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Bio-inspired hybrid microelectrodes: a hybrid solution to improve long-term performance of chronic intracortical implants. 仿生混合微电极:一种改善慢性皮质内植入物长期性能的混合解决方案。
Pub Date : 2014-04-10 eCollection Date: 2014-01-01 DOI: 10.3389/fneng.2014.00007
Sara De Faveri, Emma Maggiolini, Ermanno Miele, Francesco De Angelis, Fabrizia Cesca, Fabio Benfenati, Luciano Fadiga

The use of implants that allow chronic electrical stimulation and recording in the brain of human patients is currently limited by a series of events that cause the deterioration over time of both the electrode surface and the surrounding tissue. The main reason of failure is the tissue inflammatory reaction that eventually causes neuronal loss and glial encapsulation, resulting in a progressive increase of the electrode-electrolyte impedance. Here, we describe a new method to create bio-inspired electrodes to mimic the mechanical properties and biological composition of the host tissue. This combination has a great potential to increase the implant lifetime by reducing tissue reaction and improving electrical coupling. Our method implies coating the electrode with reprogrammed neural or glial cells encapsulated within a hydrogel layer. We chose fibrin as a hydrogel and primary hippocampal neurons or astrocytes from rat brain as cellular layer. We demonstrate that fibrin coating is highly biocompatible, forms uniform coatings of controllable thickness, does not alter the electrochemical properties of the microelectrode and allows good quality recordings. Moreover, it reduces the amount of host reactive astrocytes - over time - compared to a bare wire and is fully reabsorbed by the surrounding tissue within 7 days after implantation, avoiding the common problem of hydrogels swelling. Both astrocytes and neurons could be successfully grown onto the electrode surface within the fibrin hydrogel without altering the electrochemical properties of the microelectrode. This bio-hybrid device has therefore a good potential to improve the electrical integration at the neuron-electrode interface and support the long-term success of neural prostheses.

目前,允许在人类患者的大脑中进行慢性电刺激和记录的植入物的使用受到一系列事件的限制,这些事件会导致电极表面和周围组织随着时间的推移而恶化。失败的主要原因是组织炎症反应,最终导致神经元丢失和胶质包封,导致电极-电解质阻抗进行性增加。在这里,我们描述了一种创造仿生电极的新方法,以模仿宿主组织的机械特性和生物组成。通过减少组织反应和改善电耦合,这种组合有很大的潜力来增加植入物的使用寿命。我们的方法是在电极上包裹一层水凝胶层内的重编程神经细胞或胶质细胞。我们选择纤维蛋白作为水凝胶,以大鼠脑原代海马神经元或星形胶质细胞作为细胞层。我们证明纤维蛋白涂层具有高度的生物相容性,形成厚度可控的均匀涂层,不改变微电极的电化学特性,并允许高质量的记录。此外,与裸丝相比,随着时间的推移,它减少了宿主反应性星形胶质细胞的数量,并且在植入后7天内被周围组织完全重新吸收,避免了水凝胶肿胀的常见问题。星形胶质细胞和神经元都可以在纤维蛋白水凝胶内成功生长在电极表面,而不会改变微电极的电化学性质。因此,这种生物混合装置在改善神经元-电极界面的电集成和支持神经假体的长期成功方面具有良好的潜力。
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引用次数: 40
A new dynamic tactile display for reconfigurable braille: implementation and tests. 一种新的可重构盲文动态触觉显示:实现与测试。
Pub Date : 2014-04-08 eCollection Date: 2014-01-01 DOI: 10.3389/fneng.2014.00006
Paolo Motto Ros, Vittorio Dante, Luca Mesin, Erminio Petetti, Paolo Del Giudice, Eros Pasero

Different tactile interfaces have been proposed to represent either text (braille) or, in a few cases, tactile large-area screens as replacements for visual displays. None of the implementations so far can be customized to match users' preferences, perceptual differences and skills. Optimal choices in these respects are still debated; we approach a solution by designing a flexible device allowing the user to choose key parameters of tactile transduction. We present here a new dynamic tactile display, a 8 × 8 matrix of plastic pins based on well-established and reliable piezoelectric technology to offer high resolution (pin gap 0.7mm) as well as tunable strength of the pins displacement, and refresh rate up to 50s(-1). It can reproduce arbitrary patterns, allowing it to serve the dual purpose of providing, depending on contingent user needs, tactile rendering of non-character information, and reconfigurable braille rendering. Given the relevance of the latter functionality for the expected average user, we considered testing braille encoding by volunteers a benchmark of primary importance. Tests were performed to assess the acceptance and usability with minimal training, and to check whether the offered flexibility was indeed perceived by the subject as an added value compared to conventional braille devices. Different mappings between braille dots and actual tactile pins were implemented to match user needs. Performances of eight experienced braille readers were defined as the fraction of correct identifications of rendered content. Different information contents were tested (median performance on random strings, words, sentences identification was about 75%, 85%, 98%, respectively, with a significant increase, p < 0.01), obtaining statistically significant improvements in performance during the tests (p < 0.05). Experimental results, together with qualitative ratings provided by the subjects, show a good acceptance and the effectiveness of the proposed solution.

已经提出了不同的触觉界面来表示文本(盲文),或者在少数情况下,触觉大面积屏幕作为视觉显示的替代品。到目前为止,没有一种实现可以根据用户的偏好、感知差异和技能进行定制。在这些方面的最佳选择仍然存在争议;我们通过设计一个灵活的设备来解决这个问题,允许用户选择触觉转导的关键参数。我们在这里提出了一种新的动态触觉显示器,一种基于成熟可靠的压电技术的8 × 8塑料引脚矩阵,可提供高分辨率(引脚间隙0.7mm)以及引脚位移强度可调,刷新率高达50(-1)。它可以复制任意模式,允许它服务于双重目的,根据偶然的用户需求,提供非字符信息的触觉呈现和可重构的盲文呈现。考虑到后一种功能与预期的普通用户的相关性,我们认为由志愿者测试盲文编码是最重要的基准。进行测试是为了在最少的训练下评估接受度和可用性,并检查所提供的灵活性是否确实被受试者视为与传统盲文设备相比的附加价值。盲点和实际触觉针之间的不同映射实现以满足用户需求。八个有经验的盲文读者的表现被定义为正确识别呈现内容的分数。对不同的信息内容进行测试(随机字符串、单词、句子识别的中位数分别约为75%、85%、98%,均有显著提高,p < 0.01),测试期间的性能提高具有统计学意义(p < 0.05)。实验结果以及受试者提供的定性评分表明,所提出的解决方案具有良好的可接受性和有效性。
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引用次数: 19
Decoding repetitive finger movements with brain activity acquired via non-invasive electroencephalography. 通过无创脑电图获得的大脑活动解码重复性手指运动。
Pub Date : 2014-03-13 eCollection Date: 2014-01-01 DOI: 10.3389/fneng.2014.00003
Andrew Y Paek, Harshavardhan A Agashe, José L Contreras-Vidal

We investigated how well repetitive finger tapping movements can be decoded from scalp electroencephalography (EEG) signals. A linear decoder with memory was used to infer continuous index finger angular velocities from the low-pass filtered fluctuations of the amplitude of a plurality of EEG signals distributed across the scalp. To evaluate the accuracy of the decoder, the Pearson's correlation coefficient (r) between the observed and predicted trajectories was calculated in a 10-fold cross-validation scheme. We also assessed attempts to decode finger kinematics from EEG data that was cleaned with independent component analysis (ICA), EEG data from peripheral sensors, and EEG data from rest periods. A genetic algorithm (GA) was used to select combinations of EEG channels that maximized decoding accuracies. Our results (lower quartile r = 0.18, median r = 0.36, upper quartile r = 0.50) show that delta-band EEG signals contain useful information that can be used to infer finger kinematics. Further, the highest decoding accuracies were characterized by highly correlated delta band EEG activity mostly localized to the contralateral central areas of the scalp. Spectral analysis of EEG also showed bilateral alpha band (8-13 Hz) event related desynchronizations (ERDs) and contralateral beta band (20-30 Hz) event related synchronizations (ERSs) localized over central scalp areas. Overall, this study demonstrates the feasibility of decoding finger kinematics from scalp EEG signals.

我们研究了如何很好地从头皮脑电图(EEG)信号中解码重复性手指敲击动作。利用具有记忆功能的线性解码器,从分布在头皮上的多个EEG信号的幅值的低通滤波波动中推断出连续的食指角速度。为了评估解码器的准确性,在10倍交叉验证方案中计算了观察轨迹和预测轨迹之间的Pearson相关系数(r)。我们还评估了通过独立分量分析(ICA)、外围传感器的EEG数据和休息时段的EEG数据来解码手指运动的尝试。采用遗传算法选择解码精度最高的脑电信号通道组合。我们的结果(下四分位数r = 0.18,中位数r = 0.36,上四分位数r = 0.50)表明,delta波段脑电图信号包含有用的信息,可用于推断手指的运动学。此外,解码精度最高的特征是高度相关的δ波段脑电图活动主要定位于头皮的对侧中央区域。脑电图频谱分析也显示双侧α带(8-13 Hz)事件相关非同步(ERDs)和对侧β带(20-30 Hz)事件相关同步(ERSs)定位于头皮中央区域。总之,本研究证明了从头皮脑电信号中解码手指运动的可行性。
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引用次数: 60
Improved selectivity from a wavelength addressable device for wireless stimulation of neural tissue. 一种波长可寻址装置对神经组织无线刺激的选择性改进。
Pub Date : 2014-02-18 eCollection Date: 2014-01-01 DOI: 10.3389/fneng.2014.00005
Elif Ç Seymour, David S Freedman, Mutlu Gökkavas, Ekmel Ozbay, Mesut Sahin, M Selim Unlü

Electrical neural stimulation with micro electrodes is a promising technique for restoring lost functions in the central nervous system as a result of injury or disease. One of the problems related to current neural stimulators is the tissue response due to the connecting wires and the presence of a rigid electrode inside soft neural tissue. We have developed a novel, optically activated, microscale photovoltaic neurostimulator based on a custom layered compound semiconductor heterostructure that is both wireless and has a comparatively small volume (<0.01 mm(3)). Optical activation provides a wireless means of energy transfer to the neurostimulator, eliminating wires and the associated complications. This neurostimulator was shown to evoke action potentials and a functional motor response in the rat spinal cord. In this work, we extend our design to include wavelength selectivity and thus allowing independent activation of devices. As a proof of concept, we fabricated two different microscale devices with different spectral responsivities in the near-infrared region. We assessed the improved addressability of individual devices via wavelength selectivity as compared to spatial selectivity alone through on-bench optical measurements of the devices in combination with an in vivo light intensity profile in the rat cortex obtained in a previous study. We show that wavelength selectivity improves the individual addressability of the floating stimulators, thus increasing the number of devices that can be implanted in close proximity to each other.

微电极神经电刺激是一种很有前途的技术,用于恢复中枢神经系统因损伤或疾病而丧失的功能。与当前神经刺激器相关的问题之一是由于连接导线和软神经组织内刚性电极的存在而引起的组织反应。我们已经开发了一种新颖的、光激活的、基于定制层状化合物半导体异质结构的微尺度光伏神经刺激器,它是无线的,并且体积相对较小(
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引用次数: 18
When "I" becomes "We": ethical implications of emerging brain-to-brain interfacing technologies. 当“我”变成“我们”:新兴脑对脑接口技术的伦理含义。
Pub Date : 2014-02-12 eCollection Date: 2014-01-01 DOI: 10.3389/fneng.2014.00004
John B Trimper, Paul Root Wolpe, Karen S Rommelfanger
The idea of creating a direct connection between a human brain and a computer has a long history in science fiction. The development of brain computer interfaces (BCI), technologies permitting direct communication between a user's brain and an external device, began to become a reality in the 1970s (Vidal, 1973), and have since captured the attention of scientists and the public alike. Initially conceptualized for military use—the initial work was funded by the National Science Foundation and the Defense Advanced Research Projects Agency (DARPA)—more recently BCIs have shown promise for therapeutic uses, providing hope for restorative and even enhanced human capacities. Utilizing both invasive and non-invasive technologies, scientists are now capable of recording and translating activity from populations of neurons to operate external devices (e.g., O'Doherty et al., 2011). In early 2013, the technology took a leap forward as researchers replaced the external computer connection with a second embodied brain, dubbing the approach “brain-to-brain” interfacing (BTBI). The direct transfer of information between two brains raises new and important ethical issues. Below, we summarize the first two landmark studies in BTBI research, and then discuss ethical concerns relevant to BTBI as they are applied in clinical, research, and non-therapeutic domains.
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引用次数: 45
Abiotic-biotic characterization of Pt/Ir microelectrode arrays in chronic implants. 慢性植入物中Pt/Ir微电极阵列的非生物-生物表征。
Pub Date : 2014-02-04 eCollection Date: 2014-01-01 DOI: 10.3389/fneng.2014.00002
Abhishek Prasad, Qing-Shan Xue, Robert Dieme, Viswanath Sankar, Roxanne C Mayrand, Toshikazu Nishida, Wolfgang J Streit, Justin C Sanchez

Pt/Ir electrodes have been extensively used in neurophysiology research in recent years as they provide a more inert recording surface as compared to tungsten or stainless steel. While floating microelectrode arrays (FMA) consisting of Pt/Ir electrodes are an option for neuroprosthetic applications, long-term in vivo functional performance characterization of these FMAs is lacking. In this study, we have performed comprehensive abiotic-biotic characterization of Pt/Ir arrays in 12 rats with implant periods ranging from 1 week up to 6 months. Each of the FMAs consisted of 16-channel, 1.5 mm long, and 75 μm diameter microwires with tapered tips that were implanted into the somatosensory cortex. Abiotic characterization included (1) pre-implant and post-explant scanning electron microscopy (SEM) to study recording site changes, insulation delamination and cracking, and (2) chronic in vivo electrode impedance spectroscopy. Biotic characterization included study of microglial responses using a panel of antibodies, such as Iba1, ED1, and anti-ferritin, the latter being indicative of blood-brain barrier (BBB) disruption. Significant structural variation was observed pre-implantation among the arrays in the form of irregular insulation, cracks in insulation/recording surface, and insulation delamination. We observed delamination and cracking of insulation in almost all electrodes post-implantation. These changes altered the electrochemical surface area of the electrodes and resulted in declining impedance over the long-term due to formation of electrical leakage pathways. In general, the decline in impedance corresponded with poor electrode functional performance, which was quantified via electrode yield. Our abiotic results suggest that manufacturing variability and insulation material as an important factor contributing to electrode failure. Biotic results show that electrode performance was not correlated with microglial activation (neuroinflammation) as we were able to observe poor performance in the absence of neuroinflammation, as well as good performance in the presence of neuroinflammation. One biotic change that correlated well with poor electrode performance was intraparenchymal bleeding, which was evident macroscopically in some rats and presented microscopically by intense ferritin immunoreactivity in microglia/macrophages. Thus, we currently consider intraparenchymal bleeding, suboptimal electrode fabrication, and insulation delamination as the major factors contributing toward electrode failure.

近年来,Pt/Ir电极在神经生理学研究中得到了广泛的应用,因为与钨或不锈钢相比,它们提供了一个更惰性的记录表面。虽然由Pt/Ir电极组成的浮动微电极阵列(FMA)是神经假肢应用的一种选择,但缺乏这些FMA的长期体内功能性能表征。在这项研究中,我们对12只大鼠的Pt/Ir阵列进行了全面的非生物-生物表征,植入期从1周到6个月不等。每个fma由16通道,1.5 mm长,直径75 μm的尖端锥形微线组成,植入体感觉皮层。非生物特性包括(1)植入前和植入后扫描电子显微镜(SEM)研究记录位点变化,绝缘分层和开裂;(2)慢性体内电极阻抗谱。生物特性包括使用一组抗体(如Iba1、ED1和抗铁蛋白)研究小胶质细胞反应,后者指示血脑屏障(BBB)破坏。在植入前,阵列之间的结构发生了显著的变化,表现为不规则的绝缘、绝缘/记录表面的裂缝和绝缘分层。我们观察到几乎所有电极植入后的分层和绝缘开裂。这些变化改变了电极的电化学表面积,由于漏电通路的形成,导致阻抗长期下降。一般来说,阻抗下降与电极功能性能差相对应,这可以通过电极产率来量化。我们的非生物结果表明,制造变异性和绝缘材料是导致电极失效的重要因素。生物实验结果表明,电极性能与小胶质细胞激活(神经炎症)无关,因为我们能够观察到,在没有神经炎症的情况下,电极表现不佳,而在神经炎症存在的情况下,电极表现良好。与电极性能差密切相关的一种生物变化是肝实质内出血,这在一些大鼠的宏观上很明显,在显微镜下则表现为小胶质细胞/巨噬细胞中强烈的铁蛋白免疫反应。因此,我们目前认为肺实质内出血、不理想的电极制作和绝缘分层是导致电极失效的主要因素。
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引用次数: 119
Low-latency multi-threaded processing of neuronal signals for brain-computer interfaces. 脑机接口神经元信号的低延迟多线程处理。
Pub Date : 2014-01-28 eCollection Date: 2014-01-01 DOI: 10.3389/fneng.2014.00001
Jörg Fischer, Tomislav Milekovic, Gerhard Schneider, Carsten Mehring

Brain-computer interfaces (BCIs) require demanding numerical computations to transfer brain signals into control signals driving an external actuator. Increasing the computational performance of the BCI algorithms carrying out these calculations enables faster reaction to user inputs and allows using more demanding decoding algorithms. Here we introduce a modular and extensible software architecture with a multi-threaded signal processing pipeline suitable for BCI applications. The computational load and latency (the time that the system needs to react to user input) are measured for different pipeline implementations in typical BCI applications with realistic parameter settings. We show that BCIs can benefit substantially from the proposed parallelization: firstly, by reducing the latency and secondly, by increasing the amount of recording channels and signal features that can be used for decoding beyond the amount which can be handled by a single thread. The proposed software architecture provides a simple, yet flexible solution for BCI applications.

脑机接口(bci)需要严格的数值计算来将脑信号转换为驱动外部执行器的控制信号。提高执行这些计算的BCI算法的计算性能可以更快地对用户输入作出反应,并允许使用更苛刻的解码算法。本文介绍了一种适合BCI应用的具有多线程信号处理管道的模块化可扩展软件体系结构。在典型的BCI应用程序中,计算负载和延迟(系统对用户输入作出反应所需的时间)在具有实际参数设置的不同管道实现中被测量。我们表明,bci可以从提议的并行化中受益匪浅:首先,通过减少延迟,其次,通过增加可用于解码的记录通道和信号特征的数量,这些数量超出了单线程可以处理的数量。所提出的软件体系结构为BCI应用程序提供了一个简单而灵活的解决方案。
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引用次数: 62
The sinusoidal probe: a new approach to improve electrode longevity. 正弦探头:提高电极寿命的新方法。
Pub Date : 2014-01-01 DOI: 10.3389/fneng.2014.00010
Harbaljit S Sohal, Andrew Jackson, Richard Jackson, Gavin J Clowry, Konstantin Vassilevski, Anthony O'Neill, Stuart N Baker

Micromotion between the brain and implanted electrodes is a major contributor to the failure of invasive brain-machine interfaces. Movements of the electrode tip cause recording instabilities while spike amplitudes decline over the weeks/months post-implantation due to glial cell activation caused by sustained mechanical trauma. We have designed a sinusoidal probe in order to reduce movement of the recording tip relative to the surrounding neural tissue. The probe was microfabricated from flexible materials and incorporated a sinusoidal shaft to minimize tethering forces and a 3D spheroid tip to anchor the recording site within the brain. Compared to standard microwire electrodes, the signal-to-noise ratio and local field potential power of sinusoidal probe recordings from rabbits was more stable across recording periods up to 678 days. Histological quantification of microglia and astrocytes showed reduced neuronal tissue damage especially for the tip region between 6 and 24 months post-implantation. We suggest that the micromotion-reducing measures incorporated into our design, at least partially, decreased the magnitude of gliosis, resulting in enhanced longevity of recording.

大脑和植入电极之间的微运动是侵入性脑机接口失效的主要原因。电极尖端的运动导致记录不稳定,而在植入后的几周/几个月内,由于持续的机械损伤引起的神经胶质细胞激活,峰值振幅下降。我们设计了一个正弦探头,以减少记录尖端相对于周围神经组织的运动。该探针由柔性材料制成,并包含一个正弦轴,以最大限度地减少系绳力,以及一个3D球形尖端,将记录位置固定在大脑内。与标准微丝电极相比,在长达678天的记录期内,家兔正弦探头记录的信噪比和局部场电位更加稳定。小胶质细胞和星形胶质细胞的组织学定量显示,在植入后6至24个月,神经组织损伤减少,尤其是尖端区域。我们建议将微动减少措施纳入我们的设计中,至少部分地减少了胶质瘤的大小,从而延长了记录的寿命。
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引用次数: 95
Closing the loop in neuroprosthetics 闭合神经修复术的循环
Pub Date : 2014-01-01 DOI: 10.3389/CONF.FNENG.2014.11.00007
M. Silvestro
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引用次数: 0
Regenerative neural interfaces for neuroprosthetic applications 神经义肢应用的再生神经接口
Pub Date : 2014-01-01 DOI: 10.3389/CONF.FNENG.2014.11.00003
Navarro-Sune Xavier, Del Valle Jaume
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引用次数: 4
期刊
Frontiers in neuroengineering
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