Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 15.360
Filtrar
1.
Nat Commun ; 11(1): 4854, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978383

RESUMO

Chronic imaging of neuronal networks in vitro has provided fundamental insights into mechanisms underlying neuronal function. Current labeling and optical imaging methods, however, cannot be used for continuous and long-term recordings of the dynamics and evolution of neuronal networks, as fluorescent indicators can cause phototoxicity. Here, we introduce a versatile platform for label-free, comprehensive and detailed electrophysiological live-cell imaging of various neurogenic cells and tissues over extended time scales. We report on a dual-mode high-density microelectrode array, which can simultaneously record in (i) full-frame mode with 19,584 recording sites and (ii) high-signal-to-noise mode with 246 channels. We set out to demonstrate the capabilities of this platform with recordings from primary and iPSC-derived neuronal cultures and tissue preparations over several weeks, providing detailed morpho-electrical phenotypic parameters at subcellular, cellular and network level. Moreover, we develop reliable analysis tools, which drastically increase the throughput to infer axonal morphology and conduction speed.


Assuntos
Rede Nervosa/fisiologia , Neurônios/fisiologia , Imagem Óptica/métodos , Análise de Célula Única/métodos , Animais , Axônios , Encéfalo , Células Cultivadas , Células-Tronco Pluripotentes Induzidas , Camundongos , Microeletrodos , Modelos Animais , Rede Nervosa/diagnóstico por imagem , Imagem Óptica/instrumentação , Ratos , Ratos Wistar , Gravação em Vídeo
2.
PLoS One ; 15(8): e0237709, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817653

RESUMO

OBJECTIVES: In this paper, we aim to detail the setup of a high spatio-temporal resolution, electrical recording system utilising planar microelectrode arrays with simultaneous optical imaging suitable for evaluating microelectrode performance with a proposed 'performance factor' metric. METHODS: Techniques that would facilitate low noise electrical recordings were coupled with voltage sensitive dyes and neuronal activity was recorded both electrically via a customised amplification system and optically via a high speed CMOS camera. This technique was applied to characterise microelectrode recording performance of gold and poly(3,4-ethylenedioxythiophene)/polystyrene sulfonate (PEDOT/PSS) coated electrodes through traditional signal to noise (SNR) calculations as well as the proposed performance factor. RESULTS: Neuronal activity was simultaneously recorded using both electrical and optical techniques and this activity was confirmed via tetrodotoxin application to inhibit action potential firing. PEDOT/PSS outperformed gold using both measurements, however, the performance factor metric estimated a 3 fold improvement in signal transduction when compared to gold, whereas SNR estimated an 8 fold improvement when compared to gold. CONCLUSION: The design and functionality of a system to record from neurons both electrically, through microelectrode arrays, and optically via voltage sensitive dyes was successfully achieved. SIGNIFICANCE: The high spatiotemporal resolution of both electrical and optical methods will allow for an array of applications such as improved detection of subthreshold synaptic events, validation of spike sorting algorithms and a provides a robust evaluation of extracellular microelectrode performance.


Assuntos
Potenciais de Ação/fisiologia , Eletrodos Implantados , Microeletrodos , Neurônios/fisiologia , Algoritmos , Ouro/química , Humanos , Polímeros/química , Transdução de Sinais/fisiologia
3.
Nat Commun ; 11(1): 4191, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826892

RESUMO

The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying peripheral interfacing technologies. Here, we present a microscale implantable device - the nanoclip - for chronic interfacing with fine peripheral nerves in small animal models that begins to meet these constraints. We demonstrate the capability to make stable, high signal-to-noise ratio recordings of behaviorally-linked nerve activity over multi-week timescales. In addition, we show that multi-channel, current-steering-based stimulation within the confines of the small device can achieve multi-dimensional control of a small nerve. These results highlight the potential of new microscale design and fabrication techniques for realizing viable devices for long-term peripheral interfacing.


Assuntos
Microeletrodos , Nervos Periféricos/fisiologia , Impressão Tridimensional , Animais , Engenharia Biomédica , Eletrodos Implantados , Potenciais Evocados , Tentilhões/fisiologia , Masculino , Microtecnologia , Modelos Animais , Nervos Periféricos/cirurgia , Razão Sinal-Ruído
4.
PLoS One ; 15(7): e0236176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697792

RESUMO

BACKGROUND: Optimizing stimulation protocol is essential for clinical application of retinal prosthesis. Elongating stimulation pulse width (~25ms /phase) has been proposed as an effective method to improve spatial resolution of epi-retinal implants. However, it is unknown whether longer stimulus pulse width will increase the risk of damaging the retina. In addition, with the advent of next generation retinal prosthesis featuring high-density microelectrode array, it is tempting to optimizing a single set of parameters for all electrodes instead of optimizing parameters of each electrode, but this approach raised biosafety concern. We sought to study the effect of stimulus pulse width on the response of retinal ganglion cells to electrical stimulation, and evaluate if the single parameter set approach was valid based on biosafety measures. METHODS: We stimulated mouse retina using biphasic pulse waveform generated by chosen electrodes (single or a 3x3 assembly) from multiple microelectrode arrays, recorded their action potentials and performed spike sorting. We tested various stimulus intensity with two fixed pulse width: a short one for 1 millisecond per phase, and a long one for 25 milliseconds per phase. All these assays were performed on two mouse models: the wildtype C57BL/6J mice and the photoreceptor degenerated rd10 mice. The action-potential-frequency vs stimulus amplitude profiles were plotted, and three parameters were extracted: the threshold (the lowest stimulus amplitude activating RGC units), safety-limit (stimulus amplitude that attenuated the firing rate to half of the maximum response), and the stimulation amplitude range (the difference between threshold and safety limit parameters). RESULTS: In single-electrode stimulation experiment, we found that on average 85% of the recorded units showed attenuated response to extreme stimulation; among those units, an average of 51% stopped responding during stimulation ramping and failed to recover after one-hour post-stimulation, indicating extreme stimulation can damage RGC units. Twenty-five-millisecond pulse stimulation significantly reduced safety-limit and stimulation-amplitude-range parameters of recorded RGC units compared to 1ms pulse stimulation. During stimulus amplitude ramping, the maximum proportion of responsive healthy RGC units was 51% on average in 25ms pulse condition, and 76% on average in 1ms pulse condition, indicating long pulse may inflict more strain on RGCs, and a significant amount of inappropriately stimulated RGCs always exist. The contrast of these proportions could be explained by the tight correlation between the threshold and safety-limit parameter in 25ms pulse condition. These results were corroborated by those from 3x3 array stimulation experiments. CONCLUSION: Base on a biosafety measure (RGCs' evoked firing rate in response to electrical stimulation), we proposed that longer stimulation pulse width could lead to reduced retinal response and thus highlighted the importance of carefully setting the stimulation amplitude in this case. Our results also suggested that optimizing a single set of parameters for all electrodes without individual tweaking always generated a significant amount of inappropriately stimulated RGCs, especially in the long pulse stimulation condition.


Assuntos
Contenção de Riscos Biológicos/métodos , Estimulação Elétrica/métodos , Degeneração Retiniana/terapia , Células Ganglionares da Retina/fisiologia , Próteses Visuais/efeitos adversos , Potenciais de Ação/fisiologia , Animais , Estimulação Elétrica/instrumentação , Humanos , Camundongos , Microeletrodos , Fatores de Tempo
5.
J Pharmacol Sci ; 143(4): 325-329, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32487451

RESUMO

The effects of class I antiarrhythmic drugs on the automaticity of isolated guinea pig pulmonary vein myocardia were investigated using microelectrode and voltage clamp methods. All of the drugs examined reduced the maximum rate of rise of automatic action potentials. The firing frequency and rate of diastolic depolarization were decreased by aprindine, flecainide and propafenone, but not by cibenzoline, disopyramide and pilsicainide, which correlated with blockade of the sodium current component induced by ramp depolarization mimicking the diastolic depolarization. In conclusion, class I antiarrhythmic drugs which block the diastolic sodium current component inhibit the automaticity of the pulmonary vein myocardium.


Assuntos
Antiarrítmicos/farmacologia , Veias Pulmonares/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Antiarrítmicos/classificação , Cobaias , Técnicas In Vitro , Microeletrodos , Técnicas de Patch-Clamp , Veias Pulmonares/metabolismo , Sódio/metabolismo
6.
Proc Natl Acad Sci U S A ; 117(23): 13066-13077, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32461374

RESUMO

Layer 6 (L6) is the sole purveyor of corticothalamic (CT) feedback to first-order thalamus and also sends projections to higher-order thalamus, yet how it engages the full corticothalamic circuit to contribute to sensory processing in an awake animal remains unknown. We sought to elucidate the functional impact of L6CT projections from the primary visual cortex to the dorsolateral geniculate nucleus (first-order) and pulvinar (higher-order) using optogenetics and extracellular electrophysiology in awake mice. While sustained L6CT photostimulation suppresses activity in both visual thalamic nuclei in vivo, moderate-frequency (10 Hz) stimulation powerfully facilitates thalamic spiking. We show that each stimulation paradigm differentially influences the balance between monosynaptic excitatory and disynaptic inhibitory corticothalamic pathways to the dorsolateral geniculate nucleus and pulvinar, as well as the prevalence of burst versus tonic firing. Altogether, our results support a model in which L6CTs modulate first- and higher-order thalamus through parallel excitatory and inhibitory pathways that are highly dynamic and context-dependent.


Assuntos
Corpos Geniculados/fisiologia , Pulvinar/fisiologia , Córtex Visual/fisiologia , Animais , Estimulação Elétrica , Eletrodos Implantados , Feminino , Masculino , Camundongos , Microeletrodos , Optogenética , Técnicas Estereotáxicas , Vias Visuais
7.
PLoS Comput Biol ; 16(4): e1007514, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32330126

RESUMO

Learning leads to changes in population patterns of neural activity. In this study we wanted to examine how these changes in patterns of activity affect the dimensionality of neural responses and information about choices. We addressed these questions by carrying out high channel count recordings in dorsal-lateral prefrontal cortex (dlPFC; 768 electrodes) while monkeys performed a two-armed bandit reinforcement learning task. The high channel count recordings allowed us to study population coding while monkeys learned choices between actions or objects. We found that the dimensionality of neural population activity was higher across blocks in which animals learned the values of novel pairs of objects, than across blocks in which they learned the values of actions. The increase in dimensionality with learning in object blocks was related to less shared information across blocks, and therefore patterns of neural activity that were less similar, when compared to learning in action blocks. Furthermore, these differences emerged with learning, and were not a simple function of the choice of a visual image or action. Therefore, learning the values of novel objects increases the dimensionality of neural representations in dlPFC.


Assuntos
Mapeamento Encefálico , Aprendizagem/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Algoritmos , Animais , Eletrodos , Movimentos Oculares , Processamento de Imagem Assistida por Computador , Luz , Macaca , Masculino , Microeletrodos , Estimulação Luminosa , Reforço Psicológico , Recompensa , Movimentos Sacádicos
8.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(2): 271-279, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32329279

RESUMO

Spike recorded by multi-channel microelectrode array is very weak and susceptible to interference, whose noisy characteristic affects the accuracy of spike detection. Aiming at the independent white noise, correlation noise and colored noise in the process of spike detection, combining principal component analysis (PCA), wavelet analysis and adaptive time-frequency analysis, a new denoising method (PCWE) that combines PCA-wavelet (PCAW) and ensemble empirical mode decomposition is proposed. Firstly, the principal component was extracted and removed as correlation noise using PCA. Then the wavelet-threshold method was used to remove the independent white noise. Finally, EEMD was used to decompose the noise into the intrinsic modal function of each layer and remove the colored noise. The simulation results showed that PCWE can increase the signal-to-noise ratio by about 2.67 dB and decrease the standard deviation by about 0.4 µV, which apparently improved the accuracy of spike detection. The results of measured data showed that PCWE can increase the signal-to-noise ratio by about 1.33 dB and reduce the standard deviation by about 18.33 µV, which showed its good denoising performance. The results of this study suggests that PCWE can improve the reliability of spike signal and provide an accurate and effective spike denoising new method for the encoding and decoding of neural signal.


Assuntos
Algoritmos , Processamento de Sinais Assistido por Computador , Análise de Ondaletas , Microeletrodos , Análise de Componente Principal , Reprodutibilidade dos Testes , Razão Sinal-Ruído
9.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(2): 317-323, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32329285

RESUMO

As an interface between external electronic devices and internal neural nuclei, microelectrodes play an important role in many fields, such as animal robots, deep brain stimulation and neural prostheses. Aiming at the problem of high price and complicated fabrication process of microelectrode, a microelectrode twisting machine based on open source electronic prototyping platform (Arduino) and three-dimensional printing technology was proposed, and its microelectrode fabrication performance and neural stimulation performance were verified. The results show that during the fabrication of microelectrodes, the number of positive twisting turns of the electrode wire should generally be set to about 1.8 times of its length, and the number of reverse twisting rings is independent of the length, generally about 5. Moreover, compared with the traditional instrument, the device is not only inexpensive and simple to manufacture, but also has good expandability. It has a positive significance for both the personalization and popularization of microelectrode fabrication and the reduction of experimental cost.


Assuntos
Desenho de Equipamento , Microeletrodos , Impressão Tridimensional
10.
Nat Commun ; 11(1): 1878, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32313021

RESUMO

Methane is the second most important greenhouse gas after carbon dioxide and approximately 11% of the global anthropogenic methane emissions originate from rice fields. Sulfate amendment is a mitigation strategy to reduce methane emissions from rice fields because sulfate reducers and methanogens compete for the same substrates. Cable bacteria are filamentous bacteria known to increase sulfate levels via electrogenic sulfide oxidation. Here we show that one-time inoculation of rice-vegetated soil pots with cable bacteria increases the sulfate inventory 5-fold, which leads to the reduction of methane emissions by 93%, compared to control pots lacking cable bacteria. Promoting cable bacteria in rice fields by enrichment or sensible management may thus become a strategy to reduce anthropogenic methane emissions.


Assuntos
Bactérias/metabolismo , Metano/metabolismo , Oryza/metabolismo , Solo/química , Agricultura , Ciclo do Carbono , Mudança Climática , Efeito Estufa , Gases de Efeito Estufa , Concentração de Íons de Hidrogênio , Metano/análise , Microeletrodos , Microbiologia do Solo , Sulfatos/metabolismo
11.
J Vis Exp ; (156)2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32176200

RESUMO

Bioinspired soft robotic systems that mimic living organisms using engineered muscle tissue and biomaterials are revolutionizing the current biorobotics paradigm, especially in biomedical research. Recreating artificial life-like actuation dynamics is crucial for a soft-robotic system. However, the precise control and tuning of actuation behavior still represents one of the main challenges of modern soft robotic systems. This method describes a low-cost, highly scalable, and easy-to-use procedure to fabricate an electrically controllable soft robot with life-like movements that is activated and controlled by the contraction of cardiac muscle tissue on a micropatterned sting ray-like hydrogel scaffold. The use of soft photolithography methods makes it possible to successfully integrate multiple components in the soft robotic system, including micropatterned hydrogel-based scaffolds with carbon nanotubes (CNTs) embedded gelatin methacryloyl (CNT-GelMA), poly(ethylene glycol) diacrylate (PEGDA), flexible gold (Au) microelectrodes, and cardiac muscle tissue. In particular, the hydrogels alignment and micropattern are designed to mimic the muscle and cartilage structure of the sting ray. The electrically conductive CNT-GelMA hydrogel acts as a cell scaffold that improves the maturation and contraction behavior of cardiomyocytes, while the mechanically robust PEGDA hydrogel provides structural cartilage-like support to the whole soft robot. To overcome the hard and brittle nature of metal-based microelectrodes, we designed a serpentine pattern that has high flexibility and can avoid hampering the beating dynamics of cardiomyocytes. The incorporated flexible Au microelectrodes provide electrical stimulation across the soft robot, making it easier to control the contraction behavior of cardiac tissue.


Assuntos
Materiais Biocompatíveis , Microeletrodos , Miocárdio , Miócitos Cardíacos , Robótica , Animais , Biomimética , Hidrogéis , Contração Miocárdica , Nanotubos de Carbono , Polietilenoglicóis , Ratos , Ratos Sprague-Dawley , Robótica/economia , Robótica/métodos , Engenharia Tecidual/métodos , Tecidos Suporte
12.
J Vis Exp ; (156)2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32116295

RESUMO

Implantable microelectrode technologies have been widely used to elucidate neural dynamics at the microscale to gain a deeper understanding of the neural underpinnings of brain disease and injury. As electrodes are miniaturized to the scale of individual cells, a corresponding rise in the interface impedance limits the quality of recorded signals. Additionally, conventional electrode materials are stiff, resulting in a significant mechanical mismatch between the electrode and the surrounding brain tissue, which elicits an inflammatory response that eventually leads to a degradation of the device performance. To address these challenges, we have developed a process to fabricate flexible microelectrodes based on Ti3C2 MXene, a recently discovered nanomaterial that possesses remarkably high volumetric capacitance, electrical conductivity, surface functionality, and processability in aqueous dispersions. Flexible arrays of Ti3C2 MXene microelectrodes have remarkably low impedance due to the high conductivity and high specific surface area of the Ti3C2 MXene films, and they have proven to be exquisitely sensitive for recording neuronal activity. In this protocol, we describe a novel method for micropatterning Ti3C2 MXene into microelectrode arrays on flexible polymeric substrates and outline their use for in vivo micro-electrocorticography recording. This method can easily be extended to create MXene electrode arrays of arbitrary size or geometry for a range of other applications in bioelectronics and it can also be adapted for use with other conductive inks besides Ti3C2 MXene. This protocol enables simple and scalable fabrication of microelectrodes from solution-based conductive inks, and specifically allows harnessing the unique properties of hydrophilic Ti3C2 MXene to overcome many of the barriers that have long hindered the widespread adoption of carbon-based nanomaterials for high-fidelity neural microelectrodes.


Assuntos
Eletrocorticografia/instrumentação , Microeletrodos , Nanoestruturas/química , Neurônios/fisiologia , Titânio/química , Capacitância Elétrica , Condutividade Elétrica , Polímeros/química
14.
J Neurosci ; 40(12): 2430-2444, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32066581

RESUMO

Neural signals recorded at different scales contain information about environment and behavior and have been used to control Brain Machine Interfaces with varying degrees of success. However, a direct comparison of their efficacy has not been possible due to different recording setups, tasks, species, etc. To address this, we implanted customized arrays having both microelectrodes and electrocorticogram (ECoG) electrodes in the primary visual cortex of 2 female macaque monkeys, and also recorded electroencephalogram (EEG), while they viewed a variety of naturalistic images and parametric gratings. Surprisingly, ECoG had higher information and decodability than all other signals. Combining a few ECoG electrodes allowed more accurate decoding than combining a much larger number of microelectrodes. Control analyses showed that higher decoding accuracy of ECoG compared with local field potential was not because of differences in low-level visual features captured by them but instead because of larger spatial summation of the ECoG. Information was high in the 30-80 Hz range and at lower frequencies. Information in different frequencies and scales was nonredundant. These results have strong implications for Brain Machine Interface applications and for study of population representation of visual stimuli.SIGNIFICANCE STATEMENT Electrophysiological signals captured across scales by different recording electrodes are regularly used for Brain Machine Interfaces, but the information content varies due to electrode size and location. A systematic comparison of their efficiency for Brain Machine Interfaces is important but technically challenging. Here, we recorded simultaneous signals across four scales: spikes, local field potential, electrocorticogram (ECoG), and EEG, and compared their information and decoding accuracy for a large variety of naturalistic stimuli. We found that ECoGs were highly informative and outperformed other signals in information content and decoding accuracy.


Assuntos
Interfaces Cérebro-Computador , Eletrocorticografia , Córtex Visual/fisiologia , Animais , Comportamento Animal , Mapeamento Encefálico , Eletrodos Implantados , Eletroencefalografia , Fenômenos Eletrofisiológicos , Potenciais Evocados Visuais/fisiologia , Feminino , Macaca radiata , Microeletrodos , Estimulação Luminosa
15.
Sensors (Basel) ; 20(4)2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32092984

RESUMO

A smart, safe, and efficient management of water is fundamental for both developed and developing countries. Several wireless sensor networks have been proposed for real-time monitoring of drinking water quantity and quality, both in the environment and in pipelines. However, surface fouling significantly affects the long-term reliability of pipes and sensors installed in-line. To address this relevant issue, we presented a multi-parameter sensing node embedding a miniaturized slime monitor able to estimate the micrometric thickness and type of slime. The measurement of thin deposits in pipes is descriptive of water biological and chemical stability and enables early warning functions, predictive maintenance, and more efficient management processes. After the description of the sensing node, the related electronics, and the data processing strategies, we presented the results of a two-month validation in the field of a three-node pilot network. Furthermore, self-powering by means of direct energy harvesting from the water flowing through the sensing node was also demonstrated. The robustness and low cost of this solution enable its upscaling to larger monitoring networks, paving the way to water monitoring with unprecedented spatio-temporal resolution.


Assuntos
Fontes de Energia Elétrica , Monitoramento Ambiental/instrumentação , Qualidade da Água , Tecnologia sem Fio , Condutividade Elétrica , Microeletrodos , Temperatura , Interface Usuário-Computador
16.
Int J Neural Syst ; 30(2): 2050010, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32019380

RESUMO

The changes in neuronal firing activity in the primary motor cortex (M1) and supplementary motor area (SMA) were compared in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The neuronal dynamic was characterized using mathematical tools defined in different frameworks (rate, oscillations or complex patterns). Then, and for each cortical area, multivariate and discriminate analyses were further performed on these features to identify those important to differentiate between the normal and the pathological neuronal activity. Our results show a different order in the importance of the features to discriminate the pathological state in each cortical area which suggests that the M1 and the SMA exhibit dissimilarities in their neuronal alterations induced by parkinsonism. Our findings highlight the need for multiple mathematical frameworks to best characterize the pathological neuronal activity related to parkinsonism. Future translational studies are warranted to investigate the causal relationships between cortical region-specificities, dominant pathological hallmarks and symptoms.


Assuntos
Potenciais de Ação , Córtex Motor/fisiopatologia , Neurônios/fisiologia , Transtornos Parkinsonianos/fisiopatologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Potenciais de Ação/fisiologia , Animais , Ondas Encefálicas , Feminino , Modelos Lineares , Macaca fuscata , Masculino , Microeletrodos , Análise Multivariada , Dinâmica não Linear , Análise de Componente Principal , Processamento de Sinais Assistido por Computador
17.
J Vis Exp ; (155)2020 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-32009634

RESUMO

With advances in electronics and fabrication technology, intracortical microelectrodes have undergone substantial improvements enabling the production of sophisticated microelectrodes with greater resolution and expanded capabilities. The progress in fabrication technology has supported the development of biomimetic electrodes, which aim to seamlessly integrate into the brain parenchyma, reduce the neuroinflammatory response observed after electrode insertion and improve the quality and longevity of electrophysiological recordings. Here we describe a protocol to employ a biomimetic approach recently classified as nano-architecture. The use of focused ion beam lithography (FIB) was utilized in this protocol to etch specific nano-architecture features into the surface of non-functional and functional single shank intracortical microelectrodes. Etching nano-architectures into the electrode surface indicated possible improvements of biocompatibility and functionality of the implanted device. One of the benefits of using FIB is the ability to etch on manufactured devices, as opposed to during the fabrication of the device, facilitating boundless possibilities to modify numerous medical devices post-manufacturing. The protocol presented herein can be optimized for various material types, nano-architecture features, and types of devices. Augmenting the surface of implanted medical devices can improve the device performance and integration into the tissue.


Assuntos
Nanopartículas/química , Impressão , Animais , Automação , Biomarcadores/metabolismo , Encéfalo/patologia , Contagem de Células , Eletrodos Implantados , Fenômenos Eletrofisiológicos , Inflamação/patologia , Íons , Microeletrodos , Neurônios/patologia , Ratos , Silício/química
18.
Talanta ; 209: 120560, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892051

RESUMO

Antipsychotic clozapine is the most effective medication currently available for schizophrenia. However, clozapine is dramatically underutilized due to its harsh side effects that are not effectively monitored. By continuously monitoring clozapine blood levels, such as use of an implantable glucometer, which has transformed diabetes management, the treatment can be optimized and side effects will be minimized. Currently, none of the methods for clozapine detection show the ability to repeatedly measure clozapine in whole blood without pretreatment steps. Here we propose using a microelectrode modified with reduced graphene oxide-a material that was used for repeatable measurements in implantable electrochemical devices. We present the successful direct electrodeposition of reduced-graphene oxide coating onto microelectrodes. Systematic characterization of the electrodeposition technique parameters (i.e., the technique scan rate and the number of cycles) revealed their effect on the electrochemical activity and the structural properties (the film thickness and roughness) of the films. The developed reduced-graphene oxide-modified microelectrode exhibited the feasibility to detect clozapine in microliters-volume-samples of whole blood with a limit-of-detection and a sensitivity of 0.64 ±â€¯0.04 µM and 19.6 ±â€¯1.3 µA/cm2µM, respectively. Moreover, the reduced graphene oxide-modified microelectrodes exhibited high repeatability (retaining 94.6% of the electrochemical signal after 10 repeats), reproducibility (3.6% relative standard deviation), and storage stability (retaining 89% of the electrochemical signal after 4 weeks). Finally, relative recovery studies of 0.5, 1, and 2 µM clozapine concentrations resulted in 108 ±â€¯4.0%, 112 ±â€¯3.5%, and 103 ±â€¯2.2%, respectively. Future studies should investigate the microelectrode fouling mechanisms in whole blood and explore methods to overcome fouling.


Assuntos
Antipsicóticos/sangue , Clozapina/sangue , Técnicas Eletroquímicas/instrumentação , Grafite/química , Monitoramento de Medicamentos/instrumentação , Desenho de Equipamento , Humanos , Limite de Detecção , Microeletrodos , Oxirredução
19.
Sci Rep ; 10(1): 1429, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996696

RESUMO

Hybrid kinetic and kinematic intracortical brain-computer interfaces (iBCIs) have the potential to restore functional grasping and object interaction capabilities in individuals with tetraplegia. This requires an understanding of how kinetic information is represented in neural activity, and how this representation is affected by non-motor parameters such as volitional state (VoS), namely, whether one observes, imagines, or attempts an action. To this end, this work investigates how motor cortical neural activity changes when three human participants with tetraplegia observe, imagine, and attempt to produce three discrete hand grasping forces with the dominant hand. We show that force representation follows the same VoS-related trends as previously shown for directional arm movements; namely, that attempted force production recruits more neural activity compared to observed or imagined force production. Additionally, VoS-modulated neural activity to a greater extent than grasping force. Neural representation of forces was lower than expected, possibly due to compromised somatosensory pathways in individuals with tetraplegia, which have been shown to influence motor cortical activity. Nevertheless, attempted forces (but not always observed or imagined forces) could be decoded significantly above chance, thereby potentially providing relevant information towards the development of a hybrid kinetic and kinematic iBCI.


Assuntos
Córtex Motor/fisiologia , Próteses Neurais , Quadriplegia/terapia , Volição/fisiologia , Fenômenos Biomecânicos , Engenharia Biomédica , Interfaces Cérebro-Computador , Doença Crônica , Força da Mão , Humanos , Imaginação , Masculino , Microeletrodos , Pessoa de Meia-Idade , Córtex Motor/cirurgia , Recuperação de Função Fisiológica , Transmissão Sináptica
20.
J Neurosci ; 40(8): 1668-1678, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31941667

RESUMO

Understanding the neural code requires understanding how populations of neurons code information. Theoretical models predict that information may be limited by correlated noise in large neural populations. Nevertheless, analyses based on tens of neurons have failed to find evidence of saturation. Moreover, some studies have shown that noise correlations can be very small, and therefore may not affect information coding. To determine whether information-limiting correlations exist, we implanted eight Utah arrays in prefrontal cortex (PFC; area 46) of two male macaque monkeys, recording >500 neurons simultaneously. We estimated information in PFC about saccades as a function of ensemble size. Noise correlations were, on average, small (∼10-3). However, information scaled strongly sublinearly with ensemble size. After shuffling trials, destroying noise correlations, information was a linear function of ensemble size. Thus, we provide evidence for the existence of information-limiting noise correlations in large populations of PFC neurons.SIGNIFICANCE STATEMENT Recent theoretical work has shown that even small correlations can limit information if they are "differential correlations," which are difficult to measure directly. However, they can be detected through decoding analyses on recordings from a large number of neurons over a large number of trials. We have achieved both by collecting neural activity in dorsal-lateral prefrontal cortex of macaques using eight microelectrode arrays (768 electrodes), from which we were able to compute accurate information estimates. We show, for the first time, strong evidence for information-limiting correlations. Despite pairwise correlations being small (on the order of 10-3), they affect information coding in populations on the order of 100 s of neurons.


Assuntos
Modelos Neurológicos , Rede Nervosa/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Potenciais de Ação/fisiologia , Animais , Macaca mulatta , Masculino , Microeletrodos , Estimulação Luminosa , Movimentos Sacádicos/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA