Single neurons in the thalamus and subthalamic nucleus process cardiac and respiratory signals in humans.

Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at the cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: ventral intermedius nucleus (Vim) and ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. A substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals.

Multisize Electrode Field-of-View: Validation by High Resolution Gadolinium-Enhanced Cardiac Magnetic Resonance.

BACKGROUND: Voltage mapping to detect ventricular scar is important for guiding catheter ablation, but the field-of-view of unipolar, bipolar, conventional, and microelectrodes as it relates to the extent of viable myocardium (VM) is not well defined. OBJECTIVES: The purpose of this study was to evaluate electroanatomic voltage-mapping (EAVM) with different-size electrodes for identifying VM, validated against high-resolution ex-vivo cardiac magnetic resonance (HR-LGE-CMR). METHODS: A total of 9 swine with early-reperfusion myocardial infarction were mapped with the QDOT microcatheter. HR-LGE-CMR (0.3-mm slices) were merged with EAVM. At each EAVM point, the underlying VM in multisize transmural cylinders and spheres was quantified from ex vivo CMR and related to unipolar and bipolar voltages recorded from conventional and microelectrodes. RESULTS: In each swine, 220 mapping points (Q1, Q3: 216, 260 mapping points) were collected. Infarcts were heterogeneous and nontransmural. Unipolar and bipolar voltage increased with VM volumes from >175 mm3 up to >525 mm3 (equivalent to a 5-mm radius cylinder with height >6.69 mm). VM volumes in subendocardial cylinders with 1- or 3-mm depth correlated poorly with all voltages. Unipolar voltages recorded with conventional and microelectrodes were similar (difference 0.17 ± 2.66 mV) and correlated best to VM within a sphere of radius 10 and 8 mm, respectively. Distance-weighting did not improve the correlation. CONCLUSIONS: Voltage increases with transmural volume of VM but correlates poorly with small amounts of VM, which limits EAVM in defining heterogeneous scar. Microelectrodes cannot distinguish thin from thick areas of subendocardial VM. The field-of-view for unipolar recordings for microelectrodes and conventional electrodes appears to be 8 to 10 mm, respectively, and unexpectedly similar.

Neuroactivity screening of botanical extracts using microelectrode array (MEA) recordings.

Toxicity testing of botanicals is challenging because of their chemical complexity and variability. Since botanicals may affect many different modes of action involved in neuronal function, we used microelectrode array (MEA) recordings of primary rat cortical cultures to screen 16 different botanical extracts for their effects on cell viability and neuronal network function in vitro. Our results demonstrate that extract materials (50 µg/mL) derived from goldenseal, milk thistle, tripterygium, and yohimbe decrease mitochondrial activity following 7 days exposure, indicative of cytotoxicity. Importantly, most botanical extracts alter neuronal network function following acute exposure. Extract materials (50 µg/mL) derived from aristolochia, ephedra, green tea, milk thistle, tripterygium, and usnea inhibit neuronal activity. Extracts of kava, kratom and yohimbe are particularly potent and induce a profound inhibition of neuronal activity at the low dose of 5 µg/mL. Extracts of blue cohosh, goldenseal and oleander cause intensification of the bursts. Aconite extract (5 µg/mL) evokes a clear hyperexcitation with a marked increase in the number of spikes and (network) bursts. The distinct activity patterns suggest that botanical extracts have diverse modes of action. Our combined data also highlight the applicability of MEA recordings for hazard identification and potency ranking of botanicals.

Difunctional Microelectrode Arrays for Single-Cell Electrical Stimulation and pH Detection.

Due to its direct effect on biomolecules and cells, electrical stimulation (ES) is now widely used to regulate cell proliferation, differentiation, and neurostimulation and is even used in the clinic for pain relief, treatment of nerve damage, and muscle rehabilitation. Conventional ES is mostly studied on cell populations, but the heterogeneity of cancer cells results in the inability to access the response of individual cells to ES. Therefore, detecting the extracellular pH change (ΔpHe) after ES at the single-cell level is important for the application of ES in tumor therapy. In this study, cellular ΔpHe after periodic impulse electrostimulation (IES) was monitored in situ by using a polyaniline (PANI)-modified gold microelectrode array. The PANI sensor had excellent sensitivity (53.68 mV/pH) and linear correlation coefficient (R2 = 0.999) over the pH range of 5.55-7.41. The cells showed different degrees of ΔpHe after the IES with different intervals and stimulation potential. A shorter pulse interval and a higher stimulation potential could effectively enhance stimulation and increase cellular ΔpHe. At 0.5 V potential stimulation, the cellular ΔpHe increased with decreasing pulse interval. However, if the pulse interval was long enough, even at a higher potential of 0.7 V, there was no significant additional ΔpHe due to the insufficient stimulus strength. Based on the above conclusions, the prepared PANI microelectrode arrays (MEAs) were capable of stimulating and detecting single cells, which contributed to the deeper application of ES in tumor therapy.

Short-Term Effects of Gamma Stimulation on Neuroinflammation at the Tissue-Electrode Interface in Motor Cortex.

OBJECTIVES: The reliability of long-term neural recordings as therapeutic interventions for motor and sensory disorders is hampered by the brain tissue response. Previous work showed that flickering light at gamma frequencies (ie, 20-50 Hz) causes enhanced microglial recruitment in the visual cortex. The effects of gamma stimulation on glial cells surrounding implanted neural electrodes are not well understood. We hypothesized that invasive stimulation in the gamma frequency band increases microglial recruitment in the short term and reduces astrogliosis at the tissue-electrode interface. MATERIALS AND METHODS: Male Long Evans rats were implanted with dual-shank silicon microelectrode arrays into the motor cortex. After implantation, rats received one hour of 40-Hz stimulation at a constant current of 10 µA using charge-balanced, biphasic pulses on one shank, and the other shank served as the nonstimulated control. Postmortem, tissue sections were stained with ectodermal dysplasia 1 (ED1) for activated microglia, glial fibrillary acidic protein (GFAP) for astrocytes, and 4',6-diamidino-2-phenylindole (DAPI) for nonspecific nuclei. Fluorescent intensity and cell number as a function of distance from the tissue-electrode interface were used to quantify all stained sections. RESULTS: Fluorescent intensity for ED1 was nearly 40% lower for control than for stimulated sites (0-500 µm away from the implant), indicating increased microglial recruitment to the stimulated site (p < 0.05). Fluorescent intensity for GFAP was >67% higher for control than for stimulated sites (0-500 µm away from the implant), indicating reduced astrogliosis at the stimulated site (p < 0.05). No differences were observed in DAPI-stained sections between conditions. CONCLUSIONS: These results suggest that short-term gamma stimulation modulates glial recruitment in the immediate vicinity of the microelectrode. Future studies will investigate the long-term effects of gamma stimulation on glial recruitment at the tissue-electrode interface as a strategy to improve long-term recording reliability.

Structural and functional changes of deep layer pyramidal neurons surrounding microelectrode arrays implanted in rat motor cortex.

Devices capable of recording or stimulating neuronal signals have created new opportunities to understand normal physiology and treat sources of pathology in the brain. However, it is possible that the tissue response to implanted electrodes may influence the nature of the signals detected or stimulated. In this study, we characterized structural and functional changes in deep layer pyramidal neurons surrounding silicon or polyimide-based electrodes implanted in the motor cortex of rats. Devices were captured in 300 µm-thick tissue slices collected at the 1 or 6 week time point post-implantation, and individual neurons were assessed using a combination of whole-cell electrophysiology and 2-photon imaging. We observed disrupted dendritic arbors and a significant reduction in spine densities in neurons surrounding devices. These effects were accompanied by a decrease in the frequency of spontaneous excitatory post-synaptic currents, a reduction in sag amplitude, an increase in spike frequency adaptation, and an increase in filopodia density. We hypothesize that the effects observed in this study may contribute to the signal loss and instability that often accompany chronically implanted electrodes. STATEMENT OF SIGNIFICANCE: Implanted electrodes in the brain can be used to treat sources of pathology and understand normal physiology by recording or stimulating electrical signals generated by local neurons. However, a foreign body response following implantation undermines the performance of these devices. While several studies have investigated the biological mechanisms of device-tissue interactions through histology, transcriptomics, and imaging, our study is the first to directly interrogate effects on the function of neurons surrounding electrodes using single-cell electrophysiology. Additionally, we provide new, detailed assessments of the impacts of electrodes on the dendritic structure and spine morphology of neurons, and we assess effects for both traditional (silicon) and newer polymer electrode materials. These results reveal new potential mechanisms of electrode-tissue interactions.

Highly Activated Neuronal Firings Monitored by Implantable Microelectrode Array in the Paraventricular Thalamus of Insomnia Rats.

Insomnia is a common sleep disorder around the world, which is harmful to people's health, daily life, and work. The paraventricular thalamus (PVT) plays an essential role in the sleep-wake transition. However, high temporal-spatial resolution microdevice technology is lacking for accurate detection and regulation of deep brain nuclei. The means for analyzing sleep-wake mechanisms and treating sleep disorders are limited. To detect the relationship between the PVT and insomnia, we designed and fabricated a special microelectrode array (MEA) to record electrophysiological signals of the PVT for insomnia and control rats. Platinum nanoparticles (PtNPs) were modified onto an MEA, which caused the impedance to decrease and improved the signal-to-noise ratio. We established the model of insomnia in rats and analyzed and compared the neural signals in detail before and after insomnia. In insomnia, the spike firing rate was increased from 5.48 ± 0.28 spike/s to 7.39 ± 0.65 spike/s, and the power of local field potential (LFP) decreased in the delta frequency band and increased in the beta frequency band. Furthermore, the synchronicity between PVT neurons declined, and burst-like firing was observed. Our study found neurons of the PVT were more activated in the insomnia state than in the control state. It also provided an effective MEA to detect the deep brain signals at the cellular level, which conformed with macroscopical LFP and insomnia symptoms. These results laid the foundation for studying PVT and the sleep-wake mechanism and were also helpful for treating sleep disorders.

A highly selective and sensitive sensor for promethazine based on molecularly imprinted interface coated Au/Sn bimetal nanoclusters functionalized acupuncture needle microelectrode.

Promethazine (PMZ) is an effective antihistamine that is used as a nerve tranquilizer to treat mental disorders. However, drug abuse causes harm to the human body and also pollutes the environment to a certain extent. Therefore, it is crucial to develop a highly selective and sensitive biosensor for PMZ determination. An acupuncture needle (AN) was used as an electrode in 2015, and further research on the electrode's essence in electrochemistry is needed. In this work, a sensor based on a surface imprinted film coordinated Au/Sn biometal was first fabricated on AN via electrochemistry. The obtained cavities showed complementary and suitable sites for "N atom" electron transfer through the phenyl ring structure in promethazine, which is rigorous for the configuration near the interface. Under the optimal conditions, MIP/Au/Sn/ANE exhibits a good linear relationship in the range of 0.5 µM-500 µM, and the detection limit (LOD) is 0.14 µM (S/N = 3). The sensor exhibits good repeatability, stability, and selectivity and can be successfully used to analyze and detect PMZ in human serum and environmental water. The findings are scientifically significant for AN electrochemistry and the sensors have potential for in vivo medicamentosus monitoring in the future.

Proof of Concept for Sustainable Manufacturing of Neural Electrode Array for In Vivo Recording.

Increasing requirements for neural implantation are helping to expand our understanding of nervous systems and generate new developmental approaches. It is thanks to advanced semiconductor technologies that we can achieve the high-density complementary metal-oxide-semiconductor electrode array for the improvement of the quantity and quality of neural recordings. Although the microfabricated neural implantable device holds much promise in the biosensing field, there are some significant technological challenges. The most advanced neural implantable device relies on complex semiconductor manufacturing processes, which are required for the use of expensive masks and specific clean room facilities. In addition, these processes based on a conventional photolithography technique are suitable for mass production, which is not applicable for custom-made manufacturing in response to individual experimental requirements. The microfabricated complexity of the implantable neural device is increasing, as is the associated energy consumption, and corresponding emissions of carbon dioxide and other greenhouse gases, resulting in environmental deterioration. Herein, we developed a fabless fabricated process for a neural electrode array that was simple, fast, sustainable, and customizable. An effective strategy to produce conductive patterns as the redistribution layers (RDLs) includes implementing microelectrodes, traces, and bonding pads onto the polyimide (PI) substrate by laser micromachining techniques combined with the drop coating of the silver glue to stack the laser grooving lines. The process of electroplating platinum on the RDLs was performed to increase corresponding conductivity. Sequentially, Parylene C was deposited onto the PI substrate to form the insulation layer for the protection of inner RDLs. Following the deposition of Parylene C, the via holes over microelectrodes and the corresponding probe shape of the neural electrode array was also etched by laser micromachining. To increase the neural recording capability, three-dimensional microelectrodes with a high surface area were formed by electroplating gold. Our eco-electrode array showed reliable electrical characteristics of impedance under harsh cyclic bending conditions of over 90 degrees. For in vivo application, our flexible neural electrode array demonstrated more stable and higher neural recording quality and better biocompatibility as well during the 2-week implantation compared with those of the silicon-based neural electrode array. In this study, our proposed eco-manufacturing process for fabricating the neural electrode array reduced 63 times of carbon emissions compared to the traditional semiconductor manufacturing process and provided freedom in the customized design of the implantable electronic devices as well.

Laser-Microfabricated Polymer Multielectrodes for Intraspinal Microstimulation.

OBJECTIVE: The overall goal of this study was to design, fabricate, and characterize a new polymer-based multielectrode for the spinal cord for the application of intraspinal microstimulation (ISMS). METHODS: Three-channel multielectrodes were fabricated from modified poly(dimethylsiloxane) (PDMS) and platinum-iridium (Pt-Ir) foil using nanosecond laser microfabrication techniques. These devices were compared against traditional 50 µm diameter Pt-Ir microwire electrodes mechanically and electrochemically in bench environments, and were assessed electrochemically and functionally in vivo in a domestic pig model. RESULTS: Polymer-based multielectrodes were significantly more flexible than microwire electrodes (p < 0.05) and had greater charge storage capacities in phosphate buffered saline (p < 0.05). In a domestic pig model, multielectrodes had significantly greater charge injection limits than microwire electrodes (p < 0.05). When stimulating within the quadriceps motor pool in the spinal cord, multielectrodes generated strong knee extensor joint torques of up to 4.4 ± 0.3 Nm and were able to extend the knee by up to 26 ± 1°. However, histological analyses showed that polymer-based multielectrodes, implanted with half-needle insertion aids, produced greater acute tissue damage compared to microwire electrodes (p < 0.05). Alternative insertion methods for these flexible electrodes should be explored to reduce acute tissue damage. CONCLUSION: The PDMS-based three-channel multielectrodes demonstrated improved flexibility and charge injection capabilities over traditional microwire electrodes, and were able to produce functional responses in vivo. SIGNIFICANCE: Polymer-based multielectrodes demonstrate improved functionality over microwire electrodes while remaining more flexible than silicon multielectrode designs. These features may in the future permit polymer-based multielectrodes to implement ISMS with greater efficacy and biocompatibility compared to traditional technologies.

[Towards a positive physiological definition of the deep brain nuclei in humans]. / Hacia una definición fisiológica positiva de los núcleos cerebrales profundos en humanos.

INTRODUCTION: Using microelectrodes for recording purposes in deep brain stimulation (DBS) has proven to be very useful. Their efficiency can be improved by characterising the properties of extracellular action potentials (EAPs). PATIENTS AND METHODS: We analysed the records of nine patients who underwent surgery for epilepsy or aggressiveness under general anaesthesia. The properties of the EAPs of the centromedian, ventral intermediate, ventrocaudal and posteromedial hypothalamic nuclei of the thalamus have been determined. RESULTS: We have analysed 706 thalamic and 142 hypothalamic cells. The proportion of cell types was found to be specific to each cell nucleus. The most frequent cell type was P1P2N1 (59.5%), followed by N1P1N2 (23.1%). The first phase of the EAP is highly variable. The properties of the EAP phases of the same morphology differ greatly from one nucleus to another. CONCLUSIONS: We have shown that several deep brain nuclei have properties that are specific to the morphology of the EAPs. This will allow for improved localisation of these nuclei during DBS.

TITLE: Hacia una definición fisiológica positiva de los núcleos cerebrales profundos en humanos.Introducción. El registro con microelectrodos en la estimulación cerebral profunda (ECP) ha demostrado una gran utilidad. Es posible mejorar su eficiencia caracterizando las propiedades de los potenciales de acción extracelulares (PAE). Pacientes y métodos. Hemos analizado registros de nueve pacientes operados por epilepsia o agresividad bajo anestesia general. Se han determinado las propiedades de los PAE de los núcleos talámicos centromediano, ventral intermedio, ventrocaudal e hipotalámico posteromedial. Resultados. Hemos analizado 706 células talámicas y 142 hipotalámicas. La proporción de tipos celulares resultó específica de cada núcleo celular. El tipo celular más frecuente fue P1P2N1 (59,5%), seguido por N1P1N2 (23,1%). La primera fase del PAE es altamente variable. Las propiedades de las fases del PAE de la misma morfología difieren altamente entre núcleos. Conclusiones. Hemos demostrado que diversos núcleos cerebrales profundos tienen propiedades específicas de la morfología de los PAE. Esto permitirá una mejora en la localización de estos núcleos durante la ECP.

Repeated and On-Demand Intracellular Recordings of Cardiomyocytes Derived from Human-Induced Pluripotent Stem Cells.

Pharmaceutical compounds may have cardiotoxic properties, triggering potentially life-threatening arrhythmias. To investigate proarrhythmic effects of drugs, the patch clamp technique has been used as the gold standard for characterizing the electrophysiology of cardiomyocytes in vitro. However, the applicability of this technology for drug screening is limited, as it is complex to use and features low throughput. Recent studies have demonstrated that 3D-nanostructured electrodes enable to obtain intracellular signals from many cardiomyocytes in parallel; however, the tedious electrode fabrication and limited measurement duration still remain major issues for cardiotoxicity testing. Here, we demonstrate how porous Pt-black electrodes, arranged in high-density microelectrode arrays, can be used to record intracellular-like signals of cardiomyocytes at large scale repeatedly over an extended period of time. The developed technique, which yields highly parallelized electroporations using stimulation voltages around 1 V peak-to-peak amplitude, enabled intracellular-like recordings at high success rates without causing significant alteration in key electrophysiological features. In a proof-of-concept study, we investigated electrophysiological modulations induced by two clinically applied drugs, nifedipine and quinidine. As the obtained results were in good agreement with previously published data, we are confident that the developed technique has the potential to be routinely used in in vitro platforms for cardiotoxicity screening.

In vivo monitoring of calcium ions in rat cerebrospinal fluid using an all-solid-state acupuncture needle based potentiometric microelectrode.

Acupuncture needles are regarded as ideal materiel for the development of microelectrodes for in vivo sensing. In this work, an all-solid-state ion-selective microelectrode (ISµE) has been developed by coating a calcium ion-selective membrane on an acupuncture needle tip with a diameter of less than 80 µm, which is modified with poly(3,4-ethylenedioxythiophene)-poly(sodium 4-styrenesulfonate) as solid contact. The proposed Ca2+-ISµE shows a Nernstian response toward Ca2+ in the range from 1.0 × 10-6 to 3.1 × 10-3 M with a slope of 30.8 ± 0.9 mV/decade (R2 = 0.999), and the detection limit is 1.2 × 10-7 M. The Ca2+-ISµE has been used for in vivo monitoring of the calcium changes in rat cerebrospinal fluid (CSF) under the injury of spinal cord transection. The results demonstrate that the calcium concentration in CSF increases sharply from the normal level of 20.6 ± 1.72 µM (n = 3) to 133.2 ± 7.63 µM (n = 3) with a severe fluctuation after spinal cord damage. Thus, the proposed Ca2+-ISµE is available for in vivo monitoring of calcium ions with high temporal resolution and flexibility. The detection system can be extended to measure other ions in CSF by changing different ion-selective membranes.

Effects of Varying Pulse Width and Frequency of Wireless Stimulation in Rat Sciatic Nerve.

Peripheral nerve stimulation is a commonly used method for assisting movements after spinal cord injury, stroke, traumatic brain injury, and other types of neurological damage or dysfunction. There are many different patterns of electrical stimulation used to accomplish movement. And so, our study investigated stimulation with a wireless floating microelectrode array (WFMA) in comparison to previously reported data on functional electrical stimulation. To determine the effect on hindlimb movement, we tested a range of frequencies and pulse widths using WFMAs that were implanted in the rat sciatic nerve for 38 weeks. Frequencies between 1 and 50 Hz did not change the minimum current amplitude required to elicit movement in the hindlimb. Increasing pulse width from 57.2 to 400.4 µs decreased the minimum current required but had an associated increase in total charge applied per pulse. Overall, the WFMA provides a stable wireless peripheral nerve interface suitable for functional electrical stimulation.Clinical Relevance- This work establishes the efficacy of various stimulation parameters for controlling movement with a wireless peripheral nerve stimulator.

All-Optical and Label-Free Stimulation of Action Potentials in Neurons and Cardiomyocytes by Plasmonic Porous Metamaterials.

Optical stimulation technologies are gaining great consideration in cardiology, neuroscience studies, and drug discovery pathways by providing control over cell activity with high spatio-temporal resolution. However, this high precision requires manipulation of biological processes at genetic level concealing its development from broad scale application. Therefore, translating these technologies into tools for medical or pharmacological applications remains a challenge. Here, an all-optical nongenetic method for the modulation of electrogenic cells is introduced. It is demonstrated that plasmonic metamaterials can be used to elicit action potentials by converting near infrared laser pulses into stimulatory currents. The suggested approach allows for the stimulation of cardiomyocytes and neurons directly on commercial complementary metal-oxide semiconductor microelectrode arrays coupled with ultrafast pulsed laser, providing both stimulation and network-level recordings on the same device.

General Anesthesia vs Local Anesthesia in Microelectrode Recording-Guided Deep-Brain Stimulation for Parkinson Disease: The GALAXY Randomized Clinical Trial.

Importance: It is unknown if there is a difference in outcome in asleep vs awake deep brain stimulation (DBS) of the subthalamic nucleus for advanced Parkinson disease. Objective: To determine the difference in adverse effects concerning cognition, mood, and behavior between awake and asleep DBS favoring the asleep arm of the study. Design, Setting, and Participants: This study was a single-center prospective randomized open-label blinded end point clinical trial. A total of 187 persons with Parkinson disease were referred for DBS between May 2015 to March 2019. Analysis took place from January 2016 to January 2020. The primary outcome follow-up visit was conducted 6 months after DBS. Interventions: Bilateral subthalamic nucleus DBS was performed while the patient was asleep (under general anesthesia) in 1 study arm and awake in the other study arm. Both arms of the study used a frame-based intraoperative microelectrode recording technique to refine final target placement of the DBS lead. Main Outcomes and Measures: The primary outcome variable was the between-group difference in cognitive, mood, and behavioral adverse effects as measured by a composite score. The secondary outcomes included the Movement Disorders Society Unified Parkinson's Disease Rating Scale, the patient assessment of surgical burden and operative time. Results: A total of 110 patients were randomized to awake (local anesthesia; n = 56; mean [SD] age, 60.0 (7.4) years; 40 [71%] male) or to asleep (general anesthesia; n = 54; mean [SD] age, 61.3 [7.9] years; 38 [70%] male) DBS surgery. The 6-month follow-up visit was completed by 103 participants. The proportion of patients with adverse cognitive, mood, and behavioral effects on the composite score was 15 of 52 (29%) after awake and 11 of 51 (22%) after asleep DBS (odds ratio, 0.7 [95% CI, 0.3-1.7]). There was no difference in improvement in the off-medication Movement Disorders Society Unified Parkinson's Disease Rating Scale Motor Examination scores between groups (awake group: mean [SD], -27.3 [17.5] points; asleep group: mean [SD], -25.3 [14.3] points; mean difference, -2.0 [95% CI, -8.1 to 4.2]). Asleep surgery was experienced as less burdensome by patients and was 26 minutes shorter than awake surgery. Conclusions and Relevance: There was no difference in the primary outcome of asleep vs awake DBS. Future large randomized clinical trials should examine some of the newer asleep based DBS technologies because this study was limited to frame-based microelectrode-guided procedures. Trial Registration: trialregister.nl Identifier: NTR5809.

Transcranial alternating current stimulation entrains alpha oscillations by preferential phase synchronization of fast-spiking cortical neurons to stimulation waveform.

Computational modeling and human studies suggest that transcranial alternating current stimulation (tACS) modulates alpha oscillations by entrainment. Yet, a direct examination of how tACS interacts with neuronal spiking activity that gives rise to the alpha oscillation in the thalamo-cortical system has been lacking. Here, we demonstrate how tACS entrains endogenous alpha oscillations in head-fixed awake ferrets. We first show that endogenous alpha oscillations in the posterior parietal cortex drive the primary visual cortex and the higher-order visual thalamus. Spike-field coherence is largest for the alpha frequency band, and presumed fast-spiking inhibitory interneurons exhibit strongest coupling to this oscillation. We then apply alpha-tACS that results in a field strength comparable to what is commonly used in humans (<0.5 mV/mm). Both in these ferret experiments and in a computational model of the thalamo-cortical system, tACS entrains alpha oscillations by following the theoretically predicted Arnold tongue. Intriguingly, the fast-spiking inhibitory interneurons exhibit a stronger entrainment response to tACS in both the ferret experiments and the computational model, likely due to their stronger endogenous coupling to the alpha oscillation. Our findings demonstrate the in vivo mechanism of action for the modulation of the alpha oscillation by tACS.

On-Chip Cyclic Voltammetry Measurements Using a Compact 1024-Electrode CMOS IC.

Complementary metal-oxide-semiconductor (CMOS) microelectrode arrays integrate amplifier arrays with on-chip electrodes, offering high-throughput platforms for electrochemical sensing with high spatial and temporal resolution. Such devices have been developed for highly parallel constant voltage amperometric detection of transmitter release from multiple cells with single-vesicle resolution. Cyclic voltammetry (CV) is an electrochemical method that applies voltage waveforms, which provides additional information about electrode properties and about the nature of analytes. A 16-channel, 64-electrode-per-channel CMOS integrated circuit (IC) fabricated in a 0.5 µm CMOS process for CV is demonstrated. Each detector consists of only 11 transistors and an integration capacitor with a unit dimension of 0.0015 mm2. The device was postfabricated using Pt as the working electrode material with a shifted electrode design, which makes it possible to redefine the size and the location of working electrodes. The system incorporating cell-sized (8 µm radius) microelectrodes was validated with dopamine injection tests and CV measurements of potassium ferricyanide at a 1 V/s scanning rate. The cyclic voltammograms were in excellent agreement with theoretical predictions. The technology enables rigorous characterization of electrode performance for the application of CMOS microelectrode arrays in low-noise amperometric measurements of quantal transmitter release as well as other biosensing applications.

An iron oxide nanoworm hybrid on an interdigitated microelectrode silica surface to detect abdominal aortic aneurysms.

An abdominal aortic aneurysm (AAA) is abnormal swelling in the abdominal aorta and a prevalent life-threatening disease. This research introduces a new interdigitated microelectrode (IDME)-sensing surface modified by iron oxide nanoworms (IONWs) for detecting the AAA biomarker insulin-like growth factor-1 (IGF1). A sandwich pattern was formulated with the IGF1 aptamer and IGFBP1 (IGF binding protein-1) on the IONW-constructed IDME hybrid to identify IGF1. The surface morphology of the IONWs revealed a uniform distribution of worm-like structures (80-100 nm) as confirmed by FESEM and FETEM analyses. Further, the presence of the major elements, Fe and O, was confirmed by EDX and XPS studies. The crystal planes that appeared in the IONW reflect cubic magnetite. IONW-modified IDME attained a limit of detection for IGF1 of 1 fM (3σ) with an aptamer-IGF1-IGFBP1 sandwich. This sandwich with IGFBP1 enhanced the current level at all concentrations of IGF1 and displayed linearity in the range 1 fM to 100 pM with a determination coefficient of R2 = 0.9373 [y = 3.38221x - 4.79]. Control experiments with complementary aptamer sequences, IGF2 and IGFBP3 did not show notable signal changes, indicating the specific detection of IGF1. This IONW constructed electrode helps to achieve the detection of low amounts of IGF1 and diagnose AAA at the stage prior to rupture.

Local abnormal ventricular activity detection in scar-related VT: Microelectrode versus conventional bipolar electrode.

BACKGROUND: Conventional bipolar electrodes (CBE) may be suboptimal to detect local abnormal ventricular activities (LAVAs). Microelectrodes (ME) may improve the detection of LAVAs. This study sought to elucidate the detectability of LAVAs using ME compared with CBE in patients with scar-related ventricular tachycardia (VT). METHODS: We included consecutive patients with structural heart disease who underwent radiofrequency catheter ablation for scar-related VT using either of the following catheters equipped with ME: QDOTTM or IntellaTip MIFITM. Detection field of LAVA potentials were classified as three types: Type 1 (both CBE and ME detected LAVA), Type 2 (CBE did not detect LAVA while ME did), and Type 3 (CBE detected LAVA while ME did not). RESULTS: In 16 patients (68 ± 16 years; 14 males), 260 LAVAs electrograms (QDOT = 72; MIFI = 188) were analyzed. Type 1, type 2, and type 3 detections were 70.8% (QDOT, 69.4%; MIFI, 71.3%), 20.0% (QDOT, 23.6%; MIFI, 18.6%) and 9.2% (QDOT, 6.9%; MIFI, 10.1%), respectively. The LAVAs amplitudes detected by ME were higher than those detected by CBE in both catheters (QDOT: ME 0.79 ± 0.50 mV vs. CBE 0.41 ± 0.42 mV, p = .001; MIFI: ME 0.73 ± 0.64 mV vs. CBE 0.38 ± 0.36 mV, p < .001). CONCLUSIONS: ME allow to identify 20% of LAVAs missed by CBE. ME showed higher amplitude LAVAs than CBE. However, 9.2% of LAVAs can still be missed by ME.