Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.

脑电可穿戴无线射频发射芯片系统的研究

针对脑电EEG (electroencephalograph)传感网络近距离无线传输与可穿戴应用的需要,给出了一款无线射频电路控制系统:集成了模拟电路(8通道低噪声脑电放大器与中速SAR-ADC模数转换)、信道编码EEG-DSP加速器、射频发射芯片。在ISM-2.4 GHz波段,射频物理层使用射频直接上变频架构,通过FSK/OOK (on-off-keying)的数据调制方式;重点优化基于PLL的频率综合器(PLL-FS)与可开关的E类功率放大器(PA-E);PLL-FS具有低相位噪声(?119 dBc/Hz@1 MHz)、锁定时间短(28~60 us)、环路特性好的特点;PA优化了输出功率(4~5 dBm)、功率增加效率PAE(25%)、S-参数等。流水EEG-DSP负责整体系统控制、数据缓存、精简无线信道编码以及输出码流调制射频电路。设计利用Cadence Co.的SpecterRF软件、Synopsys Co.的系列数字软件/Caliber软件进行了功能仿真/物理版图验收,设计使用SmicRF180 nm数模混合工艺进行了加工,流片回来的测试结果表明EEG-DSP与射频发射芯片可以满足实际应用。

A NEW QUANTITATIVE DETECTION METHOD OF RECOMBINANT CFP10-ESAT6 AMALGAMATION PROTEINS FROM MYCOBACTERIUM TUBERCULOSIS BASED ON MICRO-MAGNETIC PROBES STRATEGY

A new rapid,specific and sensitive method for assay of recombinant CFP10-ESAT6 amalgamation proteins from Mycobacterium tuberculosis was proposed.The method used streptavidincoated magnetic beads to enrich the specific biotinylated anti-CFP10 antibody,then adopted a sandwich-type enzyme linked immunosorbent assay technology with two kinds of monoclonal antibodies:biotinylated anti-CFP10 antibody and HRP-labeled anti-CFP10 antibody to identify the target CFP10-ESAT6 proteins,and finally detected chemiluminescence intensity by a small home-made optical sensor.It was shown that,the corresponding chemiluminescence intensity had a good logarithmic linear response to the concentration of CFP10-ESAT6 proteins when ranging at 1~1000 ng/mL,and the correlation coefficient is 0.9937.The proposed method could detect the CFP10-ESAT6 proteins with low detection limit(1 ng/mL)and the detection time could be controlled within 45 min.Compared with commonly used detection methods of M.tuberculosis,this method was easy to operate,faster,and of higher sensitivity.The achievement of the quantitative detection of CFP10-ESAT6 proteins has important scientific significance and wide application prospects in tuberculosis control.

Impaired Spatial Firing Representations of Neurons in the Medial Entorhinal Cortex of the Epileptic Rat Using Microelectrode Arrays

Epilepsy severely impairs the cognitive behavior of patients.It remains unclear whether epilepsy-induced cognitive impairment is associated with neuronal activities in the medial entorhinal cortex(MEC),a region known for its involvement in spatial cognition.To explore this neural mechanism,we recorded the spikes and local field potentials from MEC neurons in lithium-pilocarpine-induced epileptic rats using self-designed microelectrode arrays.Through the open field test,we identified spatial cells exhibiting spatially selective firing properties and assessed their spatial representations in relation to the progression of epilepsy.Meanwhile,we analyzed theta oscillations and theta modulation in both excitatory and inhibitory neurons.Furthermore,we used a novel object recognition test to evaluate changes in spatial cognitive ability of epileptic rats.After the epilepsy modeling,the spatial tuning of various types of spatial cells had suffered a rapid and pronounced damage during the latent period(1 to 5 d).Subsequently,the firing characteristics and theta oscillations were impaired.In the chronic period(>10 d),the performance in the novel object experiment deteriorated.In conclusion,our study demonstrates the detrimental effect on spatial representations and electrophysiological properties of MEC neurons in the epileptic latency,suggesting the potential use of these changes as a"functional biomarker"for predicting cognitive impairment caused by epilepsy.

Recent advances and research progress on microsystems and bioeffects of terahertz neuromodulation

Terahertz waves can interact with the nervous system of organisms under certain conditions.Compared to common optical modulation methods,terahertz waves have the advantages of low photon energy and low risk;therefore,the use of terahertz waves to regulate the nervous system is a promising new method of neuromodulation.However,most of the research has focused on the use of terahertz technology for biodetection,while relatively little research has been carried out on the biological effects of terahertz radiation on the nervous system,and there are almost no review papers on this topic.In the present article,we begin by reviewing principles and objects of research regarding the biological effects of terahertz radiation and summarizing the current state of related research from a variety of aspects,including the bioeffects of terahertz radiation on neurons in vivo and in vitro,novel regulation and detection methods with terahertz radiation devices and neural microelectrode arrays,and theoretical simulations of neural information encoding and decoding.In addition,we discuss the main problems and their possible causes and give some recommendations on possible future breakthroughs.This paper will provide insight and assistance to researchers in the fields of neuroscience,terahertz technology and biomedicine.

Real-time simultaneous recording of electrophysiological activities and dopamine overflow in the deep brain nuclei of a non-human primate with Parkinson’s disease using nano-based microelectrode arrays

Parkinson’s disease(PD)is characterized by a progressive degeneration of nigrostriatal dopaminergic neurons.The precise mechanisms are still unknown.Since the neuronal communications are inherently electrical and chemical in nature,dual-mode detection of PD-related neuroelectrical and neurochemical information is essential for PD research.Subthalamic nucleus(STN)highfrequency stimulation(HFS)can improve most symptoms of PD patients and decrease the dosage of antiparkinsonian drugs.The mechanism of STN-HFS for PD still remains elusive.In this study,a silicon-based dual-mode microelectrode array(MEA)probe was designed and fabricated,and systematic dual-mode detection methods were established.The recording sites were modified using Pt nanoparticles and Nafion to improve the signal-to-noise(SNR)ratio.To evaluate its applicability to PD research,in vivo electrophysiological and electrochemical detection was performed in normal and hemiparkinsonian models,respectively.Through comparison of the dual-mode signals,we demonstrated the following in a PD monkey:(1)the maximum dopamine concentration in the striatum decreased by 90%;(2)the spike firing frequency increased significantly,especially in the region of the cortex;(3)the spectrogram analysis showed that much power existed in the 0–10 Hz frequency band;and(4)following repeated subthalamic nucleus high-frequency stimulation trials,the level of DA in the striatum increased by 16.5μM,which led to a better elucidation of the mechanism of HFS.The dual-mode MEA probe was demonstrated to be an effective tool for the study of neurological disorders.

Grid cell remapping under three-dimensional object and social landmarks detected by implantable microelectrode arrays for the medial entorhinal cortex

Grid cells with stable hexagonal firing patterns in the medial entorhinal cortex(MEC)carry the vital function of serving as a metric for the surrounding environment.Whether this mechanism processes only spatial information or involves nonspatial information remains elusive.Here,we fabricated an MEC-shaped microelectrode array(MEA)to detect the variation in neural spikes and local field potentials of the MEC when rats forage in a square enclosure with a planar,three-dimensional object and social landmarks in sequence.The results showed that grid cells exhibited rate remapping under social conditions in which spike firing fields closer to the social landmark had a higher firing rate.Furthermore,global remapping showed that hexagonal firing patterns were rotated and scaled when the planar landmark was replaced with object and social landmarks.In addition,when grid cells were activated,the local field potentials were dominated by the theta band(5–8 Hz),and spike phase locking was observed at troughs of theta oscillations.Our results suggest the pattern separation mechanism of grid cells in which the spatial firing structure and firing rate respond to spatial and social information,respectively,which may provide new insights into how the brain creates a cognitive map.

Wireless closed-loop deep brain stimulation using microelectrode array probes

Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.