Mendoza J, Li Y, Vgontzas AN, Fang J, Gaines J, Calhoun SL, Liao D, Bixler EO. Insomnia is associated with cortical hyperarousal as early as adolescence. SLEEP 2016;39(5):1029–1036. PMID:26951400

  18. Determining the cortical target of transcranial magnetic stimulation.

    Science.gov (United States)

    Thielscher, A; Wichmann, F A

    2009-10-01

    Determining the cortical region that is effectively targeted by TMS to induce a reproducible behavioral effect is a non-trivial problem. In mapping experiments, a grid of coil positions is used to systematically assess the TMS effect on, e.g. muscle responses or error rates. The center-of-mass (CoM) of the response distribution is projected onto the cortex to determine the likely target site, implicitly assuming the existence of a single, contiguous target. The mapping results, however, often contain several local maxima. These could either stem from measurement noise, or hint towards a distributed target region. Critically, the calculation of a CoM, by design, treats multiple maxima as if they were noise. Here, a stringent hierarchical sigmoidal model fitting approach is developed that determines the cortical target(s) from TMS mapping based on electric field calculations. Monte-Carlo simulations are used to assess the significance and the goodness-of-fit of the sigmoidal fits, and to obtain confidence regions around the calculated targets. The approach was applied to mapping data on visual suppression (N=7). In all subjects, we reliably identified two or three neighboring targets commonly contributing to the suppression effect (average distance+/-SD: 7.7+/-2.3 mm). This demonstrates that (i) the assumption of a single CoM is not generally valid and (ii) the combination of TMS mapping with the fitting approach has a cortical resolution of TMS.

  19. Motor features in posterior cortical atrophy and their imaging correlates.

    Science.gov (United States)

    Ryan, Natalie S; Shakespeare, Timothy J; Lehmann, Manja; Keihaninejad, Shiva; Nicholas, Jennifer M; Leung, Kelvin K; Fox, Nick C; Crutch, Sebastian J

    2014-12-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Motor features in posterior cortical atrophy and their imaging correlates☆

    Science.gov (United States)

    Ryan, Natalie S.; Shakespeare, Timothy J.; Lehmann, Manja; Keihaninejad, Shiva; Nicholas, Jennifer M.; Leung, Kelvin K.; Fox, Nick C.; Crutch, Sebastian J.

    2014-01-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. PMID:25086839

  1. Dense neuron clustering explains connectivity statistics in cortical microcircuits.

    Directory of Open Access Journals (Sweden)

    Vladimir V Klinshov

    Full Text Available Local cortical circuits appear highly non-random, but the underlying connectivity rule remains elusive. Here, we analyze experimental data observed in layer 5 of rat neocortex and suggest a model for connectivity from which emerge essential observed non-random features of both wiring and weighting. These features include lognormal distributions of synaptic connection strength, anatomical clustering, and strong correlations between clustering and connection strength. Our model predicts that cortical microcircuits contain large groups of densely connected neurons which we call clusters. We show that such a cluster contains about one fifth of all excitatory neurons of a circuit which are very densely connected with stronger than average synapses. We demonstrate that such clustering plays an important role in the network dynamics, namely, it creates bistable neural spiking in small cortical circuits. Furthermore, introducing local clustering in large-scale networks leads to the emergence of various patterns of persistent local activity in an ongoing network activity. Thus, our results may bridge a gap between anatomical structure and persistent activity observed during working memory and other cognitive processes.

  2. Towards a mathematical theory of cortical micro-circuits.

    Directory of Open Access Journals (Sweden)

    Dileep George

    2009-10-01

    Full Text Available The theoretical setting of hierarchical Bayesian inference is gaining acceptance as a framework for understanding cortical computation. In this paper, we describe how Bayesian belief propagation in a spatio-temporal hierarchical model, called Hierarchical Temporal Memory (HTM, can lead to a mathematical model for cortical circuits. An HTM node is abstracted using a coincidence detector and a mixture of Markov chains. Bayesian belief propagation equations for such an HTM node define a set of functional constraints for a neuronal implementation. Anatomical data provide a contrasting set of organizational constraints. The combination of these two constraints suggests a theoretically derived interpretation for many anatomical and physiological features and predicts several others. We describe the pattern recognition capabilities of HTM networks and demonstrate the application of the derived circuits for modeling the subjective contour effect. We also discuss how the theory and the circuit can be extended to explain cortical features that are not explained by the current model and describe testable predictions that can be derived from the model.

  3. Propagation of a dorsal cortical fracture of the third metacarpal bone in two horses

    International Nuclear Information System (INIS)

    Spurlock, G.H.

    1988-01-01

    Seemingly, propagation of a dorsal cortical fracture in the third metacarpal bone developed after continued race performance in 2 horses. Historically, both horses had intermittent lameness that had responded to nonsteroidal anti-inflammatory drugs and brief rest periods. However, lameness in both horses had increased in severity. Radiography revealed a dorsal cortical fracture of the third metacarpal bone, with propagation of the fracture plane proximally. Fractures were incomplete and healed with stall rest in both horses

  4. Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Karunamuni, Roshan [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Bartsch, Hauke; White, Nathan S. [Department of Radiology, University of California San Diego, La Jolla, California (United States); Moiseenko, Vitali; Carmona, Ruben; Marshall, Deborah C.; Seibert, Tyler M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McDonald, Carrie R. [Department of Psychiatry, University of California San Diego, La Jolla, California (United States); Farid, Nikdokht; Krishnan, Anithapriya; Kuperman, Joshua [Department of Radiology, University of California San Diego, La Jolla, California (United States); Mell, Loren [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Brewer, James B.; Dale, Anders M. [Department of Radiology, University of California San Diego, La Jolla, California (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2016-02-01

    Purpose: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thickness between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. Results: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. Conclusions: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT.

  5. Hippocampal neurogenesis and cortical cellular plasticity in Wahlberg's epauletted fruit bat: a qualitative and quantitative study.

    Science.gov (United States)

    Gatome, Catherine W; Mwangi, Deter K; Lipp, Hans-Peter; Amrein, Irmgard

    2010-01-01

    Species-specific characteristics of neuronal plasticity emerging from comparative studies can address the functional relevance of hippocampal or cortical plasticity in the light of ecological adaptation and evolutionary history of a given species. Here, we present a quantitative and qualitative analysis of neurogenesis in young and adult free-living Wahlberg's epauletted fruit bats. Using the markers for proliferating cell nuclear antigen (PCNA), bromodeoxyuridine (BrdU), doublecortin (DCX) and polysialic acid neural cell adhesion molecule (PSA-NCAM), our findings in the hippocampus, olfactory bulb and cortical regions are described and compared to reports in other mammals. Expressed as a percentage of the total number of granule cells, PCNA- and BrdU-positive cells accounted for 0.04 in young to 0.01% in adult animals; DCX-positive cells for 0.05 (young) to 0.01% (adult); PSA-NCAM-positive cells for 0.1 (young) to 0.02% (adult), and pyknotic cells for 0.007 (young) to 0.005% (adult). The numbers were comparable to other long-lived, late-maturing mammals such as primates. A significant increase in the total granule cell number from young to adult animals demonstrated the successful formation and integration of new cells. In adulthood, granule cell number appeared stable and was surprisingly low in comparison to other species. Observations in the olfactory bulb and rostral migratory stream were qualitatively similar to descriptions in other species. In the ventral horn of the lateral ventricle, we noted prominent expression of DCX and PSA-NCAM forming a temporal migratory stream targeting the piriform cortex, possibly reflecting the importance of olfaction to these species. Low, but persistent hippocampal neurogenesis in non-echolocating fruit bats contrasted the findings in echolocating microbats, in which hippocampal neurogenesis was largely absent. Together with the observed intense cortical plasticity in the olfactory system of fruit bats we suggest a

  6. Individual Movement Variability Magnitudes Are Explained by Cortical Neural Variability.

    Science.gov (United States)

    Haar, Shlomi; Donchin, Opher; Dinstein, Ilan

    2017-09-13

    Humans exhibit considerable motor variability even across trivial reaching movements. This variability can be separated into specific kinematic components such as extent and direction that are thought to be governed by distinct neural processes. Here, we report that individual subjects (males and females) exhibit different magnitudes of kinematic variability, which are consistent (within individual) across movements to different targets and regardless of which arm (right or left) was used to perform the movements. Simultaneous fMRI recordings revealed that the same subjects also exhibited different magnitudes of fMRI variability across movements in a variety of motor system areas. These fMRI variability magnitudes were also consistent across movements to different targets when performed with either arm. Cortical fMRI variability in the posterior-parietal cortex of individual subjects explained their movement-extent variability. This relationship was apparent only in posterior-parietal cortex and not in other motor system areas, thereby suggesting that individuals with more variable movement preparation exhibit larger kinematic variability. We therefore propose that neural and kinematic variability are reliable and interrelated individual characteristics that may predispose individual subjects to exhibit distinct motor capabilities. SIGNIFICANCE STATEMENT Neural activity and movement kinematics are remarkably variable. Although intertrial variability is rarely studied, here, we demonstrate that individual human subjects exhibit distinct magnitudes of neural and kinematic variability that are reproducible across movements to different targets and when performing these movements with either arm. Furthermore, when examining the relationship between cortical variability and movement variability, we find that cortical fMRI variability in parietal cortex of individual subjects explained their movement extent variability. This enabled us to explain why some subjects

  7. Cortical recovery of swallowing function in wound botulism

    Directory of Open Access Journals (Sweden)

    Ringelstein Erich B

    2008-05-01

    Full Text Available Abstract Background Botulism is a rare disease caused by intoxication leading to muscle weakness and rapidly progressive dysphagia. With adequate therapy signs of recovery can be observed within several days. In the last few years, brain imaging studies carried out in healthy subjects showed activation of the sensorimotor cortex and the insula during volitional swallowing. However, little is known about cortical changes and compensation mechanisms accompanying swallowing pathology. Methods In this study, we applied whole-head magnetoencephalography (MEG in order to study changes in cortical activation in a 27-year-old patient suffering from wound botulism during recovery from dysphagia. An age-matched group of healthy subjects served as control group. A self-paced swallowing paradigm was performed and data were analyzed using synthetic aperture magnetometry (SAM. Results The first MEG measurement, carried out when the patient still demonstrated severe dysphagia, revealed strongly decreased activation of the somatosensory cortex but a strong activation of the right insula and marked recruitment of the left posterior parietal cortex (PPC. In the second measurement performed five days later after clinical recovery from dysphagia we found a decreased activation in these two areas and a bilateral cortical activation of the primary and secondary sensorimotor cortex comparable to the results seen in a healthy control group. Conclusion These findings indicate parallel development to normalization of swallowing related cortical activation and clinical recovery from dysphagia and highlight the importance of the insula and the PPC for the central coordination of swallowing. The results suggest that MEG examination of swallowing can reflect short-term changes in patients suffering from neurogenic dysphagia.

  8. Commercial incineration demonstration

    International Nuclear Information System (INIS)

    Vavruska, J.S.; Borduin, L.C.

    1982-01-01

    Low-level radioactive wastes (LLW) generated by nuclear utilities presently are shipped to commercial burial grounds for disposal. Increasing transportation and disposal costs have caused industry to consider incineration as a cost-effective means of volume reduction of combustible LLW. Repeated inquiries from the nuclear industry regarding the applicability of the Los Alamos controlled air incineration (CAI) design led the DOE to initiate a commercial demonstration program in FY-1980. Development studies and results in support of this program involving ion exchange resin incineration and fission/activation product distributions within the Los Alamos CAI are described

  9. Role of adult neurogenesis in hippocampal-cortical memory consolidation

    Science.gov (United States)

    2014-01-01

    Acquired memory is initially dependent on the hippocampus (HPC) for permanent memory formation. This hippocampal dependency of memory recall progressively decays with time, a process that is associated with a gradual increase in dependency upon cortical structures. This process is commonly referred to as systems consolidation theory. In this paper, we first review how memory becomes hippocampal dependent to cortical dependent with an emphasis on the interactions that occur between the HPC and cortex during systems consolidation. We also review the mechanisms underlying the gradual decay of HPC dependency during systems consolidation from the perspective of memory erasures by adult hippocampal neurogenesis. Finally, we discuss the relationship between systems consolidation and memory precision. PMID:24552281

  10. Cortical complexity in bipolar disorder applying a spherical harmonics approach.

    Science.gov (United States)

    Nenadic, Igor; Yotter, Rachel A; Dietzek, Maren; Langbein, Kerstin; Sauer, Heinrich; Gaser, Christian

    2017-05-30

    Recent studies using surface-based morphometry of structural magnetic resonance imaging data have suggested that some changes in bipolar disorder (BP) might be neurodevelopmental in origin. We applied a novel analysis of cortical complexity based on fractal dimensions in high-resolution structural MRI scans of 18 bipolar disorder patients and 26 healthy controls. Our region-of-interest based analysis revealed increases in fractal dimensions (in patients relative to controls) in left lateral orbitofrontal cortex and right precuneus, and decreases in right caudal middle frontal, entorhinal cortex, and right pars orbitalis, and left fusiform and posterior cingulate cortices. While our analysis is preliminary, it suggests that early neurodevelopmental pathologies might contribute to bipolar disorder, possibly through genetic mechanisms. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  11. Cortical venous thrombosis following exogenous androgen use for bodybuilding.

    Science.gov (United States)

    Sveinsson, Olafur; Herrman, Lars

    2013-02-05

    There are only a few reports of patients developing cerebral venous sinus thrombosis (CVST) after androgen therapy. We present a young man who developed cortical venous thrombosis after using androgens to increase muscle mass. He was hospitalised for parasthesia and dyspraxia in the left hand followed by a generalised tonic-clonic seizure. At admission, he was drowsy, not fully orientated, had sensory inattention, pronation drift and a positive extensor response, all on the left side. The patient had been using anabolic steroids (dainabol 20 mg/day) for the last month for bodybuilding. CT angiography showed a right cortical venous thrombosis. Anticoagulation therapy was started with intravenous heparin for 11 days and oral anticoagulation (warfarin) thereafter. A control CT angiography 4 months later showed resolution of the thrombosis. He recovered fully.

  12. Development of global cortical networks in early infancy.

    Science.gov (United States)

    Homae, Fumitaka; Watanabe, Hama; Otobe, Takayuki; Nakano, Tamami; Go, Tohshin; Konishi, Yukuo; Taga, Gentaro

    2010-04-07

    Human cognition and behaviors are subserved by global networks of neural mechanisms. Although the organization of the brain is a subject of interest, the process of development of global cortical networks in early infancy has not yet been clarified. In the present study, we explored developmental changes in these networks from several days to 6 months after birth by examining spontaneous fluctuations in brain activity, using multichannel near-infrared spectroscopy. We set up 94 measurement channels over the frontal, temporal, parietal, and occipital regions of the infant brain. The obtained signals showed complex time-series properties, which were characterized as 1/f fluctuations. To reveal the functional connectivity of the cortical networks, we calculated the temporal correlations of continuous signals between all the pairs of measurement channels. We found that the cortical network organization showed regional dependency and dynamic changes in the course of development. In the temporal, parietal, and occipital regions, connectivity increased between homologous regions in the two hemispheres and within hemispheres; in the frontal regions, it decreased progressively. Frontoposterior connectivity changed to a "U-shaped" pattern within 6 months: it decreases from the neonatal period to the age of 3 months and increases from the age of 3 months to the age of 6 months. We applied cluster analyses to the correlation coefficients and showed that the bilateral organization of the networks begins to emerge during the first 3 months of life. Our findings suggest that these developing networks, which form multiple clusters, are precursors of the functional cerebral architecture.

  13. Focal Cortical Thickness Correlates of Exceptional Memory Training in Vedic Priests

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    Giridhar Padmanabhan Kalamangalam

    2014-10-01

    Full Text Available The capacity for semantic memory – the ability to acquire and store knowledge of the world - is highly developed in the human brain. In particular, semantic memory assimilated through an auditory route may be a uniquely human capacity. One method of obtaining neurobiological insight into auditory semantic memory mechanisms is through the study of experts. In this work, we study a group of Hindu Vedic priests, whose religious training requires the memorization of vast tracts of scriptural texts through an oral tradition, recalled spontaneously during a lifetime of subsequent spiritual practice. We demonstrate focal increases of cortical thickness in the dominant prefrontal lobe and non-dominant temporal lobe in Vedic priests, in comparison to a group of matched controls. The findings are relevant to current hypotheses regarding cognitive processes underlying storage and recall of long-term declarative memory.

  14. High frequency deep brain stimulation attenuates subthalamic and cortical rhythms in Parkinson’s disease

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    Diane eWhitmer

    2012-06-01

    Full Text Available Parkinson’s disease (PD is marked by excessive synchronous activity in the beta (8-35 Hz band throughout the cortico-basal ganglia network. The optimal location of high frequency deep brain stimulation (HF DBS within the subthalamic nucleus (STN region and the location of maximal beta hypersynchrony are currently matters of debate. Additionally, the effect of STN HF DBS on neural synchrony in functionally connected regions of motor cortex is unknown and of great interest. Scalp EEG studies demonstrated that stimulation of the STN can activate motor cortex antidromically, but the spatial specificity of this effect has not been examined. The present study examined the effect of STN HF DBS on neural synchrony within the cortico-basal ganglia network in patients with PD. We measured local field potentials dorsal to and within the STN of PD patients, and additionally in the motor cortex in a subset of these patients. We used diffusion tensor imaging (DTI to guide the placement of subdural cortical surface electrodes over the DTI-identified origin of the hyperdirect pathway between motor cortex and the STN. The results demonstrated that local beta power was attenuated during HF DBS both dorsal to and within the STN. The degree of attenuation was monotonic with increased DBS voltages in both locations, but this voltage-dependent effect was greater in the central STN than dorsal to the STN (p < 0.05. Cortical signals over the estimated origin of the hyperdirect pathway also demonstrated attenuation of beta hypersynchrony during DBS dorsal to or within STN, whereas signals from non-specific regions of motor cortex were not attenuated. The spatially specific suppression of beta synchrony in the motor cortex support the hypothesis that DBS may treat Parkinsonism by reducing excessive synchrony in the functionally connected sensorimotor network.

  15. Waste and Disposal: Demonstration

    International Nuclear Information System (INIS)

    Neerdael, B.; Buyens, M.; De Bruyn, D.; Volckaert, G.

    2002-01-01

    Within the Belgian R and D programme on geological disposal, demonstration experiments have become increasingly important. In this contribution to the scientific report 2001, an overview is given of SCK-CEN's activities and achievements in the field of large-scale demonstration experiments. In 2001, main emphasis was on the PRACLAY project, which is a large-scale experiment to demonstrate the construction and the operation of a gallery for the disposal of HLW in a clay formation. The PRACLAY experiment will contribute to enhance understanding of water flow and mass transport in dense clay-based materials as well as to improve the design of the reference disposal concept. In the context of PRACLAY, a surface experiment (OPHELIE) has been developed to prepare and to complement PRACLAY-related experimental work in the HADES Underground Research Laboratory. In 2001, efforts were focussed on the operation of the OPHELIE mock-up. SCK-CEN also contributed to the SELFRAC roject which studies the self-healing of fractures in a clay formation

  16. The developing human connectome project: A minimal processing pipeline for neonatal cortical surface reconstruction.

    Science.gov (United States)

    Makropoulos, Antonios; Robinson, Emma C; Schuh, Andreas; Wright, Robert; Fitzgibbon, Sean; Bozek, Jelena; Counsell, Serena J; Steinweg, Johannes; Vecchiato, Katy; Passerat-Palmbach, Jonathan; Lenz, Gregor; Mortari, Filippo; Tenev, Tencho; Duff, Eugene P; Bastiani, Matteo; Cordero-Grande, Lucilio; Hughes, Emer; Tusor, Nora; Tournier, Jacques-Donald; Hutter, Jana; Price, Anthony N; Teixeira, Rui Pedro A G; Murgasova, Maria; Victor, Suresh; Kelly, Christopher; Rutherford, Mary A; Smith, Stephen M; Edwards, A David; Hajnal, Joseph V; Jenkinson, Mark; Rueckert, Daniel

    2018-06-01

    The Developing Human Connectome Project (dHCP) seeks to create the first 4-dimensional connectome of early life. Understanding this connectome in detail may provide insights into normal as well as abnormal patterns of brain development. Following established best practices adopted by the WU-MINN Human Connectome Project (HCP), and pioneered by FreeSurfer, the project utilises cortical surface-based processing pipelines. In this paper, we propose a fully automated processing pipeline for the structural Magnetic Resonance Imaging (MRI) of the developing neonatal brain. This proposed pipeline consists of a refined framework for cortical and sub-cortical volume segmentation, cortical surface extraction, and cortical surface inflation, which has been specifically designed to address considerable differences between adult and neonatal brains, as imaged using MRI. Using the proposed pipeline our results demonstrate that images collected from 465 subjects ranging from 28 to 45 weeks post-menstrual age (PMA) can be processed fully automatically; generating cortical surface models that are topologically correct, and correspond well with manual evaluations of tissue boundaries in 85% of cases. Results improve on state-of-the-art neonatal tissue segmentation models and significant errors were found in only 2% of cases, where these corresponded to subjects with high motion. Downstream, these surfaces will enhance comparisons of functional and diffusion MRI datasets, supporting the modelling of emerging patterns of brain connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Cortical depth dependent population receptive field attraction by spatial attention in human V1.

    Science.gov (United States)

    Klein, Barrie P; Fracasso, Alessio; van Dijk, Jelle A; Paffen, Chris L E; Te Pas, Susan F; Dumoulin, Serge O

    2018-04-27

    Visual spatial attention concentrates neural resources at the attended location. Recently, we demonstrated that voluntary spatial attention attracts population receptive fields (pRFs) toward its location throughout the visual hierarchy. Theoretically, both a feed forward or feedback mechanism could underlie pRF attraction in a given cortical area. Here, we use sub-millimeter ultra-high field functional MRI to measure pRF attraction across cortical depth and assess the contribution of feed forward and feedback signals to pRF attraction. In line with previous findings, we find consistent attraction of pRFs with voluntary spatial attention in V1. When assessed as a function of cortical depth, we find pRF attraction in every cortical portion (deep, center and superficial), although the attraction is strongest in deep cortical portions (near the gray-white matter boundary). Following the organization of feed forward and feedback processing across V1, we speculate that a mixture of feed forward and feedback processing underlies pRF attraction in V1. Specifically, we propose that feedback processing contributes to the pRF attraction in deep cortical portions. Copyright © 2018. Published by Elsevier Inc.

  18. IGCC technology and demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Palonen, J [A. Ahlstrom Corporation, Karhula (Finland). Hans Ahlstrom Lab.; Lundqvist, R G [A. Ahlstrom Corporation, Helsinki (Finland); Staahl, K [Sydkraft AB, Malmoe (Sweden)

    1997-12-31

    Future energy production will be performed by advanced technologies that are more efficient, more environmentally friendly and less expensive than current technologies. Integrated gasification combined cycle (IGCC) power plants have been proposed as one of these systems. Utilising biofuels in future energy production will also be emphasised since this lowers substantially carbon dioxide emissions into the atmosphere due to the fact that biomass is a renewable form of energy. Combining advanced technology and biomass utilisation is for this reason something that should and will be encouraged. A. Ahlstrom Corporation of Finland and Sydkraft AB of Sweden have as one part of company strategies adopted this approach for the future. The companies have joined their resources in developing a biomass-based IGCC system with the gasification part based on pressurised circulating fluidized-bed technology. With this kind of technology electrical efficiency can be substantially increased compared to conventional power plants. As a first concrete step, a decision has been made to build a demonstration plant. This plant, located in Vaernamo, Sweden, has already been built and is now in commissioning and demonstration stage. The system comprises a fuel drying plant, a pressurised CFB gasifier with gas cooling and cleaning, a gas turbine, a waste heat recovery unit and a steam turbine. The plant is the first in the world where the integration of a pressurised gasifier with a gas turbine will be realised utilising a low calorific gas produced from biomass. The capacity of the Vaernamo plant is 6 MW of electricity and 9 MW of district heating. Technology development is in progress for design of plants of sizes from 20 to 120 MWe. The paper describes the Bioflow IGCC system, the Vaernamo demonstration plant and experiences from the commissioning and demonstration stages. (orig.)

  19. IGCC technology and demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Palonen, J. [A. Ahlstrom Corporation, Karhula (Finland). Hans Ahlstrom Lab.; Lundqvist, R.G. [A. Ahlstrom Corporation, Helsinki (Finland); Staahl, K. [Sydkraft AB, Malmoe (Sweden)

    1996-12-31

    Future energy production will be performed by advanced technologies that are more efficient, more environmentally friendly and less expensive than current technologies. Integrated gasification combined cycle (IGCC) power plants have been proposed as one of these systems. Utilising biofuels in future energy production will also be emphasised since this lowers substantially carbon dioxide emissions into the atmosphere due to the fact that biomass is a renewable form of energy. Combining advanced technology and biomass utilisation is for this reason something that should and will be encouraged. A. Ahlstrom Corporation of Finland and Sydkraft AB of Sweden have as one part of company strategies adopted this approach for the future. The companies have joined their resources in developing a biomass-based IGCC system with the gasification part based on pressurised circulating fluidized-bed technology. With this kind of technology electrical efficiency can be substantially increased compared to conventional power plants. As a first concrete step, a decision has been made to build a demonstration plant. This plant, located in Vaernamo, Sweden, has already been built and is now in commissioning and demonstration stage. The system comprises a fuel drying plant, a pressurised CFB gasifier with gas cooling and cleaning, a gas turbine, a waste heat recovery unit and a steam turbine. The plant is the first in the world where the integration of a pressurised gasifier with a gas turbine will be realised utilising a low calorific gas produced from biomass. The capacity of the Vaernamo plant is 6 MW of electricity and 9 MW of district heating. Technology development is in progress for design of plants of sizes from 20 to 120 MWe. The paper describes the Bioflow IGCC system, the Vaernamo demonstration plant and experiences from the commissioning and demonstration stages. (orig.)

  20. Sulcal set optimization for cortical surface registration.

    Science.gov (United States)

    Joshi, Anand A; Pantazis, Dimitrios; Li, Quanzheng; Damasio, Hanna; Shattuck, David W; Toga, Arthur W; Leahy, Richard M

    2010-04-15

    Flat mapping based cortical surface registration constrained by manually traced sulcal curves has been widely used for inter subject comparisons of neuroanatomical data. Even for an experienced neuroanatomist, manual sulcal tracing can be quite time consuming, with the cost increasing with the number of sulcal curves used for registration. We present a method for estimation of an optimal subset of size N(C) from N possible candidate sulcal curves that minimizes a mean squared error metric over all combinations of N(C) curves. The resulting procedure allows us to estimate a subset with a reduced number of curves to be traced as part of the registration procedure leading to optimal use of manual labeling effort for registration. To minimize the error metric we analyze the correlation structure of the errors in the sulcal curves by modeling them as a multivariate Gaussian distribution. For a given subset of sulci used as constraints in surface registration, the proposed model estimates registration error based on the correlation structure of the sulcal errors. The optimal subset of constraint curves consists of the N(C) sulci that jointly minimize the estimated error variance for the subset of unconstrained curves conditioned on the N(C) constraint curves. The optimal subsets of sulci are presented and the estimated and actual registration errors for these subsets are computed. Copyright 2009 Elsevier Inc. All rights reserved.

  1. Detection and quantification of regional cortical gray matter damage in multiple sclerosis utilizing gradient echo MRI

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    Jie Wen

    2015-01-01

    Full Text Available Cortical gray matter (GM damage is now widely recognized in multiple sclerosis (MS. The standard MRI does not reliably detect cortical GM lesions, although cortical volume loss can be measured. In this study, we demonstrate that the gradient echo MRI can reliably and quantitatively assess cortical GM damage in MS patients using standard clinical scanners. High resolution multi-gradient echo MRI was used for regional mapping of tissue-specific MRI signal transverse relaxation rate values (R2* in 10 each relapsing–remitting, primary-progressive and secondary-progressive MS subjects. A voxel spread function method was used to correct artifacts induced by background field gradients. R2* values from healthy controls (HCs of varying ages were obtained to establish baseline data and calculate ΔR2* values – age-adjusted differences between MS patients and HC. Thickness of cortical regions was also measured in all subjects. In cortical regions, ΔR2* values of MS patients were also adjusted for changes in cortical thickness. Symbol digit modalities (SDMT and paced auditory serial addition (PASAT neurocognitive tests, as well as Expanded Disability Status Score, 25-foot timed walk and nine-hole peg test results were also obtained on all MS subjects. We found that ΔR2* values were lower in multiple cortical GM and normal appearing white matter (NAWM regions in MS compared with HC. ΔR2* values of global cortical GM and several specific cortical regions showed significant (p < 0.05 correlations with SDMT and PASAT scores, and showed better correlations than volumetric measures of the same regions. Neurological tests not focused on cognition (Expanded Disability Status Score, 25-foot timed walk and nine-hole peg tests showed no correlation with cortical GM ΔR2* values. The technique presented here is robust and reproducible. It requires less than 10 min and can be implemented on any MRI scanner. Our results show that quantitative tissue-specific R2

  2. Structural and functional evaluation of cortical motor areas in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Cosottini, Mirco; Pesaresi, Ilaria; Piazza, Selina; Diciotti, Stefano; Cecchi, Paolo; Fabbri, Serena; Carlesi, Cecilia; Mascalchi, Mario; Siciliano, Gabriele

    2012-03-01

    The structural and functional data gathered with Magnetic Resonance Imaging (MRI) techniques about the brain cortical motor damage in Amyotrophic Lateral Sclerosis (ALS) are controversial. In fact some structural MRI studies showed foci of gray matter (GM) atrophy in the precentral gyrus, even in the early stage, while others did not. Most functional MRI (fMRI) studies in ALS reported hyperactivation of extra-primary motor cortices, while contradictory results were obtained on the activation of the primary motor cortex. We aimed to investigate the cortical motor circuitries in ALS patients by a combined structural and functional approach. Twenty patients with definite ALS and 16 healthy subjects underwent a structural examination with acquisition of a 3D T1-weighted sequence and fMRI examination during a maximal force handgrip task executed with the right-hand, the left-hand and with both hands simultaneously. The T1-weighted images were analyzed with Voxel-Based Morphometry (VBM) that showed several clusters of reduced cortical GM in ALS patients compared to controls including the pre and postcentral gyri, the superior, middle and inferior frontal gyri, the supplementary motor area, the superior and inferior parietal cortices and the temporal lobe, bilaterally but more extensive on the right side. In ALS patients a significant hypoactivation of the primary sensory motor cortex and frontal dorsal premotor areas as compared to controls was observed. The hypoactivated areas matched with foci of cortical atrophy demonstrated by VBM. The fMRI analysis also showed an enhanced activation in the ventral premotor frontal areas and in the parietal cortex pertaining to the fronto-parietal motor circuit which paralleled with disease progression rate and matched with cortical regions of atrophy. The hyperactivation of the fronto-parietal circuit was asymmetric and prevalent in the left hemisphere. VBM and fMRI identified structural and functional markers of an extended

  3. Assessment of cortical and sub-cortical function in neonates by electrophysiological monitoring

    NARCIS (Netherlands)

    Jennekens, W.

    2012-01-01

    The aim of this thesis was the assessment of cortical and sub-cortical function in neonates by electrophysiological monitoring, i.e. to evaluate the function of the neonatal cortex and brainstem through quantitative analysis of signals readily available in the NICU. These signals include

  4. Crowdsourcing for error detection in cortical surface delineations.

    Science.gov (United States)

    Ganz, Melanie; Kondermann, Daniel; Andrulis, Jonas; Knudsen, Gitte Moos; Maier-Hein, Lena

    2017-01-01

    With the recent trend toward big data analysis, neuroimaging datasets have grown substantially in the past years. While larger datasets potentially offer important insights for medical research, one major bottleneck is the requirement for resources of medical experts needed to validate automatic processing results. To address this issue, the goal of this paper was to assess whether anonymous nonexperts from an online community can perform quality control of MR-based cortical surface delineations derived by an automatic algorithm. So-called knowledge workers from an online crowdsourcing platform were asked to annotate errors in automatic cortical surface delineations on 100 central, coronal slices of MR images. On average, annotations for 100 images were obtained in less than an hour. When using expert annotations as reference, the crowd on average achieves a sensitivity of 82 % and a precision of 42 %. Merging multiple annotations per image significantly improves the sensitivity of the crowd (up to 95 %), but leads to a decrease in precision (as low as 22 %). Our experiments show that the detection of errors in automatic cortical surface delineations generated by anonymous untrained workers is feasible. Future work will focus on increasing the sensitivity of our method further, such that the error detection tasks can be handled exclusively by the crowd and expert resources can be focused on error correction.

  5. The characteristics of cortical glucose metabolism in amblyopia

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Ji Young [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of); Lee, Dong Soo; Chung, June Key; Shin, Seung Ai; Lee, Myung Chul [College of Medicine, Ewha Womans Univ., Seoul (Korea, Republic of)

    2000-07-01

    Cortical metabolism of amblyopia patients was investigated with F-18-FDG PET and Statistical Parametric Mapping (SPM) and quantificiation based on volume of interest (VOI) by statistical probabilistic anatomical map (SPAM). In 9 amblyopic patients (12{+-}7 years ) and 20 normal subjects (23{+-}2 years), F-18-FDG PET scans were peformed in amblyopic patients after amblyopic eye or sound eye was patch-closed during PET studies. SPM was done with SPM96. By multiplying SPAM to FDG images, counts of 98 VOI's were calculated and compared with 3 S. D. range of those of normal subjects. On SPM, cortical metabolism decreased (p<0.05) in occipital lobe (Ba 17, 18, 19), superior partietal lobe (Ba 7), and inferior temporal lobe (BA 37, 20). FDG uptake of gyri of occuipital lobe was decreased in 2 and increased in 2, and was normal in the other 5. FDG uptake of gyri of parietal, frontal, and temporal lobes were decreased in FDG uptake on these VOIs. We conclude that cortical metabolism in occipital lobe and extraoccipital lobes was variable but was consistent regardless of visual input during PET studies in amblyopic patients. SPM and quantification of functional images using SPAM could reveal subtle differences or changes according to visual input. The significance of metabolic changes of extraoccipital lobes should be studies further.

  6. The characteristics of cortical glucose metabolism in amblyopia

    International Nuclear Information System (INIS)

    Ahn, Ji Young; Lee, Dong Soo; Chung, June Key; Shin, Seung Ai; Lee, Myung Chul

    2000-01-01

    Cortical metabolism of amblyopia patients was investigated with F-18-FDG PET and Statistical Parametric Mapping (SPM) and quantificiation based on volume of interest (VOI) by statistical probabilistic anatomical map (SPAM). In 9 amblyopic patients (12±7 years ) and 20 normal subjects (23±2 years), F-18-FDG PET scans were peformed in amblyopic patients after amblyopic eye or sound eye was patch-closed during PET studies. SPM was done with SPM96. By multiplying SPAM to FDG images, counts of 98 VOI's were calculated and compared with 3 S. D. range of those of normal subjects. On SPM, cortical metabolism decreased (p<0.05) in occipital lobe (Ba 17, 18, 19), superior partietal lobe (Ba 7), and inferior temporal lobe (BA 37, 20). FDG uptake of gyri of occuipital lobe was decreased in 2 and increased in 2, and was normal in the other 5. FDG uptake of gyri of parietal, frontal, and temporal lobes were decreased in FDG uptake on these VOIs. We conclude that cortical metabolism in occipital lobe and extraoccipital lobes was variable but was consistent regardless of visual input during PET studies in amblyopic patients. SPM and quantification of functional images using SPAM could reveal subtle differences or changes according to visual input. The significance of metabolic changes of extraoccipital lobes should be studies further

  7. Mouse embryonic retina delivers information controlling cortical neurogenesis.

    Directory of Open Access Journals (Sweden)

    Ciro Bonetti

    2010-12-01

    Full Text Available The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded, the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal. Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system.

  8. Visual-induced expectations modulate auditory cortical responses

    Directory of Open Access Journals (Sweden)

    Virginie evan Wassenhove

    2015-02-01

    Full Text Available Active sensing has important consequences on multisensory processing (Schroeder et al. 2010. Here, we asked whether in the absence of saccades, the position of the eyes and the timing of transient colour changes of visual stimuli could selectively affect the excitability of auditory cortex by predicting the where and the when of a sound, respectively. Human participants were recorded with magnetoencephalography (MEG while maintaining the position of their eyes on the left, right, or centre of the screen. Participants counted colour changes of the fixation cross while neglecting sounds which could be presented to the left, right or both ears. First, clear alpha power increases were observed in auditory cortices, consistent with participants’ attention directed to visual inputs. Second, colour changes elicited robust modulations of auditory cortex responses (when prediction seen as ramping activity, early alpha phase-locked responses, and enhanced high-gamma band responses in the contralateral side of sound presentation. Third, no modulations of auditory evoked or oscillatory activity were found to be specific to eye position. Altogether, our results suggest that visual transience can automatically elicit a prediction of when a sound will occur by changing the excitability of auditory cortices irrespective of the attended modality, eye position or spatial congruency of auditory and visual events. To the contrary, auditory cortical responses were not significantly affected by eye position suggesting that where predictions may require active sensing or saccadic reset to modulate auditory cortex responses, notably in the absence of spatial orientation to sounds.

  9. Cortical modulation of short-latency TMS-evoked potentials

    Directory of Open Access Journals (Sweden)

    Domenica eVeniero

    2013-01-01

    Full Text Available Transcranial magnetic stimulation - electroencephalogram (TMS-EEG co-registration offers the opportunity to test reactivity of brain areas across distinct conditions through TMS-evoked potentials (TEPs. Several TEPs have been described, their functional meaning being largely unknown. In particular, short-latency potentials peaking at 5 (P5 and 8 (N8 ms after the TMS pulse have been recently described, but because of their huge amplitude, the problem of whether their origin is cortical or not has been opened. To gain information about these components, we employed a protocol that modulates primary motor cortex excitability (MI through an exclusively cortical phenomena: low frequency stimulation of premotor area (PMC. TMS was applied simultaneously with EEG recording from 70 electrodes. Amplitude of TEPs evoked by 200 single-pulses TMS delivered over MI at 110% of resting motor threshold was measured before and after applying 900 TMS conditioning stimuli to left premotor cortex with 1 Hz repetition rate. Single subject analyses showed reduction in TEPs amplitude after PMC conditioning in a sample of participants and increase in TEPs amplitude in two subjects. No effects were found on corticospinal excitability as recorded by motor evoked potentials (MEPs. Furthermore, correlation analysis showed an inverse relation between the effects of the conditioning protocol on P5-N8 complex amplitude and MEPs amplitude. Because the effects of the used protocol have been ascribed to a cortical interaction between premotor area and MI, we suggest that despite the sign of P5-N8 amplitude modulation is not consistent across participant, this modulation could indicate, at least in part, their cortical origin. We conclude that with an accurate experimental procedure early-latency components can be used to evaluate the reactivity of the stimulated cortex.

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

    Directory of Open Access Journals (Sweden)

    Ryo Tamaki

    2017-01-01

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

  11. Somatosensory cortices are required for the acquisition of morphine-induced conditioned place preference.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Meng

    Full Text Available BACKGROUND: Sensory system information is thought to play an important role in drug addiction related responses. However, how somatic sensory information participates in the drug related behaviors is still unclear. Many studies demonstrated that drug addiction represents a pathological usurpation of neural mechanisms of learning and memory that normally relate to the pursuit of rewards. Thus, elucidate the role of somatic sensory in drug related learning and memory is of particular importance to understand the neurobiological mechanisms of drug addiction. PRINCIPAL FINDINGS: In the present study, we investigated the role of somatosensory system in reward-related associative learning using the conditioned place preference model. Lesions were made in somatosensory cortices either before or after conditioning training. We found that lesion of somatosensory cortices before, rather than after morphine conditioning impaired the acquisition of place preference. CONCLUSION: These results demonstrate that somatosensory cortices are necessary for the acquisition but not retention of morphine induced place preference.

  12. Neuroglobin overexpression inhibits oxygen-glucose deprivation-induced mitochondrial permeability transition pore opening in primary cultured mouse cortical neurons.

    Science.gov (United States)

    Yu, Zhanyang; Liu, Ning; Li, Yadan; Xu, Jianfeng; Wang, Xiaoying

    2013-08-01

    Neuroglobin (Ngb) is an endogenous neuroprotective molecule against hypoxic/ischemic brain injury, but the underlying mechanisms remain largely undefined. Our recent study revealed that Ngb can bind to voltage-dependent anion channel (VDAC), a regulator of mitochondria permeability transition (MPT). In this study we examined the role of Ngb in MPT pore (mPTP) opening following oxygen-glucose deprivation (OGD) in primary cultured mouse cortical neurons. Co-immunoprecipitation (Co-IP) and immunocytochemistry showed that the binding between Ngb and VDAC was increased after OGD compared to normoxia, indicating the OGD-enhanced Ngb-VDAC interaction. Ngb overexpression protected primary mouse cortical neurons from OGD-induced neuronal death, to an extent comparable to mPTP opening inhibitor, cyclosporine A (CsA) pretreatment. We further measured the role of Ngb in OGD-induced mPTP opening using Ngb overexpression and knockdown approaches in primary cultured neurons, and recombinant Ngb exposure to isolated mitochondria. Same as CsA pretreatment, Ngb overexpression significantly reduced OGD-induced mPTP opening markers including mitochondria swelling, mitochondrial NAD(+) release, and cytochrome c (Cyt c) release in primary cultured neurons. Recombinant Ngb incubation significantly reduced OGD-induced NAD(+) release and Cyt c release from isolated mitochondria. In contrast, Ngb knockdown significantly increased OGD-induced neuron death, and increased OGD-induced mitochondrial NAD(+) release and Cyt c release as well, and these outcomes could be rescued by CsA pretreatment. In summary, our results demonstrated that Ngb overexpression can inhibit OGD-induced mPTP opening in primary cultured mouse cortical neurons, which may be one of the molecular mechanisms of Ngb's neuroprotection. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Cortical activities of single-trial P300 amplitudes modulated by memory load using simultaneous EEG-fMRI

    Science.gov (United States)

    Zhang, Qiushi; Zhao, Xiaojie; Zhu, Chaozhe; Yang, Xueqian; Yao, Li

    2015-03-01

    The functional magnetic resonance imaging (fMRI) researches on working memory have found that activation of cortical areas appeared dependent on memory load, and event-related potentials (ERP) studies have demonstrated that amplitudes of P300 decreased significantly when working memory load increased. However, the cortical activities related with P300 amplitudes under different memory loads remains unclear. Joint fMRI and EEG analysis which fusions the time and spatial information in simultaneous EEG-fMRI recording can reveal the regional activation at each ERP time point. In this paper, we first used wavelet transform to obtain the single-trial amplitudes of P300 caused by a digital N-back task in the simultaneous EEG-fMRI recording as the ERP feature sequences. Then the feature sequences in 1-back condition and 3-back condition were introduced into general linear model (GLM) separately as parametric modulations to compare the cortical activation under different memory loads. The results showed that the average amplitudes of P300 in 3-back significantly decreased than that in 1-back, and the activities induced by ERP feature sequences in 3-back also significantly decreased than that in the 1-back, including the insular, anterior cingulate cortex, right inferior frontal gyrus, and medial frontal gyrus, which were relevant to the storage, monitoring, and manipulation of information in working memory task. Moreover, the difference in the activation caused by ERP feature showed a positive correlation with the difference in behavioral performance. These findings demonstrated the locations of P300 amplitudes differences modulated by the memory load and its relationship with the behavioral performance.

  14. Alterations in Cortical Sensorimotor Connectivity following Complete Cervical Spinal Cord Injury: A Prospective Resting-State fMRI Study.

    Directory of Open Access Journals (Sweden)

    Akinwunmi Oni-Orisan

    Full Text Available Functional magnetic resonance imaging (fMRI studies have demonstrated alterations during task-induced brain activation in spinal cord injury (SCI patients. The interruption to structural integrity of the spinal cord and the resultant disrupted flow of bidirectional communication between the brain and the spinal cord might contribute to the observed dynamic reorganization (neural plasticity. However, the effect of SCI on brain resting-state connectivity patterns remains unclear. We undertook a prospective resting-state fMRI (rs-fMRI study to explore changes to cortical activation patterns following SCI. With institutional review board approval, rs-fMRI data was obtained in eleven patients with complete cervical SCI (>2 years post injury and nine age-matched controls. The data was processed using the Analysis of Functional Neuroimages software. Region of interest (ROI based analysis was performed to study changes in the sensorimotor network using pre- and post-central gyri as seed regions. Two-sampled t-test was carried out to check for significant differences between the two groups. SCI patients showed decreased functional connectivity in motor and sensory cortical regions when compared to controls. The decrease was noted in ipsilateral, contralateral, and interhemispheric regions for left and right precentral ROIs. Additionally, the left postcentral ROI demonstrated increased connectivity with the thalamus bilaterally in SCI patients. Our results suggest that cortical activation patterns in the sensorimotor network undergo dynamic reorganization following SCI. The presence of these changes in chronic spinal cord injury patients is suggestive of the inherent neural plasticity within the central nervous system.

  15. Electrophysiological Data and the Biophysical Modelling of Local Cortical Circuits

    Directory of Open Access Journals (Sweden)

    Dimitris Pinotsis

    2014-03-01

    empirical MEG data and looked for potential determinants of the spectral properties of an individual's gamma response, and how they relate to underlying visual cortex microcircuitry and excitation/inhibition balance. We found correlations between peak gamma frequency and cortical inhibition (parameterized by the excitatory drive to inhibitory cell populations over subjects. This constitutes a compelling illustration of how non-invasive data can provide quantitative estimates of the spatial properties of neural sources and explain systematic variations in the dynamics those sources generate. Furthermore, the conclusions fitted comfortably with studies of contextual interactions and orientation discrimination suggesting that local contextual interactions in V1 are weaker in individuals with a large V1 area [13, 14]. Finally, we will use dynamic causal modeling and neural fields to test specific hypotheses about precision and gain control based on predictive coding formulations of neuronal processing. We exploited finely sampled electrophysiological responses from awake-behaving monkeys and an experimental manipulation (the contrast of visual stimuli to look at changes in the gain and balance of excitatory and inhibitory influences. Our results suggest that increasing contrast effectively increases the sensitivity or gain of superficial pyramidal cells to inputs from spiny stellate populations. Furthermore, they are consistent with intriguing results showing that the receptive fields of V1 units shrinks with increasing visual contrast. The approach we will illustrate in this paper rests on neural field models that are optimized in relation to observed gamma responses from the visual cortex and are – crucially – compared in terms of their evidence. This provides a principled way to address questions about cortical structure, function and the architectures that underlie neuronal computations.

  16. Cocaine- and amphetamine-regulated transcript facilitates the neurite outgrowth in cortical neurons after oxygen and glucose deprivation through PTN-dependent pathway.

    Science.gov (United States)

    Wang, Y; Qiu, B; Liu, J; Zhu, Wei-Guo; Zhu, S

    2014-09-26

    Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide that plays neuroprotective roles in cerebral ischemia and reperfusion (I/R) injury in animal models or oxygen and glucose deprivation (OGD) in cultured neurons. Recent data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain. However, little is known about the effects of post-treatment with CART during the neuronal recovery after OGD and reoxygenation in cultured primary cortical neurons. The present study was to investigate the role of CART treated after OGD injury in neurons. Primary mouse cortical neurons were subjected to OGD and then treated with CART. Our data show that post-treatment with CART reduced the neuronal apoptosis caused by OGD injury. In addition, CART repaired OGD-impaired cortical neurons by increasing the expression of growth-associated protein 43 (GAP43), which promotes neurite outgrowth. This effect depends on pleiotrophin (PTN) as siRNA-mediated PTN knockdown totally abolished the increase in CART-stimulated GAP43 protein levels. In summary, our findings demonstrate that CART repairs the neuronal injury after OGD by facilitating neurite outgrowth through PTN-dependent pathway. The role for CART in neurite outgrowth makes it a new potential therapeutic agent for the treatment of neurodegenerative diseases. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Low serum vitamin D is associated with higher cortical porosity in elderly men.

    Science.gov (United States)

    Sundh, D; Mellström, D; Ljunggren, Ö; Karlsson, M K; Ohlsson, C; Nilsson, M; Nilsson, A G; Lorentzon, M

    2016-11-01

    Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported. To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men. A population-based cohort of 444 elderly men (mean ± SD age 80.2 ± 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay. Mean cortical porosity at the distal tibia was 14.7% higher (12.5 ± 4.3% vs. 10.9 ± 4.1%, P vitamin D levels compared to the highest. In men with vitamin D deficiency (6.8 pmol L -1 )], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized β = -0.110, R 2 = 1.1%, P = 0.024), area (β = 0.123, R 2 = 1.4%, P = 0.007) and cortical volumetric BMD (β = 0.125, R 2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (β = 0.102, R 2 = 0.9%, P = 0.04). Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry. © 2016 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

  18. Prospective detection of cortical dysplasia on clinical MRI in pediatric intractable epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Radhakrishnan, Rupa; Leach, James L.; Gelfand, Michael J. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Mangano, Francesco T. [Cincinnati Children' s Hospital Medical Center, Department of Neurosurgery, Cincinnati, OH (United States); Rozhkov, Leonid; Greiner, Hansel M. [Cincinnati Children' s Hospital Medical Center, Department of Neurology, Comprehensive Epilepsy Treatment Center, Cincinnati, OH (United States); Miles, Lili [Cincinnati Children' s Hospital Medical Center, Department of Pathology, Cincinnati, OH (United States)

    2016-09-15

    Cortical dysplasia is the most common cause of pediatric refractory epilepsy. MRI detection of epileptogenic lesion is associated with good postsurgical outcome. Additional electrophysiological information is suggested to be helpful in localization of cortical dysplasia. Educational measures were taken to increase the awareness of cortical dysplasia at our institution in the context of a recent International League Against Epilepsy (ILAE 2011) classification of cortical dysplasia. To determine changes in the rate of prospective identification of cortical dysplasia on an initial radiology report and also evaluate the benefit of MRI review as part of a multidisciplinary epilepsy conference in identifying previously overlooked MRI findings. We retrospectively evaluated surgically treated children with refractory epilepsy from 2007 to 2014 with cortical dysplasia on histopathology. We analyzed the initial radiology report, preoperative MRI interpretation at multidisciplinary epilepsy conference and subsequent retrospective MRI review with knowledge of the resection site. We recorded additional electrophysiological data and the presence of lobar concordance with the MRI findings. Of 78 children (44 MRI lesional) evaluated, 18 had initially overlooked MRI findings. Comparing 2007-2010 to 2011-2014, there was improvement in the rate of overlooked findings on the initial radiology report (54% vs. 13% of lesional cases, respectively; P = 0.008). The majority (72%) were identified at a multidisciplinary conference with lobar concordance of findings with at least one additional electrophysiological investigation in 89%. Awareness of current classification schemes of cortical dysplasia and image review in the context of a multidisciplinary conference can lead to improved MRI detection of cortical dysplasia in children. (orig.)

  19. Prospective detection of cortical dysplasia on clinical MRI in pediatric intractable epilepsy

    International Nuclear Information System (INIS)

    Radhakrishnan, Rupa; Leach, James L.; Gelfand, Michael J.; Mangano, Francesco T.; Rozhkov, Leonid; Greiner, Hansel M.; Miles, Lili

    2016-01-01

    Cortical dysplasia is the most common cause of pediatric refractory epilepsy. MRI detection of epileptogenic lesion is associated with good postsurgical outcome. Additional electrophysiological information is suggested to be helpful in localization of cortical dysplasia. Educational measures were taken to increase the awareness of cortical dysplasia at our institution in the context of a recent International League Against Epilepsy (ILAE 2011) classification of cortical dysplasia. To determine changes in the rate of prospective identification of cortical dysplasia on an initial radiology report and also evaluate the benefit of MRI review as part of a multidisciplinary epilepsy conference in identifying previously overlooked MRI findings. We retrospectively evaluated surgically treated children with refractory epilepsy from 2007 to 2014 with cortical dysplasia on histopathology. We analyzed the initial radiology report, preoperative MRI interpretation at multidisciplinary epilepsy conference and subsequent retrospective MRI review with knowledge of the resection site. We recorded additional electrophysiological data and the presence of lobar concordance with the MRI findings. Of 78 children (44 MRI lesional) evaluated, 18 had initially overlooked MRI findings. Comparing 2007-2010 to 2011-2014, there was improvement in the rate of overlooked findings on the initial radiology report (54% vs. 13% of lesional cases, respectively; P = 0.008). The majority (72%) were identified at a multidisciplinary conference with lobar concordance of findings with at least one additional electrophysiological investigation in 89%. Awareness of current classification schemes of cortical dysplasia and image review in the context of a multidisciplinary conference can lead to improved MRI detection of cortical dysplasia in children. (orig.)

  20. In Vivo Assessment of Elasticity of Child Rib Cortical Bone Using Quantitative Computed Tomography

    Directory of Open Access Journals (Sweden)

    Y. Zhu

    2017-01-01

    Full Text Available Elasticity of the child rib cortical bone is poorly known due to the difficulties in obtaining specimens to perform conventional tests. It was shown on the femoral cortical bone that elasticity is strongly correlated with density for both children and adults through a unique relationship. Thus, it is assumed that the relationships between the elasticity and density of adult rib cortical bones could be expanded to include that of children. This study estimated in vivo the elasticity of the child rib cortical bone using quantitative computed tomography (QCT. Twenty-eight children (from 1 to 18 y.o. were considered. Calibrated QCT images were prescribed for various thoracic pathologies. The Hounsfield units were converted to bone mineral density (BMD. A relationship between the BMD and the elasticity of the rib cortical bone was applied to estimate the elasticity of children’s ribs in vivo. The estimated elasticity increases with growth (7.1 ± 2.5 GPa at 1 y.o. up to 11.6 ± 1.9 GPa at 18 y.o.. This data is in agreement with the few previous values obtained using direct measurements. This methodology paves the way for in vivo assessment of the elasticity of the child cortical bone based on calibrated QCT images.

  1. Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

    Science.gov (United States)

    Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

    2017-07-04

    This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

  2. Quantifying indices of short- and long-range white matter connectivity at each cortical vertex.

    Directory of Open Access Journals (Sweden)

    Maria Carmela Padula

    Full Text Available Several neurodevelopmental diseases are characterized by impairments in cortical morphology along with altered white matter connectivity. However, the relationship between these two measures is not yet clear. In this study, we propose a novel methodology to compute and display metrics of white matter connectivity at each cortical point. After co-registering the extremities of the tractography streamlines with the cortical surface, we computed two measures of connectivity at each cortical vertex: the mean tracts' length, and the proportion of short- and long-range connections. The proposed measures were tested in a clinical sample of 62 patients with 22q11.2 deletion syndrome (22q11DS and 57 typically developing individuals. Using these novel measures, we achieved a fine-grained visualization of the white matter connectivity patterns at each vertex of the cortical surface. We observed an intriguing pattern of both increased and decreased short- and long-range connectivity in 22q11DS, that provides novel information about the nature and topology of white matter alterations in the syndrome. We argue that the method presented in this study opens avenues for additional analyses of the relationship between cortical properties and patterns of underlying structural connectivity, which will help clarifying the intrinsic mechanisms that lead to altered brain structure in neurodevelopmental disorders.

  3. Towards an optimal paradigm for simultaneously recording cortical and brainstem auditory evoked potentials.

    Science.gov (United States)

    Bidelman, Gavin M

    2015-02-15

    Simultaneous recording of brainstem and cortical event-related brain potentials (ERPs) may offer a valuable tool for understanding the early neural transcription of behaviorally relevant sounds and the hierarchy of signal processing operating at multiple levels of the auditory system. To date, dual recordings have been challenged by technological and physiological limitations including different optimal parameters necessary to elicit each class of ERP (e.g., differential adaptation/habitation effects and number of trials to obtain adequate response signal-to-noise ratio). We investigated a new stimulus paradigm for concurrent recording of the auditory brainstem frequency-following response (FFR) and cortical ERPs. The paradigm is "optimal" in that it uses a clustered stimulus presentation and variable interstimulus interval (ISI) to (i) achieve the most ideal acquisition parameters for eliciting subcortical and cortical responses, (ii) obtain an adequate number of trials to detect each class of response, and (iii) minimize neural adaptation/habituation effects. Comparison between clustered and traditional (fixed, slow ISI) stimulus paradigms revealed minimal change in amplitude or latencies of either the brainstem FFR or cortical ERP. The clustered paradigm offered over a 3× increase in recording efficiency compared to conventional (fixed ISI presentation) and thus, a more rapid protocol for obtaining dual brainstem-cortical recordings in individual listeners. We infer that faster recording of subcortical and cortical potentials might allow more complete and sensitive testing of neurophysiological function and aid in the differential assessment of auditory function. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Paradiaphyseal calcific tendinitis with cortical bone erosion.

    Science.gov (United States)

    Fritz, P; Bardin, T; Laredo, J D; Ziza, J M; D'Anglejan, G; Lansaman, J; Bucki, B; Forest, M; Kuntz, D

    1994-05-01

    To determine the clinical, radiologic, and histologic features of calcific tendinitis with cortical bone erosion. The records of 6 patients with paradiaphyseal calcific tendinitis and adjacent bone cortex erosion were reviewed. Calcific tendinitis involved the linea aspera in 4 patients, the bicipital groove in 1 patient, and the deltoid insertion in another. Calcium deposits were associated with cortical bone erosions, revealed on plain radiographs in 4 patients and computed tomography scans in 2. Bone scans were performed in 2 patients and showed local hyperfixation of the isotope. In 4 patients, suspicion of a neoplasm led to a biopsy. Calcium deposits appeared to be surrounded by a foreign body reaction with numerous giant cells. Apatite crystals were identified by transmission electron microscopy and elemental analysis in 1 surgical sample. Paradiaphyseal calcific tendinitis with cortical bone erosion is an uncommon presentation of apatite deposition disease.

  5. Reduced cortical thickness in gambling disorder

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Chamberlain, Samuel R

    2015-01-01

    with significant reductions (average 15.8-19.9 %) in cortical thickness, versus controls, predominantly in right frontal cortical regions. Pronounced right frontal morphometric brain abnormalities occur in gambling disorder, supporting neurobiological overlap with substance disorders and its recent......Gambling disorder has recently been recognized as a prototype 'behavioral addiction' by virtue of its inclusion in the DSM-5 category of 'Substance-Related and Addictive Disorders.' Despite its newly acquired status and prevalence rate of 1-3 % globally, relatively little is known regarding...... the neurobiology of this disorder. The aim of this study was to explore cortical morphometry in untreated gambling disorder, for the first time. Subjects with gambling disorder (N = 16) free from current psychotropic medication or psychiatric comorbidities, and healthy controls (N = 17), were entered...

  6. Scaling of motor cortical excitability during unimanual force generation.

    Science.gov (United States)

    Perez, Monica A; Cohen, Leonardo G

    2009-10-01

    During performance of a unimanual force generation task primary motor cortices (M1s) experience clear functional changes. Here, we evaluated the way in which M1s interact during parametric increases in right wrist flexion force in healthy volunteers. We measured the amplitude and the slope of motor evoked potentials (MEP) recruitment curves to transcranial magnetic stimulation (TMS) in the left and right flexor carpi radialis (FCR) muscles at rest and during 10%, 30% and 70% of maximal wrist flexion force. At rest, no differences were observed in the amplitude and slope of MEP recruitment curves in the left and right FCR muscles. With increasing right wrist flexion force, MEP amplitudes increased in both FCR muscles, with larger amplitudes in the right FCR. We found a significant correlation between the left and right MEP amplitudes across conditions. The slope of right and left FCR MEP recruitment curve was significantly steeper at 70% of force compared to rest and 10% of force. A significant correlation between the slope of left and right FCR MEP amplitudes was found at 70% of force only. Our results indicate a differential scaling of excitability in the corticospinal system controlling right and left FCR muscles at increasing levels of unimanual force generation. Specifically, these data highlights that at strong levels of unimanual force the increases in motor cortical excitability with increasing TMS stimulus intensities follow a similar pattern in both M1s, while at low levels of force they do not.

  7. Rasmussen's encephalitis presenting as focal cortical dysplasia

    Directory of Open Access Journals (Sweden)

    D.J. O'Rourke

    2014-01-01

    Full Text Available Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD and discuss the literature on this topic.

  8. Rasmussen's encephalitis presenting as focal cortical dysplasia

    Science.gov (United States)

    O'Rourke, D.J.; Bergin, A.; Rotenberg, A.; Peters, J.; Gorman, M.; Poduri, A.; Cryan, J.; Lidov, H.; Madsen, J.; Harini, C.

    2014-01-01

    Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD) and discuss the literature on this topic. PMID:25667877

  9. Cortical Networks for Visual Self-Recognition

    Science.gov (United States)

    Sugiura, Motoaki

    This paper briefly reviews recent developments regarding the brain mechanisms of visual self-recognition. A special cognitive mechanism for visual self-recognition has been postulated based on behavioral and neuropsychological evidence, but its neural substrate remains controversial. Recent functional imaging studies suggest that multiple cortical mechanisms play self-specific roles during visual self-recognition, reconciling the existing controversy. Respective roles for the left occipitotemporal, right parietal, and frontal cortices in symbolic, visuospatial, and conceptual aspects of self-representation have been proposed.

  10. Cortical networks for visual self-recognition

    International Nuclear Information System (INIS)

    Sugiura, Motoaki

    2007-01-01

    This paper briefly reviews recent developments regarding the brain mechanisms of visual self-recognition. A special cognitive mechanism for visual self-recognition has been postulated based on behavioral and neuropsychological evidence, but its neural substrate remains controversial. Recent functional imaging studies suggest that multiple cortical mechanisms play self-specific roles during visual self-recognition, reconciling the existing controversy. Respective roles for the left occipitotemporal, right parietal, and frontal cortices in symbolic, visuospatial, and conceptual aspects of self-representation have been proposed. (author)

  11. Effects of high-fat diet and losartan on renal cortical blood flow using contrast ultrasound imaging.

    Science.gov (United States)

    Declèves, Anne-Emilie; Rychak, Joshua J; Smith, Dan J; Sharma, Kumar

    2013-11-01

    Obesity-related kidney disease occurs as a result of complex interactions between metabolic and hemodynamic effects. Changes in microvascular perfusion may play a major role in kidney disease; however, these changes are difficult to assess in vivo. Here, we used perfusion ultrasound imaging to evaluate cortical blood flow in a mouse model of high-fat diet-induced kidney disease. C57BL/6J mice were randomized to a standard diet (STD) or a high-fat diet (HFD) for 30 wk and then treated either with losartan or a placebo for an additional 6 wk. Noninvasive ultrasound perfusion imaging of the kidney was performed during infusion of a microbubble contrast agent. Blood flow within the microvasculature of the renal cortex and medulla was derived from imaging data. An increase in the time required to achieve full cortical perfusion was observed for HFD mice relative to STD. This was reversed following treatment with losartan. These data were concurrent with an increased glomerular filtration rate in HFD mice compared with STD- or HFD-losartan-treated mice. Losartan treatment also abrogated fibro-inflammatory disease, assessed by markers at the protein and messenger level. Finally, a reduction in capillary density was found in HFD mice, and this was reversed upon losartan treatment. This suggests that alterations in vascular density may be responsible for the elevated perfusion time observed by imaging. These data demonstrate that ultrasound contrast imaging is a robust and sensitive method for evaluating changes in renal microvascular perfusion and that cortical perfusion time may be a useful parameter for evaluating obesity-related renal disease.

  12. Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat cortical neurons via inhibition of oxidative stress, excitatory amino acids release and P53/Bax.

    Science.gov (United States)

    He, Zhi; Hu, Min; Zha, Yun-hong; Li, Zi-cheng; Zhao, Bo; Yu, Ling-ling; Yu, Min; Qian, Ying

    2014-05-01

    Our previous work has demonstrated that piracetam inhibited the decrease in amino acid content induced by chronic hypoperfusion, ameliorated the dysfunction of learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX protein, facilitated the synaptic plasticity, and may be helpful in the treatment of vascular dementia. To explore the precise mechanism, the present study further evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced neuronal damage in rat primary cortical cells. The addition of piracetam to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and lactate dehydrogenase release experiments. Piracetam also lowered the levels of malondialdehyde, nitrogen monoxidum, and xanthine oxidase which was increased in the OGD cells, and enhanced the activities of superoxide dismutase and glutathione peroxidase, which were decreased in the OGD cells. We also demonstrated that piracetam could decrease glutamate and aspartate release when cortical cells were subjected to OGD. Furthermore, Western blot study demonstrated that piracetam attenuated the increased expression of P53 and BAX protein in OGD cells. These observations demonstrated that piracetam reduced OGD-induced neuronal damage by inhibiting the oxidative stress and decreasing excitatory amino acids release and lowering P53/Bax protein expression in OGD cells.

  13. Remodeling sensory cortical maps implants specific behavioral memory.

    Science.gov (United States)

    Bieszczad, K M; Miasnikov, A A; Weinberger, N M

    2013-08-29

    Neural mechanisms underlying the capacity of memory to be rich in sensory detail are largely unknown. A candidate mechanism is learning-induced plasticity that remodels the adult sensory cortex. Here, expansion in the primary auditory cortical (A1) tonotopic map of rats was induced by pairing a 3.66-kHz tone with activation of the nucleus basalis, mimicking the effects of natural associative learning. Remodeling of A1 produced de novo specific behavioral memory, but neither memory nor plasticity was consistently at the frequency of the paired tone, which typically decreased in A1 representation. Rather, there was a specific match between individual subjects' area of expansion and the tone that was strongest in each animal's memory, as determined by post-training frequency generalization gradients. These findings provide the first demonstration of a match between the artificial induction of specific neural representational plasticity and artificial induction of behavioral memory. As such, together with prior and present findings for detection, correlation and mimicry of plasticity with the acquisition of memory, they satisfy a key criterion for neural substrates of memory. This demonstrates that directly remodeling sensory cortical maps is sufficient for the specificity of memory formation. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. The Role of Neuromodulators in Cortical Plasticity. A Computational Perspective

    Science.gov (United States)

    Pedrosa, Victor; Clopath, Claudia

    2017-01-01

    Neuromodulators play a ubiquitous role across the brain in regulating plasticity. With recent advances in experimental techniques, it is possible to study the effects of diverse neuromodulatory states in specific brain regions. Neuromodulators are thought to impact plasticity predominantly through two mechanisms: the gating of plasticity and the upregulation of neuronal activity. However, the consequences of these mechanisms are poorly understood and there is a need for both experimental and theoretical exploration. Here we illustrate how neuromodulatory state affects cortical plasticity through these two mechanisms. First, we explore the ability of neuromodulators to gate plasticity by reshaping the learning window for spike-timing-dependent plasticity. Using a simple computational model, we implement four different learning rules and demonstrate their effects on receptive field plasticity. We then compare the neuromodulatory effects of upregulating learning rate versus the effects of upregulating neuronal activity. We find that these seemingly similar mechanisms do not yield the same outcome: upregulating neuronal activity can lead to either a broadening or a sharpening of receptive field tuning, whereas upregulating learning rate only intensifies the sharpening of receptive field tuning. This simple model demonstrates the need for further exploration of the rich landscape of neuromodulator-mediated plasticity. Future experiments, coupled with biologically detailed computational models, will elucidate the diversity of mechanisms by which neuromodulatory state regulates cortical plasticity. PMID:28119596

  15. REMODELING SENSORY CORTICAL MAPS IMPLANTS SPECIFIC BEHAVIORAL MEMORY

    Science.gov (United States)

    Bieszczad, Kasia M.; Miasnikov, Alexandre A.; Weinberger, Norman M.

    2013-01-01

    Neural mechanisms underlying the capacity of memory to be rich with sensory detail are largely unknown. A candidate mechanism is learning-induced plasticity that remodels adult sensory cortex. Here, expansion in the primary auditory cortical (A1) tonotopic map of rats was induced by pairing a 3.66 kHz tone with activation of the nucleus basalis, mimicking the effects of natural associative learning. Remodeling of A1 produced de novo specific behavioral memory, but neither memory nor plasticity were consistently at the frequency of the paired tone, which typically decreased in A1 representation. Rather, there was a specific match between individual subjects’ area of expansion and the tone that was strongest in each animal’s memory, as determined by post-training frequency generalization gradients. These findings provide the first demonstration of a match between the artificial induction of specific neural representational plasticity and artificial induction of behavioral memory. As such, together with prior and present findings for detection, correlation and mimicry of plasticity with the acquisition of memory, they satisfy a key criterion for neural substrates of memory. This demonstrates that directly remodeling sensory cortical maps is sufficient for the specificity of memory formation. PMID:23639876

  16. Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism

    Energy Technology Data Exchange (ETDEWEB)

    Finkelstein, J.S.; Klibanski, A.; Neer, R.M.; Doppelt, S.H.; Rosenthal, D.I.; Segre, G.V.; Crowley, W.F. Jr. (Massachusetts General Hospital, Boston (USA))

    1989-10-01

    To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), while trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature.

  17. Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism

    International Nuclear Information System (INIS)

    Finkelstein, J.S.; Klibanski, A.; Neer, R.M.; Doppelt, S.H.; Rosenthal, D.I.; Segre, G.V.; Crowley, W.F. Jr.

    1989-01-01

    To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), while trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature

  18. Modeling a space-variant cortical representation for apparent motion.

    Science.gov (United States)

    Wurbs, Jeremy; Mingolla, Ennio; Yazdanbakhsh, Arash

    2013-08-06

    Receptive field sizes of neurons in early primate visual areas increase with eccentricity, as does temporal processing speed. The fovea is evidently specialized for slow, fine movements while the periphery is suited for fast, coarse movements. In either the fovea or periphery discrete flashes can produce motion percepts. Grossberg and Rudd (1989) used traveling Gaussian activity profiles to model long-range apparent motion percepts. We propose a neural model constrained by physiological data to explain how signals from retinal ganglion cells to V1 affect the perception of motion as a function of eccentricity. Our model incorporates cortical magnification, receptive field overlap and scatter, and spatial and temporal response characteristics of retinal ganglion cells for cortical processing of motion. Consistent with the finding of Baker and Braddick (1985), in our model the maximum flash distance that is perceived as an apparent motion (Dmax) increases linearly as a function of eccentricity. Baker and Braddick (1985) made qualitative predictions about the functional significance of both stimulus and visual system parameters that constrain motion perception, such as an increase in the range of detectable motions as a function of eccentricity and the likely role of higher visual processes in determining Dmax. We generate corresponding quantitative predictions for those functional dependencies for individual aspects of motion processing. Simulation results indicate that the early visual pathway can explain the qualitative linear increase of Dmax data without reliance on extrastriate areas, but that those higher visual areas may serve as a modulatory influence on the exact Dmax increase.

  19. Biodiesel Mass Transit Demonstration

    Science.gov (United States)

    2010-04-01

    The Biodiesel Mass Transit Demonstration report is intended for mass transit decision makers and fleet managers considering biodiesel use. This is the final report for the demonstration project implemented by the National Biodiesel Board under a gran...

  20. Authoring Effective Demonstrations

    National Research Council Canada - National Science Library

    Fu, Dan; Jensen, Randy; Salas, Eduardo; Rosen, Michael A; Ramachandran, Sowmya; Upshaw, Christin L; Hinkelman, Elizabeth; Lampton, Don

    2007-01-01

    ... or human role-players for each training event. We report our ongoing efforts to (1) research the nature and purpose of demonstration, articulating guidelines for effective demonstration within a training context, and (2...

  1. Comparing Demonstratives in Kwa

    African Journals Online (AJOL)

    This paper is a comparative study of demonstrative forms in three K wa languages, ... relative distance from the deictic centre, such as English this and that, here and there. ... Mostly, the referents of demonstratives are 'activated' or at least.

  2. Polarized Light Corridor Demonstrations.

    Science.gov (United States)

    Davies, G. R.

    1990-01-01

    Eleven demonstrations of light polarization are presented. Each includes a brief description of the apparatus and the effect demonstrated. Illustrated are strain patterns, reflection, scattering, the Faraday Effect, interference, double refraction, the polarizing microscope, and optical activity. (CW)

  3. Fuel Cell Demonstration Program

    Energy Technology Data Exchange (ETDEWEB)

    Gerald Brun

    2006-09-15

    In an effort to promote clean energy projects and aid in the commercialization of new fuel cell technologies the Long Island Power Authority (LIPA) initiated a Fuel Cell Demonstration Program in 1999 with six month deployments of Proton Exchange Membrane (PEM) non-commercial Beta model systems at partnering sites throughout Long Island. These projects facilitated significant developments in the technology, providing operating experience that allowed the manufacturer to produce fuel cells that were half the size of the Beta units and suitable for outdoor installations. In 2001, LIPA embarked on a large-scale effort to identify and develop measures that could improve the reliability and performance of future fuel cell technologies for electric utility applications and the concept to establish a fuel cell farm (Farm) of 75 units was developed. By the end of October of 2001, 75 Lorax 2.0 fuel cells had been installed at the West Babylon substation on Long Island, making it the first fuel cell demonstration of its kind and size anywhere in the world at the time. Designed to help LIPA study the feasibility of using fuel cells to operate in parallel with LIPA's electric grid system, the Farm operated 120 fuel cells over its lifetime of over 3 years including 3 generations of Plug Power fuel cells (Lorax 2.0, Lorax 3.0, Lorax 4.5). Of these 120 fuel cells, 20 Lorax 3.0 units operated under this Award from June 2002 to September 2004. In parallel with the operation of the Farm, LIPA recruited government and commercial/industrial customers to demonstrate fuel cells as on-site distributed generation. From December 2002 to February 2005, 17 fuel cells were tested and monitored at various customer sites throughout Long Island. The 37 fuel cells operated under this Award produced a total of 712,635 kWh. As fuel cell technology became more mature, performance improvements included a 1% increase in system efficiency. Including equipment, design, fuel, maintenance

  4. Cortical thickness, surface area, and folding alterations in male youths with conduct disorder and varying levels of callous–unemotional traits

    Directory of Open Access Journals (Sweden)

    Graeme Fairchild

    2015-01-01

    Conclusions: Cortical thinning in the superior temporal gyrus may contribute to the social cognitive impairments displayed by youths with CD, whereas reduced OFC SA may lead to impairments in emotion regulation and reward processing in youths with CD. The increased cortical folding observed in the insula may reflect a maturational delay in this region and could mediate the link between CU traits and empathy deficits. Altered cortical folding was observed in childhood-onset and adolescence-onset forms of CD.

  5. Locally formed dopamine inhibits Na+-K+-ATPase activity in rat renal cortical tubule cells

    International Nuclear Information System (INIS)

    Seri, I.; Kone, B.C.; Gullans, S.R.; Aperia, A.; Brenner, B.M.; Ballermann, B.J.

    1988-01-01

    Dopamine, generated locally from L-dopa, inhibits Na + -K + -ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na + -K + -ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate (Qo 2 ) and 86 Rb uptake in renal cortical tubule cell suspensions. L-Dopa did not affect ouabain-insensitive Qo 2 or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive Qo 2 in a concentration-dependent manner, with half-maximal inhibition (K 0.5 ) of 5 x 10 -7 M and a maximal inhibition of 14.1 ± 1.5% at 10 -4 M. L-Dopa also blunted the nystatin-stimulated Qo 2 in a concentration-dependent manner, indicating the L-dopa directly inhibits Na + -K + -ATPase activity and not sodium entry. Ouabain-sensitive 86 Rb uptake was also inhibited by L-dopa. Carbidopa, an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive Qo 2 and 86 Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased. By studying the effect of L-dopa on ouabain-sensitive Qo 2 at increasing extracellular sodium concentrations in the presence of nystatin, the authors demonstrated that the inhibitory effect of locally formed dopamine on the Na + -K + -ATPase is indeed dependent on the sodium available for the enzyme and occurs in an uncompetitive manner

  6. Cortical Silent