Detection and classification of sensory information from acute spinal cord recordings

One avenue of research for partial restoration of function following spinal cord injury is the use of neural prostheses, an example of which is functional electrical stimulation (FES) devices for motor functions. Neural prostheses may also be useful for the extraction of sensory information directly from the nervous system. We suggest the spinal cord as a possible site for the detection of peripheral sensory information from neural activity alone. Acute multichannel extracellular recordings were used to extract neural spike activity elicited from peripheral sensations from the spinal cords of rats. To test the recording method and classification potential, eight classes of sensory events were recorded consisting of electrical stimulation of seven locations on rat forepaws, and another class of data during which no stimulus was present. A dual-stage classification scheme using principal component analysis and k-Means clustering was devised to classify the sensory events during single trials. The eight tasks were correctly identified at a mean accuracy of 96%. Thus, we have shown the methodology to detect and classify peripheral sensory information from multichannel recordings of the spinal cord. These methods may be useful, for example, in a closed-loop FES for restoration of hand grasp.     

A flexible depth probe using liquid crystal polymer

We proposed a method of making a flexible depth-type neural probe using liquid crystal polymer. Conventional depth neural probes made of metal or silicon have the limitations of a single recording site per shank or the brittleness of the silicon substrate. To avoid these drawbacks, polymer-based depth neural probes have been developed with biocompatible polymers such as polyimides or parylenes. However, those have suffered from the difficulty of inserting the probes into brain tissues due to their high flexibility, requiring mechanical reinforcements. Herein, we report the first attempt to use a flexible material, liquid crystal polymer (LCP), as a substrate for a depth-type neural probe. The LCP-based probe offers a controllable stiffness vs. flexibility and compatibility with thin-film processes in addition to its inherent characteristics such as high reliability and biocompatibility. In the present study, an LCP neural probe was fabricated to have enough stiffness to penetrate the dura mater of rodent brains without a guide tool or additional reinforcement structures. A simultaneous multichannel neural recording was successfully achieved from the somatosensory motor cortex of the rodents. Immunohistochemistry showed that the electrodes could be inserted into the desired regions in the brain.     

An implantable optrode composed of fiber and flexible thin-film electrode

An implantable optrode composed of fiber and multi-channel flexible thin-film electrode is developed. The flexible recording electrode is made from polyimide and is wrapped around the optical fiber. The front end of the fiber is tapered by wet etching. With the tapered shape, the light can leak from the sidewall of the fiber, and the tapered tip makes it easy to be implanted. The flexible electrode is attached with its recording sites aligning to the tapered part on the fiber. With this method, the fiber acts as an optical waveguide, as well as a support probe for flexible thin-film electrode. This novel device simplifies the fabrication process and decreases the size of the optrode. The device works well in vivo and the optical caused spike can be recorded with signal-to-noise ratio of 6:1.     

In vivo validation of custom-designed silicon-based microelectrode arrays for long-term neural recording and stimulation

We developed and validated silicon-based neural probes for neural stimulating and recording in long-term implantation in the brain. The probes combine the deep reactive ion etching process and mechanical shaping of their tip region, yielding a mechanically sturdy shank with a sharpened tip to reduce insertion force into the brain and spinal cord, particularly, with multiple shanks in the same array. The arrays' insertion forces have been quantified in vitro. Five consecutive chronically-implanted devices were fully functional from 3 to 18 months. The microelectrode sites were electroplated with iridium oxide, and the charge injection capacity measurements were performed both in vitro and after implantation in the adult feline brain. The functionality of the chronic array was validated by stimulating in the cochlear nucleus and recording the evoked neuronal activity in the central nucleus of the inferior colliculus. The arrays' recording quality has also been quantified in vivo with neuronal spike activity recorded up to 566 days after implantation. Histopathology evaluation of neurons and astrocytes using immunohistochemical stains indicated minimal alterations of tissue architecture after chronic implantation.     

用3D-FDTD法分析用于近场光存储的光纤探针电磁波传输特性

提高近场光存储的存储信息密度的关键主要在于掌握近场存储光纤探针的透光率、近场光斑直径尺寸以及场梯度等近场物理量。采用三维时域有限差分 (3D FDTD)法分析了可用于近场光存储的光纤探针尖的光学性质 ,对不同类型光纤的近场光场分布进行了数值计算 ,给出结果并进行比较 ,从光学性质的角度对其在近场光存储中的应用加以讨论。完全镀膜光纤尖在极近场处的光斑可获得 10nm的尺寸 ,远小于传统光纤光学聚焦的光斑尺寸大小。     

Artifact‐Free 2D Mapping of Neural Activity In Vivo through Transparent Gold Nanonetwork Array

With the rapid increase in the use of optogenetics to investigate the nervous system, there is a high demand for a neural interface that enables 2D mapping of electrophysiological neural signals with high precision during simultaneous light stimulation. Here, a gold nanonetwork (Au NN)‐based transparent neural electrocorticogram (ECoG) monitoring system is proposed as implantable neural electronics. The neural interface enables accurate 2D mapping of ECoG neural signals without any photoelectric artifact during light stimulation. By using the Au NN, not only the transmittance of the microelectrodes is increased by 81% but also a low electrochemical impedance of 33.9 kΩ at 1 kHz with improved mechanical stability is achieved. It is demonstrated that the transparent microelectrode array records multichannel in vivo neural activities with no photoelectric artifact and a high signal‐to‐noise ratio. Propagation of neural dynamics of optically driven neural activities is also clearly visualized using the 2D Au NN microelectrode array. This transparent, flexible ECoG microelectrode array is a promising candidate for next‐generation in vitro and in vivo neural interface for 2D mapping of neural dynamics.     

Customizing MRI-Compatible Multifunctional Neural Interfaces through Fiber Drawing

Fiber drawing enables scalable fabrication of multifunctional flexible fibers that integrate electrical, optical, and microfluidic modalities to record and modulate neural activity. Constraints on thermomechanical properties of materials, however, have prevented integrated drawing of metal electrodes with low-loss polymer waveguides for concurrent electrical recording and optical neuromodulation. Here, two fabrication approaches are introduced: 1) an iterative thermal drawing with a soft, low melting temperature (T_m) metal indium, and 2) a metal convergence drawing with traditionally non-drawable high T_m metal tungsten. Both approaches deliver multifunctional flexible neural interfaces with low-impedance metallic electrodes and low-loss waveguides, capable of recording optically-evoked and spontaneous neural activity in mice over several weeks. These fibers are coupled with a light-weight mechanical microdrive (1 g) that enables depth-specific interrogation of neural circuits in mice following chronic implantation. Finally, the compatibility of these fibers with magnetic resonance imaging is demonstrated and they are applied to visualize the delivery of chemical payloads through the integrated channels in real time. Together, these advances expand the domains of application of the fiber-based neural probes in neuroscience and neuroengineering.     

Multi‐Functional Probe Recording: Field‐Induced Recording and Near‐Field Optical Readout

We demonstrate a high‐speed recording based on field‐induced manipulation in combination with an optical reading of recorded bits on Au cluster films using the atomic force microscope (AFM) and the near‐field scanning optical microscope (NSOM). We reproduced 50 nm‐sized mounds by applying short electrical pulses to conducting tips in a non‐contact mode as a writing process. The recorded marks were then optically read using bent fiber probes in a transmission mode. A strong enhancement of light transmission is attributed to the local surface plasmon excitation on the protruded dots.     

Simple Near‐Field Optical Recording Using Bent Cantilever Probes

This paper describes our high‐density near‐field optical recording using bent cantilever fiber probes installed in an atomic force microscope. We conducted a near‐field reading of nano‐scale hole patterns with a 100 nm spatial resolution and a 25 µm/s scan speed; this implies a capability of a data reading density of 60 Gb/in² with a 0.25 kbps data transfer rate. In addition, we investigated re‐writable near‐field recording on photochromic diarylethene films. We successfully recorded erasable memory bits having a minimum width of 600 nm in a writing time as short as 30 ms. We found that using a cantilever probe simplifies the setup and operation of the near‐field optical recording system and may offer multifunctional recording capabilities.     

应用于光遗传的双光通道32记录点植入式光电极

光遗传(Optogenetics)结合光学和遗传学手段,可以精确地控制特定神经元的活动,为神经科学的研究提供了强有力的手段.光电极在光遗传研究中起着关键的作用,它可以将光导入到动物体内,并通过电极记录神经元在光调控下的活动.为了减小体积、增加功能,依托高密度集成硅微电极和裸光纤,设计并制备了一种植入部分横截面尺寸不超过0.1 mm2、包含2个平行的给光通道和32个记录点的光电极器件.与传统的单光通道电极相比,两个通道可以更灵活地配置不同的激发波长,对不同位点的神经元同时进行激活或抑制.32通道的硅电极与传统的金属丝电极相比,集成度更高,能够以更高的空间分辨率记录神经元在激发前后的活动情况.     

Ultralow Impedance Graphene Microelectrodes with High Optical Transparency for Simultaneous Deep Two‐Photon Imaging in Transgenic Mice

The last decades have witnessed substantial progress in optical technologies revolutionizing our ability to record and manipulate neural activity in genetically modified animal models. Meanwhile, human studies mostly rely on electrophysiological recordings of cortical potentials, which cannot be inferred from optical recordings, leading to a gap between our understanding of dynamics of microscale populations and brain‐scale neural activity. By enabling concurrent integration of electrical and optical modalities, transparent graphene microelectrodes can close this gap. However, the high impedance of graphene constitutes a big challenge toward the widespread use of this technology. Here, it is experimentally demonstrated that this high impedance of graphene microelectrodes is fundamentally limited by quantum capacitance. This quantum capacitance limit is overcome by creating a parallel conduction path using platinum nanoparticles. A 100 times reduction in graphene electrode impedance is achieved, while maintaining the high optical transparency crucial for deep two‐photon microscopy. Using a transgenic mouse model, simultaneous electrical recording of cortical activity with high fidelity is demonstrated while imaging calcium signals at various cortical depths right beneath the transparent microelectrodes. Multimodal analysis of Ca²⁺ spikes and cortical surface potentials offers unique opportunities to bridge our understanding of cellular dynamics and brain‐scale neural activity.     

近红外脉冲刺激神经的初步实验研究

近红外光刺激因其非侵入性、高空间分辨率等优势,成为近年来正在研究的一项新的神经刺激技术。目的:探讨808nm近红外脉冲光刺激神经组织的有效性和安全性。方法:本文中搭建了808nm光刺激实验平台,主要包括808nm激光器、恒流源以及基于MC9S12XE的控制电路,根据实验要求对激光器脉冲输出性能进行了测试;经光纤耦合后,用频率2Hz,脉宽100至1000us脉冲光刺激大鼠初级运动皮层,记录并分析皮层神经元响应。结果:在控制电路调制下激光器脉冲近红外光输出参数稳定;随着脉冲光能量的增加,初级运动皮层神经元spike发放率增加,且在0.2894至2.8939J/cm2阈值范围内光刺激未对神经细胞造成可见性热损伤。结论:本文中实现了808nm激光器脉冲光控制,实验结果初步证实了短波近红外脉冲光刺激中枢神经系统的有效性和安全性。     

Band-tunable and multiplexed integrated circuits for simultaneous recording and stimulation with microelectrode arrays

Two thin-film microelectrode arrays with integrated circuitry have been developed for extracellular neural recording in behaving animals. An eight-site probe for simultaneous neural recording and stimulation has been designed that includes on-chip amplifiers that can be individually bypassed, allowing direct access to the iridium sites for electrical stimulation. The on-probe amplifiers have a gain of 38.9 dB, an upper-cutoff frequency of 9.9 kHz, and an input-referred noise of 9.2 microV rms integrated from 100 Hz to 10 kHz. The low-frequency cutoff of the amplifier is tunable to allow the recording of field potentials and minimize stimulus artifact. The amplifier consumes 68 microW from +/- 1.5 V supplies and occupies 0.177 mm2 in 3 microm features. In vivo recordings have shown that the preamplifiers can record single-unit activity 1 ms after the onset of stimulation on sites as close as 20 microm to the stimulating electrode. A second neural recording array has been developed which multiplexes 32 neural signals onto four output data leads. Providing gain on this array eliminates the need for bulky headmounted circuitry and reduces motion artifacts. The time-division multiplexing circuitry has crosstalk between consecutive channels of less than 6% at a sample rate of 20 kHz per channel. Amplified, time-division-multiplexed multichannel neural recording allows the large-scale recording of neuronal activity in freely behaving small animals with minimum number of interconnect leads.     

Estimation of fiber diameters in the spinal dorsal columns fromclinical data

Lack of human morphometric data regarding the largest nerve fibers in the dorsal columns (DCs) of the spinal cord has lead to the estimation of the diameters of these fibers from clinical data retrieved from patients with a new spinal cord stimulation (SCS) system. These patients indicated the perception threshold of stimulation induced paresthesia in various body segments, while the stimulation amplitude was increased. The fiber diameters were calculated with a computer model, developed to calculate the effects of SCS on spinal nerve fibers. This computer model consists of two parts: (1) a three-dimensional (3-D) volume conductor model of a spinal cord segment in which the potential distribution due to electrical stimulation is calculated and (2) an electrical equivalent cable model of myelinated nerve fiber, which uses the calculated potential field to determine the threshold stimulus needed for activation. It is shown that the largest fibers in the medial DCs are significantly smaller than the largest fibers in the lateral parts. This finding is in accordance with the fiber distribution in cat, derived from the corresponding propagation velocities. Moreover, it is shown that the mediolateral increase in fiber diameter is mainly confined to the lateral parts of the DCs. Implementation of this mediolateral fiber diameter distribution of the DCs in the computer model enables the prediction of the recruitment order of dermatomal paresthesias following increasing electrical stimulation amplitude     

Graphene Heterostructure Integrated Optical Fiber Bragg Grating for Light Motion Tracking and Ultrabroadband Photodetection from 400 nm to 10.768 µm

Integrated photonics and optoelectronics devices based on graphene and related 2D materials are at the core of the future industrial revolution, facilitating compact and flexible nanophotonic devices. Tracking and detecting the motion of broadband light in millimeter to nanometer scale is an unfold science which has not been fully explored. In this work, tracking and detecting the motion of light (millimeter precision) is first demonstrated by integrating graphene with an optical fiber Bragg grating device (graphene‐FBG). When the incident light moves toward and away from the graphene‐FBG device, the Bragg wavelength red‐shifts and blue‐shifts, indicating its light motion tracking ability. Such light tracking capability can be further extended to an ultrabroad wavelength range as all‐optical photodetectors show the robust response from 400 nm to 10.768 µm with a linear optical response. Interestingly, it is found that graphene‐Bi₂Te₃ heterostructure on FBG shows 87% higher photoresponse than graphene‐FBG at both visible and telecom wavelengths, due to stronger phonon‐electron coupling and photo‐thermal conversion in the heterostructure. The device also shows superior stability even after 100 d. This work may open up amazing integrated nanophotonics applications such as astrophysics, optical communication, optical computing, optical logic gating, spectroscopy, and laser biology.     

神经网络在ATM光纤高速智能管理网中的应用(连载)

首先扼要地讨论了光纤通信领域在新世纪面临的严重任务 ,接着详细地介绍了神经网络的基本概念 ,重点论述了神经网络在 ATM光纤高速智能管理网中的应用。最后指出 ,神经网络应用于通信领域可以实现快捷、灵活、自适应性和智能化实时管理 ,在某些方面可以解决即使数学计算机也会感到棘手的难题。     

Microcomputer-based portable long-term spasticity recording system

A device for long-term monitoring of muscle activity (EMG) with surface electrodes and method of its application are described in this paper. This device is called a microcomputer two-channel EMG monitor. The device can be used for up to 24 h monitoring of EMG activity, followed by data transfer to a host computer for signal analysis. This device records amplified, rectified, and integrated EMG activity. Shorter recording time allows shorter sampling periods suitable for different other EMG analysis. Recording of spontaneous EMG in complete spinal cord injured subjects was the original reason for the design of the long-term monitor. These recordings were used for estimation of spasticity in complete spinal cord patients.     

组合锥型光纤SERS探针的理论设计与优化

对组合锥型光纤表面增强拉曼（SERS）探针的结构参数进行了设计与优化。通过建立描述消逝波激发组合锥光纤探针表面纳米颗粒的激发光衰减系数模型,结合激发光经渐变锥段的全反射传输、探针平直段与激发光纤间的模式匹配原理,给出了组合锥型光纤SERS探针的结构参数设计与优化方法。利用该设计与优化方法,在给定的光纤和纳米颗粒结构以及周围环境和激发光功率下,进行了光纤SERS探针结构参数的模拟设计。     

Multifunctional Flexible Biointerfaces for Simultaneous Colocalized Optophysiology and Electrophysiology

Recent developments in optophysiology techniques such as optogenetics have revolutionized the ability to actuate cell activity. Further combining optophysiology and electrophysiology will integrate the advantages from both optical and electrical modalities and yield enabling technologies that allow simultaneous monitoring of cellular activity in response to modulation, which are crucial for biomedical applications. However, multifunctional devices that can deliver optical stimuli to regions beneath the electrodes and perform simultaneous sensing remain largely unexplored. Existing transparent microelectrode technologies depend on external bulk optical instruments for optical interventions. Here, innovative monolithic integrated multifunctional microsystems are demonstrated by applying transparent nanogrid electrodes onto microscale light sources to permit simultaneous electrophysiology and optical modulation at the same anatomical site. The nanogrid electrodes have transmittances > 70% with a low normalized impedance of 5.9 Ω cm². Additional features of the devices include superior mechanical flexibility, minimized light‐induced electrical artifacts, and excellent biocompatibility. Ex vivo experiments demonstrate that the multifunctional devices can record abnormal heart rhythm in transgenic mouse hearts and simultaneously restore the sinus rhythm via optogenetic pacing. This work provides a versatile approach for constructing multifunctional colocalized biointerfaces containing crosstalk‐free optical and electrical modalities with expanded opportunities in both fundamental and applied biomedical research.     

Soft,Flexible Freestanding Neural Stimulation and Recording Electrodes Fabricated from Reduced Graphene Oxide

There is an urgent need for conductive neural interfacing materials that exhibit mechanically compliant properties, while also retaining high strength and durability under physiological conditions. Currently, implantable electrode systems designed to stimulate and record neural activity are composed of rigid materials such as crystalline silicon and noble metals. While these materials are strong and chemically stable, their intrinsic stiffness and density induce glial scarring and eventual loss of electrode function in vivo. Conductive composites, such as polymers and hydrogels, have excellent electrochemical and mechanical properties, but are electrodeposited onto rigid and dense metallic substrates. In the work described here, strong and conductive microfibers (40–50 μm diameter) wet‐spun from liquid crystalline dispersions of graphene oxide are fabricated into freestanding neural stimulation electrodes. The fibers are insulated with parylene‐C and laser‐treated, forming “brush” electrodes with diameters over 3.5 times that of the fiber shank. The fabrication method is fast, repeatable, and scalable for high‐density 3D array structures and does not require additional welding or attachment of larger electrodes to wires. The electrodes are characterized electrochemically and used to stimulate live retina in vitro. Additionally, the electrodes are coated in a water‐soluble sugar microneedle for implantation into, and subsequent recording from, visual cortex.