This paper introduces in details a kind of silicon-based microelectrode array. MEMS (micro-electromechanical system) technology is used in the fabrication of the microelectrode array, which is designed to perform sign...This paper introduces in details a kind of silicon-based microelectrode array. MEMS (micro-electromechanical system) technology is used in the fabrication of the microelectrode array, which is designed to perform signal recording and electrical stimulation for nerves in neural engineering. A simple fabrication process is developed. An improved model of microelectrodes is brought forward and successfully validated by the excellent match between circuit simulations and electrical measurements, including both magnitude and phase of microelectrode impedance. Compared with the simple one that is usually used, the improved model is believed to be an advance and more accurate. This modeling helps to improve the design of microelectrodes and understand the behavior of interface between electrode and cell. Furthermore, the microelectrode is proved to be a feasible tool for researches in neural engineering by successfully recording neural activities of sciatic nerve of a bullfrog.展开更多
The emerging field of neuroprosthetics is focused on design and implementation of neural prostheses to restore some of the lost neural functions. Remarkable progress has been reported at most bioelectronic levels—par...The emerging field of neuroprosthetics is focused on design and implementation of neural prostheses to restore some of the lost neural functions. Remarkable progress has been reported at most bioelectronic levels—particularly the various brain-machine interfaces (BMIs)—but the electrode-tissue contacts (ETCs) remain one of the major obstacles. The success of these BMIs relies on electrodes which are in contact with the neural tissue. Biological response to chronic implantation of Microelectrode arrays (MEAs) is an essential factor in determining a successful electrode design. By altering the material compositions and geometries of the arrays, fabrication techniques of MEAs insuring these ETCs try to obtain consistent recording signals from small groups of neurons without losing microstimulation capabilities, while maintaining low-impedance pathways for charge injection, high-charge transfer, and high-spatial resolution in recent years. So far, none of these attempts have led to a major breakthrough. Clearly, much work still needs to be done to accept a standard model of MEAs for clinical purposes. In this paper, we review different microfabrication techniques of MEAs with their advantages and drawbacks, and comment on various coating materials to enhance electrode performance. Then, we propose high-density, three-dimensional (3D), silicon-based MEAs using micromachining methods. The geometries that will be used include arrays of penetrating variable-height probes.展开更多
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,...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.展开更多
Recent studies demonstrated that a functional brain network could be regarded as a complex network.With the help of network theory,neuroscientists can identify common organizational principles of the functional brain ...Recent studies demonstrated that a functional brain network could be regarded as a complex network.With the help of network theory,neuroscientists can identify common organizational principles of the functional brain networks.As a consequence,some non-random organizational features,such as"small world"(most of the nodes are not connected directly but can communicate with few intermediate relay steps)and"rich club"(nodes that are rich in connections tend to form strongly interconnected clubs),have been found in functional brain network.Recently,the"small world"organizational feature of neuronal functional networks in vitro was found to be influenced by external applications.However,little is known about the influence of chronic electrical stimulation on functional networks of dissociated cortical cultures during network development.In the present study,cortical cultures were electrically stimulated at a frequency of 0,0.02,and 0.2 Hz,between 7 and 26 days in vitro(DIV).The spontaneous activity of the cortical cultures was recorded using MEAs.Next,a cross-covariance method and graph theory were applied to investigate organizational feature of functional networks.Our results showed that over 3 weeks of stimulation,the network density significantly increased with maturation in the control and 0.02 Hz stimulation groups,but not in 0.2 Hz stimulation groups.Moreover,all the cultures had a small-world topology at 14,18,22,and 26 DIV,free from the effect of chronic electrical stimulation.Besides,we found an asymmetry effect that partial electrical stimulation inhibited the formation of node connections in stimulated areas.This effect was more pronounced at 0.2 Hz than at 0.02 Hz stimulation.Our results suggest that electrical stimulation does not affect the small-world properties of neural cultures.Instead,electrical stimulation modulates connectivity patterns,and neurons within the stimulated area are less connected than neurons outside the stimulated area.展开更多
Brain-machine interface (BMI) has been developed due to its possibility to cure severe body paralysis. This technology has been used to realize the direct control of prosthetic devices,such as robot arms,computer curs...Brain-machine interface (BMI) has been developed due to its possibility to cure severe body paralysis. This technology has been used to realize the direct control of prosthetic devices,such as robot arms,computer cursors,and paralyzed muscles. A variety of neural decoding algorithms have been designed to explore relationships between neural activities and movements of the limbs. In this paper,two novel neural decoding methods based on probabilistic neural network (PNN) in rats were introduced,the PNN decoder and the modified PNN (MPNN) decoder. In the ex-periment,rats were trained to obtain water by pressing a lever over a pressure threshold. Microelectrode array was implanted in the motor cortex to record neural activity,and pressure was recorded by a pressure sensor synchronously. After training,the pressure values were estimated from the neural signals by PNN and MPNN decoders. Their per-formances were evaluated by a correlation coefficient (CC) and a mean square error (MSE). The results show that the MPNN decoder,with a CC of 0.8657 and an MSE of 0.2563,outperformed the traditionally-used Wiener filter (WF) and Kalman filter (KF) decoders. It was also observed that the discretization level did not affect the MPNN performance,indicating that the MPNN decoder can handle different tasks in BMI system,including the detection of movement states and estimation of continuous kinematic parameters.展开更多
The electrical excitability of neural networks is influenced by different environmental factors. Effective and simple methods are required to objectively and quantitatively evaluate the influence of such factors, incl...The electrical excitability of neural networks is influenced by different environmental factors. Effective and simple methods are required to objectively and quantitatively evaluate the influence of such factors, including variations in temperature and pharmaceutical dosage. The aim of this paper was to introduce ‘the voltage threshold measurement method＇, which is a new method using microelectrode arrays that can quantitatively evaluate the influence of different factors on the electrical excitability of neural networks. We sought to verify the feasibility and efficacy of the method by studying the effects of acetylcholine, ethanol, and temperature on hippocampal neuronal networks and hippocampal brain slices. First, we determined the voltage of the stimulation pulse signal that elicited action potentials in the two types of neural networks under normal conditions. Second, we obtained the voltage thresholds for the two types of neural networks under different concentrations of acetylcholine, ethanol, and different temperatures. Finally, we obtained the relationship between voltage threshold and the three influential factors. Our results indicated that the normal voltage thresholds of the hippocampal neuronal network and hippocampal slice preparation were 56 and 31 m V, respectively. The voltage thresholds of the two types of neural networks were inversely proportional to acetylcholine concentration, and had an exponential dependency on ethanol concentration. The curves of the voltage threshold and the temperature of the medium for the two types of neural networks were U-shaped. The hippocampal neuronal network and hippocampal slice preparations lost their excitability when the temperature of the medium decreased below 34 and 33°C or increased above 42 and 43°C, respectively. These results demonstrate that the voltage threshold measurement method is effective and simple for examining the performance/excitability of neuronal networks.展开更多
A prototype of hybrid neural recording interface has been developed for extracellular neural recording. It consists of a silicon-based plane microelectrode array and a CMOS low noise neural amplifier chip. The neural ...A prototype of hybrid neural recording interface has been developed for extracellular neural recording. It consists of a silicon-based plane microelectrode array and a CMOS low noise neural amplifier chip. The neural amplifier chip is designed and implemented in 0.18 μm N-well CMOS 1P6M technology. The area of the neural preamplifier is only 0.042 mm2 with a gain of 48.3 dB. The input equivalent noise is 4.73 btVrms within pass bands of 4 kHz. To avoid cable tethering for high dense mul- tichannel neural recording interface and make it compact, flip-chip bonding is used to integrate the preamplifier chip and the microelectrode together. The hybrid device measures 3 mm×5.5 mm×330μm, which is convenient for implant or in-vivo neu- ral recording. The hybrid device was testified in in-vivo experiment. Neural signals were recorded from hippocampus region of anesthetized Sprague Dawley rats successfully.展开更多
Recording neural signals from delicate autonomic nerves is a challenging task that requires the development of a lowinvasive neural interface with highly selective,micrometer-sized electrodes.This paper reports on the...Recording neural signals from delicate autonomic nerves is a challenging task that requires the development of a lowinvasive neural interface with highly selective,micrometer-sized electrodes.This paper reports on the development of a three-dimensional(3D)protruding thin-film microelectrode array(MEA),which is intended to be used for recording low-amplitude neural signals from pelvic nervous structures by penetrating the nerves transversely to reduce the distance to the axons.Cylindrical gold pillars(O 20 or 50μm,~60μm height)were fabricated on a micromachined polyimide substrate in an electroplating process.Their sidewalls were insulated with parylene C,and their tips were optionally modified by wet etching and/or the application of a titanium nitride(TiN)coating.The microelectrodes modified by these combined techniques exhibited low impedances(~7 kΩ at 1 kHz for ∅ 50μm microelectrode with the exposed surface area of~5000μm^(2))and low intrinsic noise levels.Their functionalities were evaluated in an ex vivo pilot study with mouse retinae,in which spontaneous neuronal spikes were recorded with amplitudes of up to 66μV.This novel process strategy for fabricating flexible,3D neural interfaces with low-impedance microelectrodes has the potential to selectively record neural signals from not only delicate structures such as retinal cells but also autonomic nerves with improved signal quality to study neural circuits and develop stimulation strategies in bioelectronic medicine,e.g.,for the control of vital digestive functions.展开更多
The paper is aimed to investigate the adhesion and growth of neural cells on different microelectrode surfaces and their possible mechanism, thereby an optimum interfacial material or substrate for neural microelectro...The paper is aimed to investigate the adhesion and growth of neural cells on different microelectrode surfaces and their possible mechanism, thereby an optimum interfacial material or substrate for neural microelectrode can be chosen. Three different materials including platinum, gold, and pyrolyzed photoresist derived carbon material, in the forms of plasma-treated and non-treated ones, were tested. Surface properties of the microelectrodes in terms of surface morphology and wettability were examined; then their biocompatibility was tested by co-culturing with SK-N-SH neuroblastoma cells. Results of experiments demonstrated that, compared with platinum and gold, carbon could be a better substrate for cell adhesion and growth,especially for the plasma-treated carbon surface. The high wetting property of plasma-treated carbon accounted for the preferable adhesion of cell on its surface. Therefore, plasma-treated carbon can potentially be employed for fabrication of biocompatible and stable neural electrodes, which is beneficial for neural engineering research, such as regeneration from injury or disease therapy of neural system.展开更多
Rhesus monkey models of Parkinson＇s disease were induced by injection of N-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine. Neural firings were recorded using microelectrodes placed in the interna segment of the globus p...Rhesus monkey models of Parkinson＇s disease were induced by injection of N-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine. Neural firings were recorded using microelectrodes placed in the interna segment of the globus pallidus. The wavelets and power spectra show gradual power reduction during the disease process along with increased firing rates in the Parkinson＇s disease state. Singular values of coefficients decreased considerably during tremor-related activity as well as in the Parkinson＇s disease state compared with normal signals, revealing that higher-frequency components weaken when Parkinson＇s disease occurs. We speculate that the death of neurons could be reflected by irregular frequency spike trains, and that wavelet packet decomposition can effectively detect the degradation of neurons and the loss of information transmission in the neural circuitry.展开更多
基金Supported by the Natural Science Foundation of Zhejiang Province of China (Grant No. Y106448)State Key Laboratories of Transducer Technology (Grant No. SKT0506)
文摘This paper introduces in details a kind of silicon-based microelectrode array. MEMS (micro-electromechanical system) technology is used in the fabrication of the microelectrode array, which is designed to perform signal recording and electrical stimulation for nerves in neural engineering. A simple fabrication process is developed. An improved model of microelectrodes is brought forward and successfully validated by the excellent match between circuit simulations and electrical measurements, including both magnitude and phase of microelectrode impedance. Compared with the simple one that is usually used, the improved model is believed to be an advance and more accurate. This modeling helps to improve the design of microelectrodes and understand the behavior of interface between electrode and cell. Furthermore, the microelectrode is proved to be a feasible tool for researches in neural engineering by successfully recording neural activities of sciatic nerve of a bullfrog.
文摘The emerging field of neuroprosthetics is focused on design and implementation of neural prostheses to restore some of the lost neural functions. Remarkable progress has been reported at most bioelectronic levels—particularly the various brain-machine interfaces (BMIs)—but the electrode-tissue contacts (ETCs) remain one of the major obstacles. The success of these BMIs relies on electrodes which are in contact with the neural tissue. Biological response to chronic implantation of Microelectrode arrays (MEAs) is an essential factor in determining a successful electrode design. By altering the material compositions and geometries of the arrays, fabrication techniques of MEAs insuring these ETCs try to obtain consistent recording signals from small groups of neurons without losing microstimulation capabilities, while maintaining low-impedance pathways for charge injection, high-charge transfer, and high-spatial resolution in recent years. So far, none of these attempts have led to a major breakthrough. Clearly, much work still needs to be done to accept a standard model of MEAs for clinical purposes. In this paper, we review different microfabrication techniques of MEAs with their advantages and drawbacks, and comment on various coating materials to enhance electrode performance. Then, we propose high-density, three-dimensional (3D), silicon-based MEAs using micromachining methods. The geometries that will be used include arrays of penetrating variable-height probes.
基金sponsored by the National Natural Science Foundation of China(L2224042,61988102,T2293731,62121003,61960206012,62171434,61975206 and 61973292)the Frontier Interdisciplinary Project of the Chinese Academy of Sciences(XK2022XXC003)+1 种基金STI 2030-Major Projects 2021ZD0201600,the National Key R&D Program of China(2022YFC2402501)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(GJJSTD20210004).
文摘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.
基金supported by the National Natural Science Fund for Outstanding Young Scholar(Grant No.81622027)the Key Program of the National Key Research and Development Program of China(Grant No.2017YFA0106100)the research fund of PLA of China(Grant Nos.AWS17J011,BWS17J024)。
文摘Recent studies demonstrated that a functional brain network could be regarded as a complex network.With the help of network theory,neuroscientists can identify common organizational principles of the functional brain networks.As a consequence,some non-random organizational features,such as"small world"(most of the nodes are not connected directly but can communicate with few intermediate relay steps)and"rich club"(nodes that are rich in connections tend to form strongly interconnected clubs),have been found in functional brain network.Recently,the"small world"organizational feature of neuronal functional networks in vitro was found to be influenced by external applications.However,little is known about the influence of chronic electrical stimulation on functional networks of dissociated cortical cultures during network development.In the present study,cortical cultures were electrically stimulated at a frequency of 0,0.02,and 0.2 Hz,between 7 and 26 days in vitro(DIV).The spontaneous activity of the cortical cultures was recorded using MEAs.Next,a cross-covariance method and graph theory were applied to investigate organizational feature of functional networks.Our results showed that over 3 weeks of stimulation,the network density significantly increased with maturation in the control and 0.02 Hz stimulation groups,but not in 0.2 Hz stimulation groups.Moreover,all the cultures had a small-world topology at 14,18,22,and 26 DIV,free from the effect of chronic electrical stimulation.Besides,we found an asymmetry effect that partial electrical stimulation inhibited the formation of node connections in stimulated areas.This effect was more pronounced at 0.2 Hz than at 0.02 Hz stimulation.Our results suggest that electrical stimulation does not affect the small-world properties of neural cultures.Instead,electrical stimulation modulates connectivity patterns,and neurons within the stimulated area are less connected than neurons outside the stimulated area.
基金Project supported by the National Natural Science Foundation of China (Nos. 30800287 and 60703038)the Natural Science Foundation of Zhejiang Province, China (No. Y2090707)
文摘Brain-machine interface (BMI) has been developed due to its possibility to cure severe body paralysis. This technology has been used to realize the direct control of prosthetic devices,such as robot arms,computer cursors,and paralyzed muscles. A variety of neural decoding algorithms have been designed to explore relationships between neural activities and movements of the limbs. In this paper,two novel neural decoding methods based on probabilistic neural network (PNN) in rats were introduced,the PNN decoder and the modified PNN (MPNN) decoder. In the ex-periment,rats were trained to obtain water by pressing a lever over a pressure threshold. Microelectrode array was implanted in the motor cortex to record neural activity,and pressure was recorded by a pressure sensor synchronously. After training,the pressure values were estimated from the neural signals by PNN and MPNN decoders. Their per-formances were evaluated by a correlation coefficient (CC) and a mean square error (MSE). The results show that the MPNN decoder,with a CC of 0.8657 and an MSE of 0.2563,outperformed the traditionally-used Wiener filter (WF) and Kalman filter (KF) decoders. It was also observed that the discretization level did not affect the MPNN performance,indicating that the MPNN decoder can handle different tasks in BMI system,including the detection of movement states and estimation of continuous kinematic parameters.
基金supported by the National Natural Sciences Foundation of China,No.61534003,61076118the Innovation Foundation for State Key Laboratory of the Ministry of Science and Technology,China,No.2016-2018a grant from the Open Projects of Key Laboratory of Child Development and Learning of the Ministry of Education of China,No.CDLS201205
文摘The electrical excitability of neural networks is influenced by different environmental factors. Effective and simple methods are required to objectively and quantitatively evaluate the influence of such factors, including variations in temperature and pharmaceutical dosage. The aim of this paper was to introduce ‘the voltage threshold measurement method＇, which is a new method using microelectrode arrays that can quantitatively evaluate the influence of different factors on the electrical excitability of neural networks. We sought to verify the feasibility and efficacy of the method by studying the effects of acetylcholine, ethanol, and temperature on hippocampal neuronal networks and hippocampal brain slices. First, we determined the voltage of the stimulation pulse signal that elicited action potentials in the two types of neural networks under normal conditions. Second, we obtained the voltage thresholds for the two types of neural networks under different concentrations of acetylcholine, ethanol, and different temperatures. Finally, we obtained the relationship between voltage threshold and the three influential factors. Our results indicated that the normal voltage thresholds of the hippocampal neuronal network and hippocampal slice preparation were 56 and 31 m V, respectively. The voltage thresholds of the two types of neural networks were inversely proportional to acetylcholine concentration, and had an exponential dependency on ethanol concentration. The curves of the voltage threshold and the temperature of the medium for the two types of neural networks were U-shaped. The hippocampal neuronal network and hippocampal slice preparations lost their excitability when the temperature of the medium decreased below 34 and 33°C or increased above 42 and 43°C, respectively. These results demonstrate that the voltage threshold measurement method is effective and simple for examining the performance/excitability of neuronal networks.
基金supported in part by the National Natural Science Foundation of China(Grant Nos.61076023,61275200,31070965)the National Basic Research Program of China("973" project)(Grant No.2011CB933203)the National High-Tech Research and Development Program of China("863" Project)(Grant No.2012AA030308)
文摘A prototype of hybrid neural recording interface has been developed for extracellular neural recording. It consists of a silicon-based plane microelectrode array and a CMOS low noise neural amplifier chip. The neural amplifier chip is designed and implemented in 0.18 μm N-well CMOS 1P6M technology. The area of the neural preamplifier is only 0.042 mm2 with a gain of 48.3 dB. The input equivalent noise is 4.73 btVrms within pass bands of 4 kHz. To avoid cable tethering for high dense mul- tichannel neural recording interface and make it compact, flip-chip bonding is used to integrate the preamplifier chip and the microelectrode together. The hybrid device measures 3 mm×5.5 mm×330μm, which is convenient for implant or in-vivo neu- ral recording. The hybrid device was testified in in-vivo experiment. Neural signals were recorded from hippocampus region of anesthetized Sprague Dawley rats successfully.
基金financed by the German Federal Ministry of Education and Research(BMBF)within the funding program"Individualisierte Medizintechnik"under grant 13GW0271C(NEPTUN)received financial support from the State Ministry of Baden-Wuerttemberg for Economic Affairs,Labor and Tourism+1 种基金Thomas Stieglitz was partly supported by the BrainLinks-BrainTools Cluster of Excellence funded by the German Research Foundation-DFG(EXC 1086)funded by the Federal Ministry of Economics,Science and Arts of Baden-Württemberg within the sustainability program for projects of excellence initiative II.
文摘Recording neural signals from delicate autonomic nerves is a challenging task that requires the development of a lowinvasive neural interface with highly selective,micrometer-sized electrodes.This paper reports on the development of a three-dimensional(3D)protruding thin-film microelectrode array(MEA),which is intended to be used for recording low-amplitude neural signals from pelvic nervous structures by penetrating the nerves transversely to reduce the distance to the axons.Cylindrical gold pillars(O 20 or 50μm,~60μm height)were fabricated on a micromachined polyimide substrate in an electroplating process.Their sidewalls were insulated with parylene C,and their tips were optionally modified by wet etching and/or the application of a titanium nitride(TiN)coating.The microelectrodes modified by these combined techniques exhibited low impedances(~7 kΩ at 1 kHz for ∅ 50μm microelectrode with the exposed surface area of~5000μm^(2))and low intrinsic noise levels.Their functionalities were evaluated in an ex vivo pilot study with mouse retinae,in which spontaneous neuronal spikes were recorded with amplitudes of up to 66μV.This novel process strategy for fabricating flexible,3D neural interfaces with low-impedance microelectrodes has the potential to selectively record neural signals from not only delicate structures such as retinal cells but also autonomic nerves with improved signal quality to study neural circuits and develop stimulation strategies in bioelectronic medicine,e.g.,for the control of vital digestive functions.
基金National Basic Research Program of China (973 Program) (No.2011CB707505)National Natural Science Foundations of China(No.30872629,30900315,60906055)National High-Tech R & D Program of China (863 Program) (No.2009AA04Z326)
文摘The paper is aimed to investigate the adhesion and growth of neural cells on different microelectrode surfaces and their possible mechanism, thereby an optimum interfacial material or substrate for neural microelectrode can be chosen. Three different materials including platinum, gold, and pyrolyzed photoresist derived carbon material, in the forms of plasma-treated and non-treated ones, were tested. Surface properties of the microelectrodes in terms of surface morphology and wettability were examined; then their biocompatibility was tested by co-culturing with SK-N-SH neuroblastoma cells. Results of experiments demonstrated that, compared with platinum and gold, carbon could be a better substrate for cell adhesion and growth,especially for the plasma-treated carbon surface. The high wetting property of plasma-treated carbon accounted for the preferable adhesion of cell on its surface. Therefore, plasma-treated carbon can potentially be employed for fabrication of biocompatible and stable neural electrodes, which is beneficial for neural engineering research, such as regeneration from injury or disease therapy of neural system.
基金supported in part by a grant from the National Natural Science Foundation of China,No. 81071150,10872156the National High Technology Research and Development Program of China (863 Program),No.2006AA04Z370
文摘Rhesus monkey models of Parkinson＇s disease were induced by injection of N-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine. Neural firings were recorded using microelectrodes placed in the interna segment of the globus pallidus. The wavelets and power spectra show gradual power reduction during the disease process along with increased firing rates in the Parkinson＇s disease state. Singular values of coefficients decreased considerably during tremor-related activity as well as in the Parkinson＇s disease state compared with normal signals, revealing that higher-frequency components weaken when Parkinson＇s disease occurs. We speculate that the death of neurons could be reflected by irregular frequency spike trains, and that wavelet packet decomposition can effectively detect the degradation of neurons and the loss of information transmission in the neural circuitry.
