Comb filters for the removal of transcranial current stimulation artifacts from single channel EEG recordings

Abstract The combination of transcranial alternating current stimulation (tACS) and electroencephalogram (EEG) for mobile and home-based interventions offers the potential for control and adaptation of stimulation parameters. Yet, during stimulation, the EEG is heavily affected by stimulation artifacts. Spatial filters are often unsuited because too few channels are recorded and hardware capabilities are limited. Due to their speed and as they can be used for single channels, we explore the performance of single-channel weighted comb filters on artifact removal. At any given time point t, the recording r(t) is a superposition of a neurophysiological signal n(t), the stimulation artifact a(t) and noise e(t). Now, we can estimate the artifact a(t) based on the recording from an earlier (or later) time-point shifted by the artifacts period. A weighted estimate based on multiple time points has the potential to improve the signal recovery. Therefore, we explored several approaches and evaluated their performance on simulated and real data. The comb kernel filters were implemented in Matlab (https://github.com/agricolab/ARtACS) and Python (https://github.com/agricolab/pyARtACS), and the code is open access under an X11-license. We found that independent of the weighting function, all comb filters exhibit similarity in their suppression of the DC component, the artifacts frequency, and its harmonics. Yet, different weighting functions exhibit different pass-band performance, evident as ringing and amplification, and their induction of time-domain echoes. Interestingly, we note that a causal uniform filter is comparable to more complex approaches, while offering the option for real-time filtering. Comb filters are able to remove tACS artifacts even if only a single channel is available. As comb filters require no assumptions about the shape of the artifact, they might also be useful for filtering of non-sinusoidal, e.g. pulsed or saw-tooth, transcranial current stimulation.

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THU0070 DEFINING SYNOVIAL SIGNATURES IN THE RAT CIA MODEL: WHAT CAN WE LEARN ABOUT RA PROGRESSION?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3695 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 247.2-248

Author(s):

D. Ruelas ◽

R. LI ◽

C. Franci ◽

V. Lira ◽

D. Lopez ◽

...

Keyword(s):

Disease Progression ◽

Synovial Tissue ◽

Current Knowledge ◽

Severe Disease ◽

Unmet Need ◽

Poor Response ◽

Multiple Time ◽

Combination Therapies ◽

Course Of Disease ◽

Time Point

Background:Patients showing inadequate or no response to current therapies represent a key unmet need in rheumatoid arthritis (RA). To address this, novel or combination therapies are of high clinical interest. Identification of novel therapeutic targets requires a greater understanding of the pathogenic molecular drivers in the RA synovium. However, our current knowledge of human molecular patterns that emerge as a result of disease progression is complicated by patient-to-patient heterogeneity and access to synovial tissue.Objectives:Here we use the current knowledge of human synovial heterogeneity to conduct a longitudinal study of global molecular responses in the rat collagen-induced arthritis (CIA) model to better understand synovial biology, improve the preclinical modeling of human disease, and discover novel targets for RA.Methods:A rat CIA model was performed as previously described.1RNA-Seq was performed on 56 knee synovial tissues collected at multiple time points throughout the course of disease. Differential gene expression was determined at each individual time point and longitudinally with disease progression. Published human synovial datasets were used to categorize these genes into myeloid, lymphoid, fibroid, and low inflammatory signatures.2Differentially expressed genes (DEGs) at each time point were compared to human synovial datasets of RA patients before and after treatment. In addition, we compared disease-driven genes in CIA to genes in RA patients that are unchanged following therapy to identify possible combination therapies.Results:Disease pathology in the rat CIA natural history study progressed as expected: significant decreases were seen in body weight, as well as increases in ankle diameter, paw weight, and histopathology scores of joints in collagen-injected vs noninjected rats. There were 1900 DEGs identified between diseased and naïve rats over the course of disease, representing disease-induced gene signatures (Fig. 1). Comparing these DEGs to reported human RA synovial signatures, both the lymphoid and myeloid signatures were found to be highly upregulated. Interestingly, there were no significant DEGs representing the human fibroid and low inflammatory synovial signatures identified in the CIA rat model. This suggests that the rat CIA model most closely models RA patients with an immune synovial phenotype. In addition, we examined the overlap between disease-driven genes in CIA and genes in RA patients that are unchanged following therapy to identify signaling pathways that may be of utility in combination therapy. Of genes that were upregulated in CIA, 94% of genes that mapped to extracellular matrix-receptor pathways remained unchanged in the synovial tissue of RA patients following tocilizumab treatment.Conclusion:Previous studies have shown that nearly 30% of treatment-naïve early RA patients exhibit a strong fibroid phenotype that correlates with less severe disease and a relatively poor response to disease-modifying anti-rheumatic drugs.3These data indicate that the synovial biology associated with such patients (fibroid or pauci-immune) is not well captured in CIA, the most common preclinical RA model. To assess potential new therapies targeting these patients, it will be necessary to develop alternative animal models with more intact fibroid signatures. In addition to these findings, we also characterized the global molecular changes that occur with disease progression in the CIA rat and made a comparison to RA patients on treatment, providing an overall understanding of disease-relevant pathways in the synovium that may point to possible combination therapies.References:[1]Trentham DE, et al.J Exp Med. 1977;146(3):857-868.[2]Dennis G Jr, et al.Arthritis Res Ther. 2014;16(2):R90.[3]Humby F, et al.Ann Rheum Dis. 2019;78(6):761-772.Disclosure of Interests:Debbie Ruelas Employee of: Gilead, Ruidong Li Employee of: Gilead, Christian Franci Employee of: Gilead, Victor Lira Employee of: Gilead, David Lopez Employee of: Gilead, Li Li Employee of: Gilead, Gundula Min-Oo Employee of: Gilead, Julie A. Di Paolo Employee of: Gilead

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cAMP-dependent regulation of IKs single-channel kinetics

The Journal of General Physiology ◽

10.1085/jgp.201611734 ◽

2017 ◽

Vol 149 (8) ◽

pp. 781-798 ◽

Cited By ~ 10

Author(s):

Emely Thompson ◽

Jodene Eldstrom ◽

Maartje Westhoff ◽

Donald McAfee ◽

Elise Balse ◽

...

Keyword(s):

Action Potential ◽

Single Channel ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Surface Expression ◽

Voltage Sensor ◽

Single Channels ◽

Adrenergic Stimulation ◽

Channel Opening ◽

Sensor Activation

The delayed potassium rectifier current, IKs, is composed of KCNQ1 and KCNE1 subunits and plays an important role in cardiac action potential repolarization. During β-adrenergic stimulation, 3′-5′-cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) phosphorylates KCNQ1, producing an increase in IKs current and a shortening of the action potential. Here, using cell-attached macropatches and single-channel recordings, we investigate the microscopic mechanisms underlying the cAMP-dependent increase in IKs current. A membrane-permeable cAMP analog, 8-(4-chlorophenylthio)-cAMP (8-CPT-cAMP), causes a marked leftward shift of the conductance–voltage relation in macropatches, with or without an increase in current size. Single channels exhibit fewer silent sweeps, reduced first latency to opening (control, 1.61 ± 0.13 s; cAMP, 1.06 ± 0.11 s), and increased higher-subconductance-level occupancy in the presence of cAMP. The E160R/R237E and S209F KCNQ1 mutants, which show fixed and enhanced voltage sensor activation, respectively, largely abolish the effect of cAMP. The phosphomimetic KCNQ1 mutations, S27D and S27D/S92D, are much less and not at all responsive, respectively, to the effects of PKA phosphorylation (first latency of S27D + KCNE1 channels: control, 1.81 ± 0.1 s; 8-CPT-cAMP, 1.44 ± 0.1 s, P < 0.05; latency of S27D/S92D + KCNE1: control, 1.62 ± 0.1 s; cAMP, 1.43 ± 0.1 s, nonsignificant). Using total internal reflection fluorescence microscopy, we find no overall increase in surface expression of the channel during exposure to 8-CPT-cAMP. Our data suggest that the cAMP-dependent increase in IKs current is caused by an increase in the likelihood of channel opening, combined with faster openings and greater occupancy of higher subconductance levels, and is mediated by enhanced voltage sensor activation.

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Caffeine-induced inhibition of inositol(1,4,5)-trisphosphate-gated calcium channels from cerebellum.

Molecular Biology of the Cell ◽

10.1091/mbc.5.1.97 ◽

1994 ◽

Vol 5 (1) ◽

pp. 97-103 ◽

Cited By ~ 57

Author(s):

I Bezprozvanny ◽

S Bezprozvannaya ◽

B E Ehrlich

Keyword(s):

Lipid Bilayers ◽

Inhibitory Action ◽

Single Channel ◽

Ryanodine Receptors ◽

Single Channels ◽

Ca Channels ◽

Open Time ◽

Inositol 1,4,5 Trisphosphate ◽

Insp3 Receptors ◽

Intracellular Ca

Effects of the xanthine drug caffeine on inositol (1,4,5)-trisphosphate (InsP3)-gated calcium (Ca) channels from canine cerebellum were studied using single channels incorporated into planar lipid bilayers. Caffeine, used widely as an agonist of ryanodine receptors, inhibited the activity of InsP3-gated Ca channels in a noncooperative fashion with half-inhibition at 1.64 mM caffeine. The frequency of channel openings was decreased more than threefold after addition of 5 mM caffeine; there was only a small effect on mean open time of the channels, and the single channel conductance was unchanged. Increased InsP3 concentration overcame the inhibitory action of caffeine, but caffeine did not reduce specific [3H]InsP3 binding to the receptor. The inhibitory action of caffeine on InsP3 receptors suggests that the action of caffeine on the intracellular Ca pool must be interpreted with caution when both ryanodine receptors and InsP3 receptors are present in the cell.

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Effects of Strontium on the Permeation and Gating Phenotype of Calcium Channels in Hair Cells

Journal of Neurophysiology ◽

10.1152/jn.90473.2008 ◽

2008 ◽

Vol 100 (4) ◽

pp. 2115-2124 ◽

Cited By ~ 4

Author(s):

Adrian Rodriguez-Contreras ◽

Ping Lv ◽

Jun Zhu ◽

Hyo Jeong Kim ◽

Ebenezer N. Yamoah

Keyword(s):

Hair Cell ◽

Single Channel ◽

Single Channels ◽

Physiological Concentration ◽

Closed State ◽

Dependent Inactivation ◽

Intracellular Ca ◽

High Concentrations ◽

Latency Distributions ◽

Channel Properties

To minimize the effects of Ca2+ buffering and signaling, this study sought to examine single Ca2+ channel properties using Sr2+ ions, which substitute well for Ca2+ but bind weakly to intracellular Ca2+ buffers. Two single-channel fluctuations were distinguished by their sensitivity to dihydropyridine agonist (L-type) and insensitivity toward dihydropyridine antagonist (non-L-type). The L- and non-L-type single channels were observed with single-channel conductances of 16 and 19 pS at 70 mM Sr2+ and 11 and 13 pS at 5 mM Sr2+, respectively. We obtained KD estimates of 5.2 and 1.9 mM for Sr2+ for L- and non-L-type channels, respectively. At Ca2+ concentration of ∼2 mM, the single-channel conductances of Sr2+ for the L-type channel was ∼1.5 and 4.0 pS for the non-L-type channels. Thus the limits of single-channel microdomain at the membrane potential of a hair cell (e.g., −65 mV) for Sr2+ ranges from 800 to 2,000 ion/ms, assuming an ECa of 100 mV. The channels are ≥4-fold more sensitive at the physiological concentration ranges than at concentrations >10 mM. Additionally, the channels have the propensity to dwell in the closed state at high concentrations of Sr2+, which is reflected in the time constant of the first latency distributions. It is concluded that the concentration of the permeant ion modulates the gating of hair cell Ca2+ channels. Finally, the closed state/s that is/are altered by high concentrations of Sr2+ may represent divalent ion-dependent inactivation of the L-type channel.

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Multiple time-point assessment of lncRNA MEG3 shows potential to monitor treatment efficacy in rheumatoid arthritis patients

Biomarkers in Medicine ◽

10.2217/bmm-2021-0070 ◽

2021 ◽

Author(s):

Zehui Wang ◽

Weiyong Zhang ◽

Shouxia Li ◽

Dingli Chen ◽

Lei Wang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Peripheral Blood ◽

Treatment Efficacy ◽

Multiple Time ◽

Clinical Role ◽

Multiple Time Point ◽

Potential Biomarker ◽

Monitoring Treatment ◽

Time Point

Background: This study explored the clinical role of lncRNA MEG3 in rheumatoid arthritis (RA) management. Materials & methods: Totally, 191 active RA patients were enrolled, and their lncRNA MEG3 expressions in peripheral blood monoclonal cells were detected. Results: LncRNA MEG3 expression was downregulated, and it negatively correlated with lesion joints, inflammation and disease activity in RA patients. Moreover, lncRNA MEG3 expression was increased during treatment; meanwhile its increment correlated with treatment response and remission. Conclusion: LncRNA MEG3 may serve as a potential biomarker for monitoring treatment efficacy in RA management.

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Bidirectional saturable transport of LHRH across the blood-brain barrier

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.261.3.e312 ◽

1991 ◽

Vol 261 (3) ◽

pp. E312-E318 ◽

Cited By ~ 4

Author(s):

C. M. Barrera ◽

A. J. Kastin ◽

M. B. Fasold ◽

W. A. Banks

Keyword(s):

Blood Brain Barrier ◽

Ovarian Function ◽

Brain Barrier ◽

Multiple Time ◽

Blood Brain ◽

Permeability Surface ◽

Cerebrovascular Permeability ◽

The Difference ◽

Single Time Point ◽

Time Point

Systemic administration of luteinizing hormone-releasing hormone (LHRH) in rats has been found to influence behavior independently of pituitary or ovarian function. A previous study has shown that LHRH can cross the blood-brain barrier in one direction, but it was not known whether this was due to a saturable transport system. The rate of entry of 125I-labeled LHRH from blood to brain was determined by two different single-pass methods of carotid perfusion. The first, a multiple time point method, measures Ki from the slope of the linear regression when brain-to-blood ratios of radioiodinated LHRH are plotted against time. Saturable transport was determined by the difference between the Ki of rats perfused with 125I-LHRH (12.51 X 10(-3) mg.g-1.min-1) vs. rats perfused with 125I-LHRH and unlabeled LHRH (10 nmol/ml; 2.20 X 10(-3) ml.g-1.min-1). The inhibition by the unlabeled peptide was statistically significant (P less than 0.001). The second method, a single time point technique, measures the cerebrovascular permeability-surface area coefficient (PA). Saturable transport was determined in rats by the competition of unlabeled LHRH with 125I-LHRH. The PA value for 125I-LHRH (20.00 X 10(-3) ml.g-1.min-1) was significantly greater (P less than 0.05) than for 125I-LHRH with the addition of 10 nmol/ml unlabeled LHRH (4.14 X 10(-3) ml.g-1.min-1). Saturable transport of LHRH from brain to blood in mice was also determined.(ABSTRACT TRUNCATED AT 250 WORDS)

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Interactions of a Reversible Ryanoid (21-Amino-9α-Hydroxy-Ryanodine) with Single Sheep Cardiac Ryanodine Receptor Channels

The Journal of General Physiology ◽

10.1085/jgp.112.1.55 ◽

1998 ◽

Vol 112 (1) ◽

pp. 55-69 ◽

Cited By ~ 35

Author(s):

Bhavna Tanna ◽

William Welch ◽

Luc Ruest ◽

John L. Sutko ◽

Alan J. Williams

Keyword(s):

Sarcoplasmic Reticulum ◽

Binding Site ◽

Single Channel ◽

Single Channels ◽

Open Probability ◽

Release Channel ◽

Cardiac Sarcoplasmic Reticulum ◽

Channel Protein ◽

High Affinity ◽

Conductance State

The binding of ryanodine to a high affinity site on the sarcoplasmic reticulum Ca2+-release channel results in a dramatic alteration in both gating and ion handling; the channel enters a high open probability, reduced-conductance state. Once bound, ryanodine does not dissociate from its site within the time frame of a single channel experiment. In this report, we describe the interactions of a synthetic ryanoid, 21-amino-9α-hydroxy-ryanodine, with the high affinity ryanodine binding site on the sheep cardiac sarcoplasmic reticulum Ca2+-release channel. The interaction of 21-amino-9α-hydroxy-ryanodine with the channel induces the occurrence of a characteristic high open probability, reduced-conductance state; however, in contrast to ryanodine, the interaction of this ryanoid with the channel is reversible under steady state conditions, with dwell times in the modified state lasting seconds. By monitoring the reversible interaction of this ryanoid with single channels under voltage clamp conditions, we have established a number of novel features of the ryanoid binding reaction. (a) Modification of channel function occurs when a single molecule of ryanoid binds to the channel protein. (b) The ryanoid has access to its binding site only from the cytosolic side of the channel and the site is available only when the channel is open. (c) The interaction of 21-amino-9α-hydroxy-ryanodine with its binding site is influenced strongly by transmembrane voltage. We suggest that this voltage dependence is derived from a voltage-driven conformational alteration of the channel protein that changes the affinity of the binding site, rather than the translocation of the ryanoid into the voltage drop across the channel.

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BARcode DEmixing through Non-negative Spatial Regression (BarDensr)

PLoS Computational Biology ◽

10.1371/journal.pcbi.1008256 ◽

2021 ◽

Vol 17 (3) ◽

pp. e1008256

Author(s):

Shuonan Chen ◽

Jackson Loper ◽

Xiaoyin Chen ◽

Alex Vaughan ◽

Anthony M. Zador ◽

...

Keyword(s):

State Of The Art ◽

Spatial Regression ◽

Image Data ◽

Real Data ◽

Optimization Methods ◽

Spatial Density ◽

Signal Recovery ◽

Cloud Platform ◽

Rna Transcripts ◽

Different Types

Modern spatial transcriptomics methods can target thousands of different types of RNA transcripts in a single slice of tissue. Many biological applications demand a high spatial density of transcripts relative to the imaging resolution, leading to partial mixing of transcript rolonies in many voxels; unfortunately, current analysis methods do not perform robustly in this highly-mixed setting. Here we develop a new analysis approach, BARcode DEmixing through Non-negative Spatial Regression (BarDensr): we start with a generative model of the physical process that leads to the observed image data and then apply sparse convex optimization methods to estimate the underlying (demixed) rolony densities. We apply BarDensr to simulated and real data and find that it achieves state of the art signal recovery, particularly in densely-labeled regions or data with low spatial resolution. Finally, BarDensr is fast and parallelizable. We provide open-source code as well as an implementation for the ‘NeuroCAAS’ cloud platform.

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Sparse Signal Recovery from Modulo Observations

10.21203/rs.3.rs-42731/v1 ◽

2020 ◽

Author(s):

Viraj Shah ◽

Chinmay Hegde

Keyword(s):

Phase Retrieval ◽

Dynamic Range ◽

Signal Reconstruction ◽

Real Data ◽

Superior Performance ◽

Signal Recovery ◽

Reconstruction Methods ◽

Novel Approach ◽

Sparsity Constraints ◽

Improved Performance

Abstract We consider the problem of reconstructing a signal from under-determined modulo observations (or measurements). This observation model is inspired by a (relatively) less well-known imaging mechanism called modulo imaging, which can be used to extend the dynamic range of imaging systems; variations of this model have also been studied under the category of phase unwrapping. Signal reconstruction in the under-determined regime with modulo observations is a challenging ill-posed problem, and existing reconstruction methods cannot be used directly. In this paper, we propose a novel approach to solving the inverse problem limited to two modulo periods, inspired by recent advances in algorithms for phase retrieval under sparsity constraints. We show that given a sufficient number of measurements, our algorithm perfectly recovers the underlying signal and provides improved performance over other existing algorithms. We also provide experiments validating our approach on both synthetic and real data to depict its superior performance.

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Effect of Auxin (IAA) on the Fast Vacuolar (FV) Channels in Red Beet (Beta vulgaris L.) Taproot Vacuoles

International Journal of Molecular Sciences ◽

10.3390/ijms21144876 ◽

2020 ◽

Vol 21 (14) ◽

pp. 4876

Author(s):

Zbigniew Burdach ◽

Agnieszka Siemieniuk ◽

Waldemar Karcz

Keyword(s):

Single Channel ◽

Outward Current ◽

K Channel ◽

Single Channels ◽

Patch Clamp Technique ◽

Open Probability ◽

Inward Current ◽

Bath Solution ◽

Outward Currents ◽

Inward Currents

In contrast to the well-studied effect of auxin on the plasma membrane K+ channel activity, little is known about the role of this hormone in regulating the vacuolar K+ channels. Here, the patch-clamp technique was used to investigate the effect of auxin (IAA) on the fast-activating vacuolar (FV) channels. It was found that the macroscopic currents displayed instantaneous currents, which at the positive potentials were about three-fold greater compared to the one at the negative potentials. When auxin was added to the bath solution at a final concentration of 1 µM, it increased the outward currents by about 60%, but did not change the inward currents. The imposition of a ten-fold vacuole-to-cytosol KCl gradient stimulated the efflux of K+ from the vacuole into the cytosol and reduced the K+ current in the opposite direction. The addition of IAA to the bath solution with the 10/100 KCl gradient decreased the outward current and increased the inward current. Luminal auxin reduced both the outward and inward current by approximately 25% compared to the control. The single channel recordings demonstrated that cytosolic auxin changed the open probability of the FV channels at the positive voltages to a moderate extent, while it significantly increased the amplitudes of the single channel outward currents and the number of open channels. At the positive voltages, auxin did not change the unitary conductance of the single channels. We suggest that auxin regulates the activity of the fast-activating vacuolar (FV) channels, thereby causing changes of the K+ fluxes across the vacuolar membrane. This mechanism might serve to tightly adjust the volume of the vacuole during plant cell expansion.

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