TMS-Induced Cortical Potentiation during Wakefulness Locally Increases Slow Wave Activity during Sleep

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: These results provide direct evidence for a link between plastic changes and the local regulation of sleep need

Analysis of the Temporal Organization of Sleep Spindles in the Human Sleep EEG Using a Phenomenological Modeling Approach

The sleep electroencephalogram (EEG) is characterized by typical oscillatory patterns such as sleep spindles and slow waves. Recently, we proposed a method to detect and analyze these patterns using linear autoregressive models for short (≈ 1 s) data segments. We analyzed the temporal organization of sleep spindles and discuss to what extent the observed interevent intervals correspond to properties of stationary stochastic processes and whether additional slow processes, such as slow oscillations, have to be assumed. We have found evidence for such an additional slow process, most pronounced in sleep stage 2

Comparison of different methods for DNA-free RNA isolation from SK-N-MC neuroblastoma

<p>Abstract</p> <p>Background</p> <p>RNA quality and quantity are important factors for ensuring the accuracy of gene expression analysis and other RNA-based downstream applications. Extraction of high quality nucleic acids is difficult from neuronal cells and brain tissues as they are particularly rich in lipids. In addition, most common RNA extraction methods are phenol-based, resulting in RNA that may be incompatible with downstream applications such as gene expression.</p> <p>Findings</p> <p>In this work, a comparative analysis of the RNA quality obtained from SK-N-MC cells was performed using six commonly used RNA isolation kits: two phenol-based kits and four non-phenol based kits. The non-phenol based kits tested AxyPrep Multisource Total RNA Miniprep, RNeasy^®Mini, EasySpin and Ilustra RNAspin Mini RNA Isolation, all performed well and resulted in the isolation of high quality RNA, as evaluated by A₂₆₀/A₂₈₀. The RNA extracted with AxyPrep Multisource Total RNA Miniprep, RNeasy^®Mini and EasySpin provided the highest RNA yields. In particular, the RNA isolated by AxyPrep Multisource Total RNA Miniprep Kit did not show any detectable genomic DNA contamination even without previous DNase treatment or after RNA direct PCR amplification using universal 18S primers.</p> <p>Conclusions</p> <p>The RNA extracted from SK-N-MC cells with AxyPrep Multisource Total RNA Miniprep Kit was superior with respect to the RNA quality and concentration. This kit does not use aggressive organic solvents and RNA free of genomic DNA was isolated without the need for DNase treatment.</p

Surfactant protein D modulates HIV infection of both T-cells and dendritic cells

Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo

Cortical Plasticity Induced by Transcranial Magnetic Stimulation during Wakefulness Affects Electroencephalogram Activity during Sleep

BACKGROUND:Sleep electroencephalogram (EEG) brain oscillations in the low-frequency range show local signs of homeostatic regulation after learning. Such increases and decreases of slow wave activity are limited to the cortical regions involved in specific task performance during wakefulness. Here, we test the hypothesis that reorganization of motor cortex produced by long-term potentiation (LTP) affects EEG activity of this brain area during subsequent sleep. METHODOLOGY/PRINCIPAL FINDINGS:By pairing median nerve stimulation with transcranial magnetic stimulation over the contralateral motor cortex, one can potentiate the motor output, which is presumed to reflect plasticity of the neural circuitry. This paired associative stimulation increases M1 cortical excitability at interstimulus intervals of 25 ms. We compared the scalp distribution of sleep EEG power following paired associative stimulation at 25 ms to that following a control paradigm with 50 ms intervals. It is shown that the experimental manipulation by paired associative stimulation at 25 ms induces a 48% increase in amplitude of motor evoked potentials. This LTP-like potentiation, induced during waking, affects delta and theta EEG power in both REM and non-REM sleep, measured during the following night. Slow-wave activity increases in some frontal and prefrontal derivations and decreases at sites neighboring and contralateral to the stimulated motor cortex. The magnitude of increased amplitudes of motor evoked potentials by the paired associative stimulation at 25 ms predicts enhancements of slow-wave activity in prefrontal regions. CONCLUSIONS/SIGNIFICANCE:An LTP-like paradigm, presumably inducing increased synaptic strength, leads to changes in local sleep regulation, as indexed by EEG slow-wave activity. Enhancement and depression of slow-wave activity are interpreted in terms of a simultaneous activation of both excitatory and inhibitory circuits consequent to the paired associative stimulation at 25 ms

Integrated Information in Discrete Dynamical Systems: Motivation and Theoretical Framework

This paper introduces a time- and state-dependent measure of integrated information, φ, which captures the repertoire of causal states available to a system as a whole. Specifically, φ quantifies how much information is generated (uncertainty is reduced) when a system enters a particular state through causal interactions among its elements, above and beyond the information generated independently by its parts. Such mathematical characterization is motivated by the observation that integrated information captures two key phenomenological properties of consciousness: (i) there is a large repertoire of conscious experiences so that, when one particular experience occurs, it generates a large amount of information by ruling out all the others; and (ii) this information is integrated, in that each experience appears as a whole that cannot be decomposed into independent parts. This paper extends previous work on stationary systems and applies integrated information to discrete networks as a function of their dynamics and causal architecture. An analysis of basic examples indicates the following: (i) φ varies depending on the state entered by a network, being higher if active and inactive elements are balanced and lower if the network is inactive or hyperactive. (ii) φ varies for systems with identical or similar surface dynamics depending on the underlying causal architecture, being low for systems that merely copy or replay activity states. (iii) φ varies as a function of network architecture. High φ values can be obtained by architectures that conjoin functional specialization with functional integration. Strictly modular and homogeneous systems cannot generate high φ because the former lack integration, whereas the latter lack information. Feedforward and lattice architectures are capable of generating high φ but are inefficient. (iv) In Hopfield networks, φ is low for attractor states and neutral states, but increases if the networks are optimized to achieve tension between local and global interactions. These basic examples appear to match well against neurobiological evidence concerning the neural substrates of consciousness. More generally, φ appears to be a useful metric to characterize the capacity of any physical system to integrate information

Morning and Evening-Type Differences in Slow Waves during NREM Sleep Reveal Both Trait and State-Dependent Phenotypes

Brain recovery after prolonged wakefulness is characterized by increased density, amplitude and slope of slow waves (SW, <4 Hz) during non-rapid eye movement (NREM) sleep. These SW comprise a negative phase, during which cortical neurons are mostly silent, and a positive phase, in which most neurons fire intensively. Previous work showed, using EEG spectral analysis as an index of cortical synchrony, that Morning-types (M-types) present faster dynamics of sleep pressure than Evening-types (E-types). We thus hypothesized that single SW properties will also show larger changes in M-types than in E-types in response to increased sleep pressure. SW density (number per minute) and characteristics (amplitude, slope between negative and positive peaks, frequency and duration of negative and positive phases) were compared between chronotypes for a baseline sleep episode (BL) and for recovery sleep (REC) after two nights of sleep fragmentation. While SW density did not differ between chronotypes, M-types showed higher SW amplitude and steeper slope than E-types, especially during REC. SW properties were also averaged for 3 NREM sleep periods selected for their decreasing level of sleep pressure (first cycle of REC [REC1], first cycle of BL [BL1] and fourth cycle of BL [BL4]). Slope was significantly steeper in M-types than in E-types in REC1 and BL1. SW frequency was consistently higher and duration of positive and negative phases constantly shorter in M-types than in E-types. Our data reveal that specific properties of cortical synchrony during sleep differ between M-types and E-types, although chronotypes show a similar capacity to generate SW. These differences may involve 1) stable trait characteristics independent of sleep pressure (i.e., frequency and durations) likely linked to the length of silent and burst-firing phases of individual neurons, and 2) specific responses to increased sleep pressure (i.e., slope and amplitude) expected to depend on the synchrony between neurons

Large-Scale Cortical Dynamics of Sleep Slow Waves

Slow waves constitute the main signature of sleep in the electroencephalogram (EEG). They reflect alternating periods of neuronal hyperpolarization and depolarization in cortical networks. While recent findings have demonstrated their functional role in shaping and strengthening neuronal networks, a large-scale characterization of these two processes remains elusive in the human brain. In this study, by using simultaneous scalp EEG and intracranial recordings in 10 epileptic subjects, we examined the dynamics of hyperpolarization and depolarization waves over a large extent of the human cortex. We report that both hyperpolarization and depolarization processes can occur with two different characteristic time durations which are consistent across all subjects. For both hyperpolarization and depolarization waves, their average speed over the cortex was estimated to be approximately 1 m/s. Finally, we characterized their propagation pathways by studying the preferential trajectories between most involved intracranial contacts. For both waves, although single events could begin in almost all investigated sites across the entire cortex, we found that the majority of the preferential starting locations were located in frontal regions of the brain while they had a tendency to end in posterior and temporal regions

Exosomes Derived from M. Bovis BCG Infected Macrophages Activate Antigen-Specific CD4+ and CD8+ T Cells In Vitro and In Vivo

Activation of both CD4+ and CD8+ T cells is required for an effective immune response to an M. tuberculosis infection. However, infected macrophages are poor antigen presenting cells and may be spatially separated from recruited T cells, thus limiting antigen presentation within a granuloma. Our previous studies showed that infected macrophages release from cells small membrane-bound vesicles called exosomes which contain mycobacterial lipid components and showed that these exosomes could stimulate a pro-inflammatory response in naïve macrophages. In the present study we demonstrate that exosomes stimulate both CD4+ and CD8+ splenic T cells isolated from mycobacteria-sensitized mice. Although the exosomes contain MHC I and II as well as costimulatory molecules, maximum stimulation of T cells required prior incubation of exosomes with antigen presenting cells. Exosomes isolated from M. bovis and M. tuberculosis infected macrophages also stimulated activation and maturation of mouse bone marrow-derived dendritic cells. Interestingly, intranasal administration of mice with exosomes isolated from M. bovis BCG infected macrophages induce the generation of memory CD4+ and CD8+ T cells. The isolated T cells also produced IFN-γ upon restimulation with BCG antigens. The release of exosomes from infected macrophages may overcome some of the defects in antigen presentation associated with mycobacterial infections and we suggest that exosomes may be a promising M. tuberculosis vaccine candidate

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns