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Biophysics Reviews Jun 2024Microelectrode recordings from human peripheral and cranial nerves provide a means to study both afferent and efferent axonal signals at different levels of detail, from...
Microelectrode recordings from human peripheral and cranial nerves provide a means to study both afferent and efferent axonal signals at different levels of detail, from multi- to single-unit activity. Their analysis can lead to advancements both in diagnostic and in the understanding of the genesis of neural disorders. However, most of the existing computational toolboxes for the analysis of microneurographic recordings are limited in scope or not open-source. Additionally, conventional burst-based metrics are not suited to analyze pathological conditions and are highly sensitive to distance of the microelectrode tip from the active axons. To address these challenges, we developed an open-source toolbox that offers advanced analysis capabilities for studying neuronal reflexes and physiological responses to peripheral nerve activity. Our toolbox leverages the observation of temporal sequences of action potentials within inherently cyclic signals, introducing innovative methods and indices to enhance analysis accuracy. Importantly, we have designed our computational toolbox to be accessible to novices in biomedical signal processing. This may include researchers and professionals in healthcare domains, such as clinical medicine, life sciences, and related fields. By prioritizing user-friendliness, our software application serves as a valuable resource for the scientific community, allowing to extract advanced metrics of neural activity in short time and evaluate their impact on other physiological variables in a consistent and standardized manner, with the final aim to widen the use of microneurography among researchers and clinicians.
PubMed: 38895135
DOI: 10.1063/5.0202385 -
Cell Death & Disease Jun 2024Tauopathies are characterised by the pathological accumulation of misfolded tau. The emerging view is that toxic tau species drive synaptic dysfunction and potentially...
Tauopathies are characterised by the pathological accumulation of misfolded tau. The emerging view is that toxic tau species drive synaptic dysfunction and potentially tau propagation before measurable neurodegeneration is evident, but the underlying molecular events are not well defined. Human non-mutated 0N4R tau (tau) and P301L mutant 0N4R tau (tau) were expressed in mouse primary cortical neurons using adeno-associated viruses to monitor early molecular changes and synaptic function before the onset of neuronal loss. In this model tau was differentially phosphorylated relative to tau with a notable increase in phosphorylation at ser262. Affinity purification - mass spectrometry combined with tandem mass tagging was used to quantitatively compare the tau and tau interactomes. This revealed an enrichment of tau with ribosomal proteins but a decreased interaction with the proteasome core complex and reduced tau degradation. Differences in the interaction of tau with members of a key synaptic calcium-calmodulin signalling pathway were also identified, most notably, increased association with CaMKII but reduced association with calcineurin and the candidate AD biomarker neurogranin. Decreased association of neurogranin to tau corresponded with the appearance of enhanced levels of extracellular neurogranin suggestive of potential release or leakage from synapses. Finally, analysis of neuronal network activity using micro-electrode arrays showed that overexpression of tau promoted basal hyperexcitability coincident with these changes in the tau interactome and implicating tau in specific early alterations in synaptic function.
Topics: Animals; tau Proteins; Humans; Mice; Neurons; Phosphorylation; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Tauopathies; Synapses; Neurogranin; Calcineurin
PubMed: 38890273
DOI: 10.1038/s41419-024-06815-2 -
Operative Neurosurgery (Hagerstown, Md.) Jun 2024Long-term outcomes in deep brain stimulation (DBS) depend on accuracy of lead placement. Microelectrode recording (MER) is a long-used adjunct to leverage...
BACKGROUND AND OBJECTIVES
Long-term outcomes in deep brain stimulation (DBS) depend on accuracy of lead placement. Microelectrode recording (MER) is a long-used adjunct to leverage neurophysiological information to confirm satisfactory trajectory of implanted electrodes. The goal of this study was to evaluate the consistency in which electrodes are placed in sampled microelectrode trajectories.
METHODS
This is a retrospective study using intraoperative computed tomography to measure final electrode deviation from MER probe placement during the DBS insertion targeting subthalamic nucleus. Fifteen patients had 29 DBS leads placed using MER assistance. Radial distance between the probe and the lead were measured for each patient using intraoperative imaging. In addition, the preoperative target to final lead error was measured in 14 patients undergoing subthalamic nucleus implants without the use of MER and compared with the 15 patients in which MER was used as an adjunct.
RESULTS
There was no significant difference in the mean radial target error (1.2 vs 1.0 mm, P = .156) when comparing the leads placed with or without MER assistance, respectively. The mean difference in final position of microelectrode compared with DBS lead was 0.9 ± 0.1 (range 0.4-2.0 mm). Of all MER-assisted electrodes placed, 44.8% (13) of electrode final positions radially deviated 1.0 mm or more from the MER probe.
CONCLUSION
Electrode placement may deviate significantly from MER trajectories. Given the concern that physiological data may not be representative of the final electrode trajectory, surgeons should consider using intraoperative imaging or other adjunctive techniques during DBS to confirm accuracy and satisfactory trajectory of DBS leads.
PubMed: 38888341
DOI: 10.1227/ons.0000000000001224 -
Frontiers in Cell and Developmental... 2024Osseointegration commences with foreign body inflammation upon implant placement, where macrophages play a crucial role in the immune response. Subsequently, during the...
Osseointegration commences with foreign body inflammation upon implant placement, where macrophages play a crucial role in the immune response. Subsequently, during the intermediate and late stages of osseointegration, mesenchymal stem cells (MSCs) migrate and initiate their osteogenic functions, while macrophages support MSCs in osteogenesis. The utilization of ferroelectric P(VDF-TrFE) covered ITO planar microelectrodes facilitated the simulation of various surface charge to investigate their effects on MSCs' osteogenic differentiation and macrophage polarization and the results indicated a parabolic increase in the promotional effect of both with the rise in piezoelectric coefficient. Furthermore, the surface charge with a piezoelectric coefficient of -18 exhibited the strongest influence on the promotion of M1 polarization of macrophages and the promotion of MSCs' osteogenic differentiation. The impact of macrophage polarization and MSC osteogenesis following the interaction of macrophages affected by surface charge and MSC was ultimately investigated. It was observed that macrophages affected by the surface charge of -18 piezoelectric coefficient still exerted the most profound induced osteogenic effect, validating the essential role of M1-type macrophages in the osteogenic differentiation of MSCs.
PubMed: 38887522
DOI: 10.3389/fcell.2024.1401917 -
Nature Communications Jun 2024Despite decades of research, we still do not understand how spontaneous human seizures start and spread - especially at the level of neuronal microcircuits. In this...
Despite decades of research, we still do not understand how spontaneous human seizures start and spread - especially at the level of neuronal microcircuits. In this study, we used laminar arrays of micro-electrodes to simultaneously record the local field potentials and multi-unit neural activities across the six layers of the neocortex during focal seizures in humans. We found that, within the ictal onset zone, the discharges generated during a seizure consisted of current sinks and sources only within the infra-granular and granular layers. Outside of the seizure onset zone, ictal discharges reflected current flow in the supra-granular layers. Interestingly, these patterns of current flow evolved during the course of the seizure - especially outside the seizure onset zone where superficial sinks and sources extended into the deeper layers. Based on these observations, a framework describing cortical-cortical dynamics of seizures is proposed with implications for seizure localization, surgical targeting, and neuromodulation techniques to block the generation and propagation of seizures.
Topics: Humans; Seizures; Neocortex; Male; Electroencephalography; Adult; Female; Young Adult; Cerebral Cortex; Microelectrodes; Neurons
PubMed: 38886376
DOI: 10.1038/s41467-024-48746-8 -
Journal of Neural Engineering Jun 2024Brain-computer interfaces (BCIs) are technologies that bypass damaged or disrupted neural pathways and directly decode brain signals to perform intended actions. BCIs...
Brain-computer interfaces (BCIs) are technologies that bypass damaged or disrupted neural pathways and directly decode brain signals to perform intended actions. BCIs for speech have the potential to restore communication by decoding the intended speech directly. Many studies have demonstrated promising results using invasive micro-electrode arrays and electrocorticography. However, the use of stereo-electroencephalography (sEEG) for speech decoding has not been fully recognized.In this research, recently released sEEG data were used to decode Dutch words spoken by epileptic participants. We decoded speech waveforms from sEEG data using advanced deep-learning methods. Three methods were implemented: a linear regression method, an recurrent neural network (RNN)-based sequence-to-sequence model (RNN), and a transformer model.Our RNN and transformer models outperformed the linear regression significantly, while no significant difference was found between the two deep-learning methods. Further investigation on individual electrodes showed that the same decoding result can be obtained using only a few of the electrodes.This study demonstrated that decoding speech from sEEG signals is possible, and the location of the electrodes is critical to the decoding performance.
Topics: Humans; Deep Learning; Electroencephalography; Speech; Brain-Computer Interfaces; Male; Female; Epilepsy; Stereotaxic Techniques; Adult; Neural Networks, Computer
PubMed: 38885688
DOI: 10.1088/1741-2552/ad593a -
Journal of Neural Engineering Jul 2024The wireless transfer of power for driving implantable neural stimulation devices has garnered significant attention in the bioelectronics field. This study explores the...
The wireless transfer of power for driving implantable neural stimulation devices has garnered significant attention in the bioelectronics field. This study explores the potential of photovoltaic (PV) power transfer, utilizing tissue-penetrating deep-red light-a novel and promising approach that has received less attention compared to traditional induction or ultrasound techniques. Our objective is to critically assess key parameters for directly powering neurostimulation electrodes with PVs, converting light impulses into neurostimulation currents.We systematically investigate varying PV cell size, optional series configurations, and coupling with microelectrodes fabricated from a range of materials such as Pt, TiN, IrO, Ti, W, PtO, Au, or poly(3,4 ethylenedioxythiophene):poly(styrene sulfonate). Additionally, two types of PVs, ultrathin organic PVs and monocrystalline silicon PVs, are compared. These combinations are employed to drive pairs of electrodes with different sizes and impedances. The readout method involves measuring electrolytic current using a straightforward amplifier circuit.Optimal PV selection is crucial, necessitating sufficiently large PV cells to generate the desired photocurrent. Arranging PVs in series is essential to produce the appropriate voltage for driving current across electrode/electrolyte impedances. By carefully choosing the PV arrangement and electrode type, it becomes possible to emulate electrical stimulation protocols in terms of charge and frequency. An important consideration is whether the circuit is photovoltage-limited or photocurrent-limited. High charge-injection capacity electrodes made from pseudo-faradaic materials impose a photocurrent limit, while more capacitive materials like Pt are photovoltage-limited. Although organic PVs exhibit lower efficiency than silicon PVs, in many practical scenarios, stimulation current is primarily limited by the electrodes rather than the PV driver, leading to potential parity between the two types.This study provides a foundational guide for designing a PV-powered neurostimulation circuit. The insights gained are applicable to bothandapplications, offering a resource to the neural engineering community.
Topics: Electrodes, Implanted; Microelectrodes; Equipment Design; Implantable Neurostimulators; Electric Stimulation
PubMed: 38885680
DOI: 10.1088/1741-2552/ad593d -
Journal of Neural Engineering Jun 2024Study of the foreign body reaction to implanted electrodes in the brain is an important area of research for the future development of neuroprostheses and experimental...
Study of the foreign body reaction to implanted electrodes in the brain is an important area of research for the future development of neuroprostheses and experimental electrophysiology. After electrode implantation in the brain, microglial activation, reactive astrogliosis, and neuronal cell death create an environment immediately surrounding the electrode that is significantly altered from its homeostatic state. To uncover physiological changes potentially affecting device function and longevity, spatial transcriptomics was implemented to identify changes in gene expression driven by electrode implantation and compare this differential gene expression to traditional metrics of glial reactivity, neuronal loss, and electrophysiological recording quality. For these experiments, rats were chronically implanted with functional Michigan-style microelectrode arrays, from which electrophysiological recordings (multi-unit activity, local field potential) were taken over a six-week time course. Brain tissue cryosections surrounding each electrode were then mounted for spatial transcriptomics processing. The tissue was immunolabeled for neurons and astrocytes, which provided both a spatial reference for spatial transcriptomics and a quantitative measure of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) immunolabeling surrounding each implant. Results from rat motor cortex within 300µm of the implanted electrodes at 24 hours, 1 week, and 6 weeks post-implantation showed up to 553 significantly differentially expressed (DE) genes between implanted and non-implanted tissue sections. Regression on the significant DE genes identified the 6-7 genes that had the strongest relationship to histological and electrophysiological metrics, revealing potential candidate biomarkers of recording quality and the tissue response to implanted electrodes .
PubMed: 38885679
DOI: 10.1088/1741-2552/ad5936 -
IEEE Transactions on Biomedical... Jun 2024Electrical capacitance tomography (ECT) can be used to predict information about the interior volume of an object based on measured capacitance at its boundaries. Here,...
Electrical capacitance tomography (ECT) can be used to predict information about the interior volume of an object based on measured capacitance at its boundaries. Here, we present a microscale capacitance tomography system with a spatial resolution of 10 microns using an active CMOS microelectrode array. We introduce a deep learning model for reconstructing 3-D volumes of cell cultures using the boundary capacitance measurements acquired from the sensor array, which is trained using a multi-objective loss function that combines a pixel-wise loss function, a distribution-based loss function, and a region-based loss function to improve model's reconstruction accuracy. The multi-objective loss function enhances the model's reconstruction accuracy by 3.2% compared to training only with a pixel-wise loss function. Compared to baseline computational methods, our model achieves an average of 4.6% improvement on the datasets evaluated. We demonstrate our approach on experimental datasets of bacterial biofilms, showcasing the system's ability to resolve microscopic spatial features of cell cultures in three dimensions. Microscale capacitance tomography can be a low-cost, low-power, label-free tool for 3-D imaging of biological samples.
PubMed: 38885101
DOI: 10.1109/TBCAS.2024.3415360 -
ACS Applied Materials & Interfaces Jun 2024Electrode/electrolyte interfacial ion transfer is a fundamental process occurring during insertion-type redox reactions at battery electrodes. The rate at which ions...
Electrode/electrolyte interfacial ion transfer is a fundamental process occurring during insertion-type redox reactions at battery electrodes. The rate at which ions move into and out of the electrode, as well as at interphase structures, directly impacts the power performance of the battery. However, measuring and quantifying these ion transfer phenomena can be difficult, especially at high electrolyte concentrations as found in batteries. Herein, we report a scanning electrochemical microscope method using a common ferri/ferrocyanide (FeCN) redox mediator dissolved in an aqueous electrolyte to track changes in alkali ions at high electrolyte concentrations (up to 3 mol dm). Using voltammetry at a platinum microelectrode, we observed a reversible shift of ∼60 mV per decade change in K concentrations. The response showed high stability in sequential measurements and similar behavior in other aqueous electrolytes. From there, we used the same FeCN mediator to position the microelectrode at the surface of a potassium-insertion electrode. We demonstrate tracking of local changes in the K concentration during insertion and deinsertion processes. Using a 2D axisymmetric, finite element model, we further estimate the effective insertion rates. These developments enable characterization of a key parameter for improving batteries, the interfacial ion transfer kinetics, and future work may show mediators appropriate for molar concentrations in nonaqueous electrolytes and beyond.
PubMed: 38885040
DOI: 10.1021/acsami.4c03645