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Clinical relevance- This work informs the use of micro-computed tomography as a tool for correlating neural device performance with physical attributes of the implant location.High Frequency Oscillations (HFOs, 200-600 Hz) are recognized as a biomarker of epileptogenic brain areas. This work aims at designing novel microelectrodes in order to optimize the recording and further detection of HFOs in brain (intracerebral electroencephalography, iEEG). The quality of the recorded iEEG signals is highly dependent on the electrode contact impedance, which is determined by the characteristics of the recording electrode (geometry, position, material). These properties are essential for the observability of HFOs. In this study, a previously published hippocampal neural network model is used for the simulation of interictal HFOs. Bay 11-7085 An additional microelectrode model layer is implemented in order to simulate the impact of using different types and characteristics of microelectrodes on the recorded HFOs. Results indicate that a small layer PEDOT/PSS and PEDOT/CNT on microelectrodes can effectively decrease their impedance resulting in the increase of HFOs observability. This model-based study can lead to the actual design of new electrodes that will ultimately contribute to improved diagnosis prior to invasive therapies.We present MAPSYNE, a miniaturized and automated system combining a high-density microelectrode array (HD-MEA) and a movable micropipette for studying, monitoring, and perturbing neurons in vitro. The system involves an all-electrical approach to automatically move a glass micropipette towards a target location on the HD-MEA surface, without the need for a microscope. Two methods of performing blind navigation are employed, (i) stop-measure-go approach wherein the pipette moves for a predefined distance before measuring its location then the process is repeated until the pipette reaches its destination, and (ii) predictive approach wherein the pipette is continuously tracked and moved. This automated system can be applied for unsupervised single-cell manipulation of neurons in a network, such as electroporation and local delivery of compounds.Brain Computer Interfaces (BCIs) allow individuals to control devices, machines and prostheses with their thoughts. Most feasibility studies with BCIs have utilized scalp electroencephalography (EEG), due to it being accessible, noninvasive, and portable. While BCIs have been studied with magnetoencephalography (MEG), the modality has limited applications due to the large immobile hardware. Here we propose that room-temperature, optically-pumped magnetometers (OPMs) can potentially serve a portable modality that can be used for BCIs. OPMs have the added advantage that low-frequency neuromagnetic fields are not affected by volume conduction, which is known to distort EEG signals. In this feasibility study, we tested an OPM system with a real-time BCI where able bodied participants controlled a cursor to reach two targets. This BCI system used alpha and beta-band power modulations associated with hand movements. Our preliminary results show significant alpha and beta-band desynchronization due to movement, as found in previous literature.Magnetomyography (MMG) is the measurement of magnetic signals generated in the skeletal muscle of humans by electrical activities. However, current technologies developed to detect such tiny magnetic field are bulky, costly and require working at the temperature-controlled environment. Developing a miniaturized, low cost and room temperature magnetic sensors provide an avenue to enhance this research field. Herein, we present an integrated tunnelling magnetoresistive (TMR) array for room temperature MMG applications. TMR sensors were developed with low-noise analogue front-end circuitry to detect the MMG signals without and with averaging at a high signal-to-noise ratio. The MMG was achieved by averaging signals using the Electromyography (EMG) signal as a trigger. Amplitudes of 200 pT and 30 pT, corresponding to periods when the hand is tense and relaxed, were observed, which is consistent with muscle simulations based on finite-element method (FEM) considering the effect of distance from the observation point to the magnetic field source.In this paper, a power-efficient and high-resolution ultrasonically powered and controlled optogenetic stimulator system is proposed. The proposed system benefits from a novel fully analog Time to Current Converter (TCC) for driving a μLED for optogenetics according to time-encoded data over ultrasonic waves. The whole system including a high-efficiency active rectifier, a double-pass regulator, a burst detector, an overvoltage regulator, a reference generator and the novel TCC are designed, analyzed and simulated in transistor level in standard TSMC 0.18 μm CMOS technology in conjunction with a lumped-element model for the piezoelectric receiver. For an LED current of 1 mA, a chip efficiency of 94 % is achieved according to the simulation results. The rectified voltage at the output of the active rectifier is equal to 2.85 V for a 1 mA load and is limited to 3.02 V by the overvoltage regulator, for loads of less than 905 μA. The proposed TCC demands only 0.2 V overhead voltage and specifically designed to converts the time duration between 5-55 μs to a current of 0-1000 μA linearly and according to the application requirements.Chronic stability of functional performance is a significant challenge to the success of implantable devices for neural stimulation and recording. Integrating wireless technology with typical microelectrode array designs is one approach that may reduce instances of mechanical failure and improve the long-term performance of neural devices. We have investigated the long-term stability of Wireless Floating Microelectrode Arrays (WMFAs) implanted in rat sciatic nerve, and their ability to selectively recruit muscles in the hind limb via neural stimulation. Thresholds as low as 4.1 μA were able to generate visible motion of the rear paw. Each implanted device (n=6) was able to selectively recruit plantar flexion and dorsiflexion of the rear paw, and selective stimulation of both movements was achieved throughout the study period. The evoked limb motion was electrode specific and was dependent on location within the fascicular structure of the nerve. Motor thresholds and movement patterns remained stable for more than 8 weeks after device implantation. No major changes in limb function were observed between the implanted and contralateral limb, or between implanted animals and control group animals. The results of this study show that WFMAs with intrafascicular electrodes implanted in a healthy peripheral nerve can provide stable and selective motor recruitment, without altering overall limb function.Optical recording of genetically encoded calcium indicator (GECI) allows neuroscientists to study the activity of genetically labeled neuron populations, but our current tools lack the resolution, stability and are often too invasive. Here we present the design concepts, prototypes, and preliminary measurement results of a super-miniaturized wireless image sensor built using a 32nm Silicon-on-Insulator process. SOI process is optimal for wireless applications, and we can further thin the substrate to reduce overall device thickness to ~25μm and operate the pixels using back-side illumination. The proposed device is 300μm × 300μm. Our prototype is built on a 3 × 3mm die.Parylene-C has been used as a substrate and encapsulation material for many implantable medical devices. However, to ensure the flexibility required in some applications, minimize tissue reaction, and protect parylene from degradation in vivo an additional outmost layer of polydimethylsiloxane (PDMS) is desired. In such a scenario, the adhesion of PDMS to parylene is of critical importance to prevent early failure caused by delamination in the harsh environment of the human body. Towards this goal, we propose a method based on creating chemical covalent bonds using intermediate ceramic layers as adhesion promoters between PDMS and parylene.To evaluate our concept, we prepared three different sets of samples with PDMS on parylene without and with oxygen plasma treatment (the most commonly employed method to increase adhesion), and samples with our proposed ceramic intermediate layers of silicon carbide (SiC) and silicon dioxide (SiO2). The samples were soaked in phosphate-buffered saline (PBS) solution at room temperature and were inspected under an optical microscope. To investigate the adhesion property, cross-cut tape tests and peel tests were performed. The results showed a significant improvement of the adhesion and in-soak long-term performance of our proposed encapsulation stack compared with PDMS on parylene and PDMS on plasma-treated parylene. We aim to use the proposed solution to package bare silicon chips on active implants.Electrical stimulation of surviving retinal neurons has proven effective in restoring sight to totally blind patients affected by retinal degenerative diseases. Morphological and biophysical differences among retinal ganglion cells (RGCs) are important factors affecting their response to epiretinal electrical stimulation. Although detailed models of ON and OFF RGCs have already been investigated, here we developed morphologically and biophysically realistic computational models of two classified RGCs, D1-bistratified and A2-monostratified, and analyzed their response to alternations in stimulation frequency (up to 200 Hz). Results show that the D1-bistratified cell is more responsive to high frequency stimulation compared to the A2-monostratified cell. This differential RGCs response suggests a potential avenue for selective activation, and in turn different encoded percept of RGCs.This paper reports on the customized thinning of neural probes based on silicon (Si) using deep reactive ion etching (DRIE) as a post-processing step. The reduced probe dimensions are expected to minimize local tissue trauma, while guaranteeing probe integrity during implantation. For DRIE, the probes are partially masked by a micromachined Si cover chip comprising tailored cavities enabling any desired thinned length l and probe thickness t by a proper choice of cover chip design and DRIE parameters, respectively. A broad variety of probe designs were realized with shank tip thicknesses ranging from 35 µm down to 2 µm. All probes could successfully be implanted into a brain tissue phantom, demonstrating a pronounced reduction in insertion force from 0.55 mN for unprocessed probes to 0.08 mN for 2-µm-thin shanks. When the dura mater was mimicked by a polyethylene (PE) membrane, forces were reduced from 28.9 mN to 16.6 mN for 15-µm-thin shanks.Vagus nerve stimulation (VNS) is a neurostimulation therapy for epilepsy and severe depression and has been recently shown to be effective for other conditions. Despite its demonstrated safety and efficacy, long-term and off-target effects of VNS remain to be fully determined. One of the complications reported in epilepsy is stimulation-induced sleep abnormalities. As epilepsy itself can impact sleep quality, contribution of VNS alone in such off-target effects remain mainly unknown. In this study, we analyzed data from long-term VNS experiments in rats to characterize effects of VNS on circadian rhythms derived from heart rate and heart rate variability (HRV). We have also explored possible sex differences in long-term effects of VNS on intrinsic biological rhythms. Compared with control animals, significant VNS-induced changes in circadian rhythms were observed particularly in female rats over 24h and 6h light cycles (1PM-7PM). These findings enhance our understanding of VNS contribution and biological sex role on sleep difficulties reported by using VNS therapy.

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