159 results on '"Daryl R Kipke"'
Search Results
52. Sensitivity of the cochlear nucleus octopus cell to synaptic and membrane properties: A modeling study
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Kenneth L. Levy and Daryl R. Kipke
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Acoustics and Ultrasonics ,Chemistry ,Conductance ,Depolarization ,Neurophysiology ,Cell morphology ,Cochlear nucleus ,medicine.anatomical_structure ,Arts and Humanities (miscellaneous) ,octopus (software) ,medicine ,Excitatory postsynaptic potential ,Biophysics ,Soma - Abstract
Octopus cells of the posteroventral cochlear nucleus precisely fire at the onset of short-duration tone bursts, followed by little sustained activity. While this characteristic onset response has been described in experimental studies, its underlying mechanisms are not completely known. The objective of this study was to investigate these mechanisms through a sensitivity analysis of selected parameters of a compartmental model of the octopus cell. The parameters relate to cell morphology, passive electrical properties, synaptic inputs, and active channels. The modeled responses were used to evaluate the effects of four postulated mechanisms on the onset response: the cell’s small membrane time constant, the cell’s numerous weakly effective excitatory inputs, increases in spike threshold caused by sustained depolarization, and electrical loading of the soma by the dendrites. Simulations indicate that the model’s onset response to tone bursts is an emergent property of multiple cell parameters that is best predicted by the ratio of synaptic conductance density to membrane leakage conductance density and by the level of sustained depolarization during the tone burst.
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- 1997
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53. A computational model of the cochlear nucleus octopus cell
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Kenneth L. Levy and Daryl R. Kipke
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Acoustics and Ultrasonics ,biology ,Chemistry ,Cell ,Dendrite ,Neurophysiology ,Cochlear nucleus ,Octopus ,medicine.anatomical_structure ,Arts and Humanities (miscellaneous) ,biology.animal ,medicine ,Excitatory postsynaptic potential ,Soma ,Neuroscience ,Cell based - Abstract
Cochlear nucleus octopus cells are characterized by a temporally precise response at the onset of tone bursts and other phasic stimuli. The objectives of this study were to develop a biologically plausible model of an octopus cell based on typical morphological and physiological properties, and to describe the model’s ability to simulate responses of octopus cells and onset units. The compartmental model represents the basic morphology of octopus cells with a single passive, equivalent dendrite and a lumped, active soma. Independent, excitatory synaptic inputs are distributed on the dendrite and soma to represent inputs from 60 or 120 auditory-nerve fibers. The computed model responses were evaluated using simulated current injections, short-duration tone bursts, and several other types of stimuli. With biologically plausible values for the model parameters, the representation of 60 auditory-nerve inputs yields responses consistent with an OL unit while the representation of 120 inputs yields responses co...
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- 1997
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54. Effects of electrical stimulation of cutaneous afferents on corticospinal transmission of tremor signals in patients with Parkinson's disease
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Ning Lan, Daryl R. Kipke, Manzhao Hao, and Xin He
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Flexor Carpi Ulnaris ,Parkinson's disease ,medicine.diagnostic_test ,business.industry ,Stimulation ,Electromyography ,musculoskeletal system ,medicine.disease ,Inhibitory postsynaptic potential ,Spinal cord ,Biceps ,nervous system diseases ,body regions ,medicine.anatomical_structure ,Medicine ,Resting tremor ,business ,Neuroscience - Abstract
It has been hypothesized that propriospinal neurons (PNs) in the C3-C4 spinal cord mediates cortical motor commands to the peripheral muscles during tremor in patients with Parkinson's disease (PD). However, there has been no direct evidence so far to support the role of PN in transmitting tremor commands. In this paper, we report the positive correlation of cutaneous afferents with reduction in tremor amplitude and frequency in PD patients. Resting tremor and EMGs of biceps, triceps, flexor digitorum superficialis (FDS), extensor digitorum (ED), flexor carpi ulnaris (FCU) and extensor carpi radialis (ECR) muscles were recorded while transcutaneous electrical stimulation (TES) was applied to the dorsal hand skin of PD subjects. We observed instant suppression of tremor amplitude and EMGs occurring immediately at the start of electrical stimulation. However at the end of stimulation, the tremor amplitude and EMGs showed a quick recovery to the level prior to stimulation. Spectral analysis indicated that cutaneous afferents also have a long-lasting memory effect on the tremor frequency, i.e. the tremor frequency post stimulation did not recover to the value prior to stimulation. Preliminary results implied that the reduction in tremor amplitude and EMGs could be due to the inhibitory effects of cutaneous afferents to PNs, supporting the hypothesis that the PN network is involved in transmission of cortical tremor commands to peripheral muscles.
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- 2013
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55. Bi-directional Optrode for quantitative prediction of neural interface failure
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Parshant Kumar, John LeBlanc, G. Cook, V. Mittal, G. E. Perlin, Daryl R. Kipke, Bryan McLaughlin, Komal Kampasi, Carlos A. Segura, and Anil Kumar H. Achyuta
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Brain implant ,Cortical tissue ,Materials science ,medicine.anatomical_structure ,Cerebral cortex ,Rat model ,medicine ,Tissue density ,Neurophysiology ,Optode ,Brain–computer interface ,Biomedical engineering - Abstract
An optical-electrical neural `Optrode' is developed for quantitative optical spectroscopic assessment of cortical tissue damage around a neural implant. In contrast to other Optrodes which illuminate tissue for neural activation, this work uses bi-directional waveguides to obtain spectroscopic information from the tissue. An optical assessment has the potential for providing a real-time histological assessment, by quantifying changes in absorption and scattering properties associated with oxygenation and tissue density around the neural probe, in contrast to impedance spectroscopy which provides limited insight. Optrode performance is characterized in optical tissue phantoms and a proof-of-concept chronic rat model is developed. Optrodes were chronically implanted in rat cerebral cortex. The pilot study demonstrates feasibility for chronic optical assessment. Future Optrodes may lead to high throughput and real-time assessments for studying the dynamic nature of the foreign body response in neural tissue.
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- 2013
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56. High gamma power in ECoG reflects cortical electrical stimulation effects on unit activity in layers V/VI
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Mark J. Lehmkuhle, Daryl R. Kipke, and Azadeh Yazdan-Shahmorad
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Male ,medicine.diagnostic_test ,Gamma power ,Chemistry ,Bone Screws ,Biomedical Engineering ,Motor Cortex ,Stimulation ,Electroencephalography ,Local field potential ,Brain Waves ,Article ,Electric Stimulation ,Electrodes, Implanted ,Rats ,Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,Cortex (anatomy) ,medicine ,Electrode array ,Animals ,Primary motor cortex ,Neuroscience ,Motor cortex - Abstract
Objective. Cortical electrical stimulation (CES) has been used extensively in experimental neuroscience to modulate neuronal or behavioral activity, which has led this technique to be considered in neurorehabilitation. Because the cortex and the surrounding anatomy have irregular geometries as well as inhomogeneous and anisotropic electrical properties, the mechanism by which CES has therapeutic effects is poorly understood. Therapeutic effects of CES can be improved by optimizing the stimulation parameters based on the effects of various stimulation parameters on target brain regions. Approach. In this study we have compared the effects of CES pulse polarity, frequency, and amplitude on unit activity recorded from rat primary motor cortex with the effects on the corresponding local field potentials (LFP), and electrocorticograms (ECoG). CES was applied at the surface of the cortex and the unit activity and LFPs were recorded using a penetrating electrode array, which was implanted below the stimulation site. ECoGs were recorded from the vicinity of the stimulation site. Main results. Time–frequency analysis of LFPs following CES showed correlation of gamma frequencies with unit activity response in all layers. More importantly, high gamma power of ECoG signals only correlated with the unit activity in lower layers (V–VI) following CES. Time–frequency correlations, which were found between LFPs, ECoGs and unit activity, were frequency- and amplitude-dependent. Significance. The signature of the neural activity observed in LFP and ECoG signals provides a better understanding of the effects of stimulation on network activity, representative of large numbers of neurons responding to stimulation. These results demonstrate that the neurorehabilitation and neuroprosthetic applications of CES targeting layered cortex can be further improved by using field potential recordings as surrogates to unit activity aimed at optimizing stimulation efficacy. Likewise, the signatures of unit activity observed as changes in high gamma power in ECoGs suggest that future cortical stimulation studies could rely on less invasive feedback schemes that incorporate surface stimulation with ECoG reporting of stimulation efficacy.
- Published
- 2013
57. Whole Animal Perfusion Fixation for Rodents
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Gregory J. Gage, William Shain, and Daryl R. Kipke
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Tissue Fixation ,Polymers ,Physiology ,brain ,preservation ,General Chemical Engineering ,Biomedical Engineering ,vascular system ,Intact brain ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,chemistry.chemical_compound ,Fixatives ,0302 clinical medicine ,Paraformaldehyde ,Formaldehyde ,Animals ,Fixative ,030304 developmental biology ,Fixation (histology) ,0303 health sciences ,fixation ,General Immunology and Microbiology ,General Neuroscience ,physiological pressures ,Anatomy ,Rats ,Perfusion ,Vascular network ,chemistry ,Circulatory system ,WHOLE ANIMAL ,030217 neurology & neurosurgery ,Neuroscience ,Issue 65 - Abstract
The goal of fixation is to rapidly and uniformly preserve tissue in a life-like state. While placing tissue directly in fixative works well for small pieces of tissue, larger specimens like the intact brain pose a problem for immersion fixation because the fixative does not reach all regions of the tissue at the same rate (5,7). Often, changes in response to hypoxia begin before the tissue can be preserved (12). The advantage of directly perfusing fixative through the circulatory system is that the chemical can quickly reach every corner of the organism using the natural vascular network. In order to utilize the circulatory system most effectively, care must be taken to match physiological pressures (3). It is important to note that physiological pressures are dependent on the species used. Techniques for perfusion fixation vary depending on the tissue to be fixed and how the tissue will be processed following fixation. In this video, we describe a low-cost, rapid, controlled and uniform fixation procedure using 4% paraformaldehyde perfused via the vascular system: through the heart of the rat to obtain the best possible preservation of the brain for immunohistochemistry. The main advantage of this technique (vs. gravity-fed systems) is that the circulatory system is utilized most effectively.
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- 2012
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58. Navigating conjugated polymer actuated neural probes in a brain phantom
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Elisabeth Smela, Daryl R. Kipke, and Eugene D. Daneshvar
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chemistry.chemical_classification ,Materials science ,Bilayer ,Nanotechnology ,Polymer ,Conjugated system ,Imaging phantom ,chemistry.chemical_compound ,chemistry ,Parylene ,Electrode ,Electroactive polymers ,Actuator ,Biomedical engineering - Abstract
Neural probe insertion methods have a direct impact on the longevity of the device in the brain. Initial tissue and vascular damage caused by the probe entering the brain triggers a chronic tissue response that is known to attenuate neural recordings and ultimately encapsulate the probes. Smaller devices have been found to evoke reduced inflammatory response. One way to record from undamaged neural networks may be to position the electrode sites away from the probe. To investigate this approach, we are developing probes with controllably movable electrode projections, which would move outside of the zone that is damaged by the insertion of the larger probe. The objective of this study was to test the capability of conjugated polymer bilayer actuators to actuate neural electrode projections from a probe shank into a transparent brain phantom. Parylene neural probe devices, having five electrode projections with actuating segments and with varying widths (50 - 250 μm) and lengths (200 - 1000 μm) were fabricated. The electroactive polymer polypyrrole (PPy) was used to bend or flatten the projections. The devices were inserted into the brain phantom using an electronic microdrive while simultaneously activating the actuators. Deflections were quantified based on video images. The electrode projections were successfully controlled to either remain flat or to actuate out-of-plane and into the brain phantom during insertion. The projection width had a significant effect on their ability to deflect within the phantom, with thinner probes deflecting but not the wider ones. Thus, small integrated conjugated polymer actuators may enable multiple neuro-experiments and applications not possible before.
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- 2012
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59. Voltage Biasing, Cyclic Voltammetry, & Electrical Impedance Spectroscopy for Neural Interfaces
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Thomas J. Richner, Daryl R. Kipke, Seth J. Wilks, Justin C. Williams, Sarah K. Brodnick, and Kevin J. Otto
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neuroprosthesis ,Materials science ,General Chemical Engineering ,0206 medical engineering ,rejuvenation ,02 engineering and technology ,Electrochemistry ,General Biochemistry, Genetics and Molecular Biology ,User-Computer Interface ,03 medical and health sciences ,0302 clinical medicine ,neural implant ,Animals ,Electrical impedance ,Neurons ,General Immunology and Microbiology ,General Neuroscience ,brain-computer interface ,Biasing ,Electrochemical Techniques ,electrode ,electrode-tissue interface ,020601 biomedical engineering ,Electrodes, Implanted ,Rats ,Dielectric spectroscopy ,neural engineering ,Brain implant ,electrochemistry ,Dielectric Spectroscopy ,Electrode ,Issue 60 ,Cyclic voltammetry ,030217 neurology & neurosurgery ,Neuroscience ,Voltage ,Biomedical engineering - Abstract
Electrical impedance spectroscopy (EIS) and cyclic voltammetry (CV) measure properties of the electrode-tissue interface without additional invasive procedures, and can be used to monitor electrode performance over the long term. EIS measures electrical impedance at multiple frequencies, and increases in impedance indicate increased glial scar formation around the device, while cyclic voltammetry measures the charge carrying capacity of the electrode, and indicates how charge is transferred at different voltage levels. As implanted electrodes age, EIS and CV data change, and electrode sites that previously recorded spiking neurons often exhibit significantly lower efficacy for neural recording. The application of a brief voltage pulse to implanted electrode arrays, known as rejuvenation, can bring back spiking activity on otherwise silent electrode sites for a period of time. Rejuvenation alters EIS and CV, and can be monitored by these complementary methods. Typically, EIS is measured daily as an indication of the tissue response at the electrode site. If spikes are absent in a channel that previously had spikes, then CV is used to determine the charge carrying capacity of the electrode site, and rejuvenation can be applied to improve the interface efficacy. CV and EIS are then repeated to check the changes at the electrode-tissue interface, and neural recordings are collected. The overall goal of rejuvenation is to extend the functional lifetime of implanted arrays.
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- 2012
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60. Acquiring Brain Signals from within the Brain
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Daryl R. Kipke, Kevin J. Otto, and Kip A. Ludwig
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Computer science - Published
- 2012
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61. Theoretical analysis of intracortical microelectrode recordings
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Michael A. Moffitt, Scott F. Lempka, Matthew D. Johnson, Daryl R. Kipke, Cameron C. McIntyre, and Kevin J. Otto
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Cerebral Cortex ,Quality Control ,Pyramidal Neuron ,Computer science ,Acoustics ,Pyramidal Cells ,Bandwidth (signal processing) ,Models, Neurological ,Biomedical Engineering ,Intact brain ,Equipment Design ,Article ,Electrodes, Implanted ,Cellular and Molecular Neuroscience ,Microelectrode ,Head model ,Recording electrode ,Electric Impedance ,Thermodynamics ,Computer Simulation ,Extracellular Space ,Electrical impedance ,Device failure ,Microelectrodes ,Algorithms - Abstract
Advanced fabrication techniques have now made it possible to produce microelectrode arrays for recording the electrical activity of a large number of neurons in the intact brain for both clinical and basic science applications. However, the long-term recording performance desired for these applications is hindered by a number of factors that lead to device failure or a poor signal-to-noise ratio (SNR). The goal of this study was to identify factors that can affect recording quality using theoretical analysis of intracortical microelectrode recordings of single-unit activity. Extracellular microelectrode recordings were simulated with a detailed multi-compartment cable model of a pyramidal neuron coupled to a finite element volume conductor head model containing an implanted recording microelectrode. Recording noise sources were also incorporated into the overall modeling infrastructure. The analyses of this study would be very difficult to perform experimentally; however, our model-based approach enabled a systematic investigation of the effects of a large number of variables on recording quality. Our results demonstrate that recording amplitude and noise are relatively independent of microelectrode size, but instead are primarily affected by the selected recording bandwidth, impedance of the electrode-tissue interface, and the density and firing rates of neurons surrounding the recording electrode. This study provides the theoretical groundwork that allows for the design of the microelectrode and recording electronics such that the SNR is maximized. Such advances could help enable the long-term functionality required for chronic neural recording applications.
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- 2011
62. Estimation of electrode location in a rat motor cortex by laminar analysis of electrophysiology and intracortical electrical stimulation
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Daryl R. Kipke, Azadeh Yazdan-Shahmorad, Timothy C. Marzullo, Mark J. Lehmkuhle, Gregory J. Gage, H. Parikh, and Rachel M. Miriani
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Male ,Xylazine ,Materials science ,Biomedical Engineering ,Cellular and Molecular Neuroscience ,Cortex (anatomy) ,medicine ,Animals ,Evoked Potentials ,Polarity reversal ,Neurons ,Anesthetics, Dissociative ,Motor Cortex ,Laminar flow ,Electric Stimulation ,Electrodes, Implanted ,Electrophysiological Phenomena ,Rats ,Electrophysiology ,Microelectrode ,medicine.anatomical_structure ,Electrode ,Linear Models ,Ketamine ,Extracellular Space ,Cortical column ,Neuroscience ,Adrenergic alpha-Agonists ,Microelectrodes ,Algorithms ,Biomedical engineering ,Motor cortex - Abstract
While the development of microelectrode arrays has enabled access to disparate regions of a cortex for neurorehabilitation, neuroprosthetic and basic neuroscience research, accurate interpretation of the signals and manipulation of the cortical neurons depend upon the anatomical placement of the electrode arrays in a layered cortex. Toward this end, this report compares two in vivo methods for identifying the placement of electrodes in a linear array spaced 100 µm apart based on in situ laminar analysis of (1) ketamine-xylazine-induced field potential oscillations in a rat motor cortex and (2) an intracortical electrical stimulation-induced movement threshold. The first method is based on finding the polarity reversal in laminar oscillations which is reported to appear at the transition between layers IV and V in laminar 'high voltage spindles' of the rat cortical column. Analysis of histological images in our dataset indicates that polarity reversal is detected 150.1 ± 104.2 µm below the start of layer V. The second method compares the intracortical microstimulation currents that elicit a physical movement for anodic versus cathodic stimulation. It is based on the hypothesis that neural elements perpendicular to the electrode surface are preferentially excited by anodic stimulation while cathodic stimulation excites those with a direction component parallel to its surface. With this method, we expect to see a change in the stimulation currents that elicits a movement at the beginning of layer V when comparing anodic versus cathodic stimulation as the upper cortical layers contain neuronal structures that are primarily parallel to the cortical surface and lower layers contain structures that are primarily perpendicular. Using this method, there was a 78.7 ± 68 µm offset in the estimate of the depth of the start of layer V. The polarity reversal method estimates the beginning of layer V within ±90 µm with 95% confidence and the intracortical stimulation method estimates it within ±69.3 µm. We propose that these methods can be used to estimate the in situ location of laminar electrodes implanted in the rat motor cortex.
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- 2011
63. Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces
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Daryl R. Kipke, Xiaopei Deng, Karen L. Smith, Paras R. Patel, Joerg Lahann, Nicholas B. Langhals, Nicholas A. Kotov, Huanan Zhang, and Takashi D. Y. Kozai
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Materials science ,Mechanical Engineering ,Composite number ,Nanotechnology ,General Chemistry ,Brain tissue ,engineering.material ,Synaptic Potentials ,Condensed Matter Physics ,Carbon ,Article ,Electrodes, Implanted ,Rats ,Microelectrode ,Neural activity ,Coating ,Mechanics of Materials ,Composite electrode ,Carbon Fiber ,Electrode ,engineering ,Animals ,General Materials Science ,Microelectrodes ,Brain–computer interface - Abstract
Implantable neural microelectrodes that can record extracellular biopotentials from small, targeted groups of neurons are critical for neuroscience research and emerging clinical applications including brain-controlled prosthetic devices. The crucial material-dependent problem is developing microelectrodes that record neural activity from the same neurons for years with high fidelity and reliability. Here, we report the development of an integrated composite electrode consisting of a carbon-fibre core, a poly(p-xylylene)-based thin-film coating that acts as a dielectric barrier and that is functionalized to control intrinsic biological processes, and a poly(thiophene)-based recording pad. The resulting implants are an order of magnitude smaller than traditional recording electrodes, and more mechanically compliant with brain tissue. They were found to elicit much reduced chronic reactive tissue responses and enabled single-neuron recording in acute and early chronic experiments in rats. This technology, taking advantage of new composites, makes possible highly selective and stealthy neural interface devices towards realizing long-lasting implants.
- Published
- 2011
64. Novel multi-sided, microelectrode arrays for implantable neural applications
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Nicholas B. Langhals, David J. Anderson, Daryl R. Kipke, and John P. Seymour
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Male ,Materials science ,Polymers ,Finite Element Analysis ,Biomedical Engineering ,Edge (geometry) ,Xylenes ,Article ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Parylene ,Chemical-mechanical planarization ,Electric Impedance ,Animals ,Electroplating ,Molecular Biology ,Brain ,Multielectrode array ,Prostheses and Implants ,Silicon Dioxide ,Electrophysiological Phenomena ,Rats ,Microelectrode ,chemistry ,Electrode ,Microtechnology ,Microelectrodes ,Microfabrication ,Biomedical engineering - Abstract
A new parylene-based microfabrication process is presented for neural recording and drug delivery applications. We introduce a large design space for electrode placement and structural flexibility with a six mask process. By using chemical mechanical polishing, electrode sites may be created top-side, back-side, or on the edge of the device having three exposed sides. Added surface area was achieved on the exposed edge through electroplating. Poly(3,4-ethylenedioxythiophene) (PEDOT) modified edge electrodes having an 85-μm(2) footprint resulted in an impedance of 200 kΩ at 1 kHz. Edge electrodes were able to successfully record single unit activity in acute animal studies. A finite element model of planar and edge electrodes relative to neuron position reveals that edge electrodes should be beneficial for increasing the volume of tissue being sampled in recording applications.
- Published
- 2011
65. An alginate hydrogel dura mater replacement for use with intracortical electrodes
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Elizabeth A Nunamaker and Daryl R. Kipke
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musculoskeletal diseases ,Materials science ,integumentary system ,Biocompatibility ,Intracranial Pressure ,Alginates ,Sealant ,Dura mater ,Biomedical Engineering ,Biomaterial ,Soft tissue ,Biocompatible Materials ,Hydrogels ,musculoskeletal system ,Seal (mechanical) ,Biomaterials ,medicine.anatomical_structure ,Self-healing hydrogels ,medicine ,Animals ,Dura Mater ,Rabbits ,Electrodes ,Biomedical engineering ,Intracranial pressure - Abstract
The collagenous dura mater requires a secure closure following implantation of neural prosthetic devices to avoid complications due to cerebrospinal fluid leakage and infections. Alginate was previously suggested for use as a dural sealant. The liquid application and controllable gelling conditions enable alginate to conform to the unique geometries of a neural prosthetic device and the surrounding dura mater to create a barrier with the external environment. In this study, we evaluated the use of alginate as a method to securely reclose a dural defect and seal around an untethered microscale neural probe in the rabbit model. After 3 days and 3 weeks, the sealing strength of alginate remained eight times greater than normal rabbit intracranial pressure and similar in both the presence and absence of a penetrating neural probe. For time points up to 3 months, there was no significant difference in dura mater fibrosis or thickness between alginate and controls. Application of alginate to a dural defect results in a watertight seal that remains intact while the dura mater reforms. These findings indicate that alginate is an effective tool for sealing around microscale neural probes and suggests broader application as a sealant for larger neural prosthetic devices.
- Published
- 2010
66. Mechanical characterization of conducting polymer actuated neural probes under physiological settings
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Eugene D. Daneshvar, Elisabeth Smela, and Daryl R. Kipke
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Conductive polymer ,chemistry.chemical_classification ,Materials science ,Bilayer ,Nanotechnology ,Polymer ,Polypyrrole ,chemistry.chemical_compound ,chemistry ,Parylene ,Electrode ,Electroactive polymers ,Cyclic voltammetry ,Biomedical engineering - Abstract
Most implantable chronic neural probes have fixed electrode sites on the shank of the probe. Neural probe shapes and insertion methods have been shown to have considerable effects on the resulting chronic reactive tissue response that encapsulates probes. We are developing probes with controllable articulated electrode projections, which are expected to provoke less reactive tissue response due to the projections being minimally sized, as well as to permit a degree of independence from the probe shank allowing the recording sites to "float" within the brain. The objective of this study was to predict and analyze the force-generating capability of conducting polymer bilayer actuators under physiological settings. Custom parylene beams 21 μm thick, 1 cm long, and of varying widths (200 - 1000 μm) were coated with Cr/Au. Electroplated weights were fabricated at the ends of the beams to apply known forces. Polypyrrole was potentiostatically polymerized to varying thicknesses onto the Au at 0.5 V in a solution of 0.1 M pyrrole and 0.1 M dodecylbenzenesulfonate (DBS). Using cyclic voltammetry, the bilayer beams were cycled in artificial cerebrospinal fluid (aCSF) at 37 °C, as well as in aqueous NaDBS as a control. Digital images and video were analyzed to quantify the deflections. The images and the cyclic voltammograms showed that divalent cations in the aCSF interfered with polymer reduction. By integrating polypyrrole-based conducting polymer actuators, we present a type novel neural probe. We demonstrate that actuating PPy(DBS) under physiological settings is possible, and that the technique of microfabricating weights onto the actuators is a useful tool for studying actuation forces.
- Published
- 2010
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67. Investigation of the material properties of alginate for the development of hydrogel repair of dura mater
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Daryl R. Kipke, Elizabeth A Nunamaker, and Kevin J. Otto
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Materials science ,Biocompatibility ,Compressive Strength ,Alginates ,Dura mater ,Biomedical Engineering ,Context (language use) ,Biocompatible Materials ,In Vitro Techniques ,Calcium Carbonate ,Biomaterials ,Calcium Chloride ,Elastic Modulus ,Materials Testing ,medicine ,Humans ,Elastic modulus ,Syneresis ,Viscosity ,Sealant ,Hydrogels ,Biomechanical Phenomena ,Compressive strength ,medicine.anatomical_structure ,Mechanics of Materials ,Self-healing hydrogels ,Tissue Adhesives ,Dura Mater ,Rheology ,Biomedical engineering - Abstract
The collagenous dura mater isolates the brain from the external environment and requires a secure closure following invasive neurosurgery. This is typically accomplished by approximation of the dura mater via sutures and adhesives. In selected cases, however, large portions of dura mater require excision, necessitating a tissue replacement patch. The mild reaction conditions and long-term biocompatibility of alginate evince strong candidacy for these applications. This study investigates the potential of diffusion and internally gelled alginates for these applications. Specifically, we quantified the viscosity, gel rate, syneresis level, compressive strength, compressive modulus, complex modulus and loss angle in the context of dura mater repair. The ideal sealant would have a rapid cross-link speed, while the ideal dura mater replacement would have a low level of syneresis. Both applications require a compressive modulus of 20–100 kPa and a complex modulus of 1–24 kPa. The data collected in this study suggests that the use of 1.95 wt% 43 mPa s alginate with 200 mM CaCl2 is sufficient for approximating the dural membrane for closure alone or in conjunction with suture. Alternatively, the use of 1.95 wt% 43 mPa s alginate with 100 mM CaCO3 is sufficient for tissue replacement in large dural defects.
- Published
- 2010
68. Development of closed-loop neural interface technology in a rat model: combining motor cortex operant conditioning with visual cortex microstimulation
- Author
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Daryl R. Kipke, Timothy C. Marzullo, Mark J Lehmkuhle, and Gregory J. Gage
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Male ,Deep Brain Stimulation ,Biomedical Engineering ,Sensory system ,Somatosensory system ,Article ,User-Computer Interface ,Neural ensemble ,Internal Medicine ,medicine ,Microstimulation ,Animals ,Rats, Long-Evans ,Brain–computer interface ,Visual Cortex ,General Neuroscience ,Rehabilitation ,Motor Cortex ,Somatosensory Cortex ,Electric Stimulation ,Rats ,Electrophysiology ,Visual cortex ,medicine.anatomical_structure ,Brain stimulation ,Data Interpretation, Statistical ,Conditioning, Operant ,Psychology ,Neuroscience ,Microelectrodes ,Algorithms ,Motor cortex - Abstract
Closed-loop neural interface technology that combines neural ensemble decoding with simultaneous electrical microstimulation feedback is hypothesized to improve deep brain stimulation techniques, neuromotor prosthetic applications, and epilepsy treatment. Here we describe our iterative results in a rat model of a sensory and motor neurophysiological feedback control system. Three rats were chronically implanted with microelectrode arrays in both the motor and visual cortices. The rats were subsequently trained over a period of weeks to modulate their motor cortex ensemble unit activity upon delivery of intra-cortical microstimulation (ICMS) of the visual cortex in order to receive a food reward. Rats were given continuous feedback via visual cortex ICMS during the response periods that was representative of the motor cortex ensemble dynamics. Analysis revealed that the feedback provided the animals with indicators of the behavioral trials. At the hardware level, this preparation provides a tractable test model for improving the technology of closed-loop neural devices.
- Published
- 2010
69. Conduction Properties of Decellularized Nerve Biomaterials
- Author
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Ziya Baghmanli, Bong Sup Shim, Brent M. Egeland, Benjamin Wei, Paul S. Cederna, David C. Martin, Melanie G. Urbanchek, K. Schroeder, Nicholas B. Langhals, Rachel M. Miriani, and Daryl R. Kipke
- Subjects
Decellularization ,Materials science ,Nerve fascicle ,Biomaterial ,Article ,chemistry.chemical_compound ,medicine.anatomical_structure ,PEDOT:PSS ,chemistry ,Polymerization ,Ultimate tensile strength ,medicine ,Implant ,Poly(3,4-ethylenedioxythiophene) ,Biomedical engineering - Abstract
The purpose of this study is to optimize poly(3,4,- ethylenedioxythiophene) (PEDOT) polymerization into decellular nerve scaffolding for interfacing to peripheral nerves. Our ultimate aim is to permanently implant highly conductive peripheral nerve interfaces between amputee, stump, nerve fascicles and prosthetic electronics. Decellular nerve (DN) scaffolds are an FDA approved biomaterial (Axogen TM ) with the flexible tensile properties needed for successful permanent coaptation to peripheral nerves. Biocompatible, electroconductive, PEDOT facilitates electrical conduction through PEDOT coated acellular muscle. New electrochemical methods were used to polymerize various PEDOT concentrations into DN scaffolds without the need for a final dehydration step. DN scaffolds were then tested for electrical impedance and charge density. PEDOT coated DN scaffold materials were also implanted as 15-20mm peripheral nerve grafts. Measurement of in-situ nerve conduction immediately followed grafting. DN showed significant improvements in impedance for dehydrated and hydrated, DN, polymerized with moderate and low PEDOT concentrations when they were compared with DN alone (a≤ 0.05). These measurements were equivalent to those for DN with maximal PEDOT concentrations. In-situ, nerve conduction measurements demonstrated that DN alone is a poor electro-conductor while the addition of PEDOT allows DN scaffold grafts to compare favorably with the “gold standard”, autograft (Table 1). Surgical handling characteristics for conductive hydrated PEDOT DN scaffolds were rated 3 (pliable) while the dehydrated models were rated 1 (very stiff) when compared with autograft ratings of 4 (normal). Low concentrations of PEDOT on DN scaffolds provided significant increases in electro active properties which were comparable to the densest PEDOT coatings. DN pliability was closely maintained by continued hydration during PEDOT electrochemical polymerization without compromising electroconductivity.
- Published
- 2010
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70. Neural Electrodes: Interfacing Conducting Polymer Nanotubes with the Central Nervous System: Chronic Neural Recording using Poly(3,4-ethylenedioxythiophene) Nanotubes (Adv. Mater. 37/2009)
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David C. Martin, Kip A. Ludwig, Mohammad Reza Abidian, Timothy C. Marzullo, and Daryl R. Kipke
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Conductive polymer ,chemistry.chemical_compound ,Materials science ,chemistry ,Mechanics of Materials ,Interfacing ,Mechanical Engineering ,Electrode ,General Materials Science ,Nanotechnology ,Poly(3,4-ethylenedioxythiophene) - Published
- 2009
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71. The Electrocorticogram Signal Can Be Modulated With Deep Brain Stimulation of the Subthalamic Nucleus in the Hemiparkinsonian Rat
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M. J. Lehmkuhle, S. S. Bhangoo, and Daryl R. Kipke
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Male ,Deep brain stimulation ,Physiology ,medicine.medical_treatment ,Deep Brain Stimulation ,Biophysics ,Electroencephalography ,Motor Activity ,Signal ,Brain mapping ,Rats sprague dawley ,Functional Laterality ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Parkinsonian Disorders ,Subthalamic Nucleus ,medicine ,Animals ,Motor activity ,Oxidopamine ,Brain Mapping ,medicine.diagnostic_test ,Fourier Analysis ,Chemistry ,General Neuroscience ,Articles ,Electrodes, Implanted ,Rats ,Subthalamic nucleus ,Disease Models, Animal ,Neuroscience - Abstract
Electrocorticogram (ECoG) recordings of the 6-hydroxydopamine (6-OHDA)-lesioned parkinsonian rat have shown an increase in the power of cortical beta-band (15-30 Hz) oscillations ipsilateral to the lesion. The power of these oscillations is decreased with dopamine agonist administration. Here, we demonstrate that stimulation of an electrode implanted in the subthalamic nucleus alters the power of cortical beta and gamma oscillations in 6-OHDA-lesioned animals. These alterations are dependent on stimulation frequency, charge, and amplitude/pulse width. Oscillations were significantly reduced during 200- and 350-Hz stimulation. A minimum charge of 4 nC was required to elicit a reduction in oscillation power. A number of amplitude and pulse width combinations that reached 4 nC were tested; it was found that only the combinations of 33 microA/120 micros and 65 microA/60 micros significantly reduced cortical oscillations. The reduction in beta/gamma oscillation power due to deep brain stimulation (DBS) was consistent with a significant reduction in the animals' rotational behavior, a typical symptom of parkinsonism in the rat. A significant shift from high beta to low gamma was observed in the peak frequencies of ECoG recordings while animals were at rest versus walking on a treadmill. However, DBS exhibited no differential effect on oscillations between these two states. EEG recordings from rodent models of DBS may provide surrogate information about the neural signatures of Parkinson's disease relative to the efficacy of DBS.
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- 2009
72. In vivo performance of a microelectrode neural probe with integrated drug delivery
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Pratik, Rohatgi, Nicholas B, Langhals, Daryl R, Kipke, and Parag G, Patil
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Microfluidics ,Brain ,Equipment Design ,Article ,Electrodes, Implanted ,Injections ,Rats ,Electrophysiology ,Rats, Sprague-Dawley ,User-Computer Interface ,Drug Delivery Systems ,Animals ,Humans ,Microelectrodes ,Infusion Pumps - Abstract
The availability of sophisticated neural probes is a key prerequisite in the development of future brain-machine interfaces (BMIs). In this study, the authors developed and validated a neural probe design capable of simultaneous drug delivery and electrophysiology recordings in vivo. Focal drug delivery promises to extend dramatically the recording lives of neural probes, a limiting factor to clinical adoption of BMI technology.To form the multifunctional neural probe, the authors affixed a 16-channel microfabricated silicon electrode array to a fused silica catheter. Three experiments were conducted in rats to characterize the performance of the device. Experiment 1 examined cellular damage from probe insertion and the drug distribution in tissue. Experiment 2 measured the effects of saline infusions delivered through the probe on concurrent electrophysiological measurements. Experiment 3 demonstrated that a physiologically relevant amount of drug can be delivered in a controlled fashion. For these experiments, Hoechst and propidium iodide stains were used to assess insertion trauma and the tissue distribution of the infusate. Artificial CSF (aCSF) and tetrodotoxin (TTX) were injected to determine the efficacy of drug delivery.The newly developed multifunctional neural probes were successfully inserted into rat cortex and were able to deliver fluids and drugs that resulted in the expected electrophysiological and histological responses. The damage from insertion of the device into brain tissue was substantially less than the volume of drug dispersion in tissue. Electrophysiological activity, including both individual spikes as well as local field potentials, was successfully recorded with this device during real-time drug delivery. No significant changes were seen in response to delivery of aCSF as a control experiment, whereas delivery of TTX produced the expected result of suppressing all spiking activity in the vicinity of the catheter outlet.Multifunctional neural probes such as the ones developed and validated within this study have great potential to help further understand the design space and criteria for the next generation of neural probe technology. By incorporating integrated drug delivery functionality into the probes, new treatment options for neurological disorders and regenerative neural interfaces using localized and feedback-controlled delivery of drugs can be realized in the near future.
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- 2009
73. In vivo evaluation of a neural stem cell-seeded prosthesis
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S. Yandamuri, Erin K. Purcell, Daryl R. Kipke, and John P. Seymour
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Male ,Scaffold ,Polymers ,Biomedical Engineering ,Cell Count ,Xylenes ,Neuroprotection ,Article ,Cell Line ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,Mice ,In vivo ,Neurotrophic factors ,Premovement neuronal activity ,Medicine ,Animals ,Progenitor cell ,Neurons ,Cell Death ,Chemistry ,business.industry ,Stem Cells ,Brain ,Neural engineering ,Prostheses and Implants ,Immunohistochemistry ,Neural stem cell ,Rats ,medicine.anatomical_structure ,Linear Models ,Neuroglia ,Stem cell ,business ,Neuroscience ,Stem Cell Transplantation - Abstract
Neural prosthetics capable of recording or stimulating neuronal activity may restore function for patients with motor and sensory deficits resulting from injury or degenerative disease. However, overcoming inconsistent recording quality and stability in chronic applications remains a significant challenge. A likely reason for this is the reactive tissue response to the devices following implantation into the brain, which is characterized by neuronal loss and glial encapsulation. We have developed a neural stem cell-seeded probe to facilitate integration of a synthetic prosthesis with the surrounding brain tissue. We fabricated parylene devices that include an open well seeded with neural stem cells encapsulated in an alginate hydrogel scaffold. Quantitative and qualitative data describing the distribution of neuronal, glial, and progenitor cells surrounding seeded and control devices is reported over four time points spanning three months. Neuronal loss and glial encapsulation associated with cell-seeded probes were mitigated during the initial week of implantation and exacerbated by six weeks post-insertion compared to control conditions. We hypothesize that graft cells secrete neuroprotective and neurotrophic factors that effect the desired healing response early in the study, with subsequent cell death and scaffold degradation accounting for a reversal of these results later. Applications of this biohybrid technology include future long-term neural recording and sensing studies.
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- 2009
74. Flavopiridol reduces the impedance of neural prostheses in vivo without affecting recording quality
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Erin K. Purcell, Kip A. Ludwig, David E. Thompson, and Daryl R. Kipke
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Male ,medicine.medical_specialty ,Future studies ,Time Factors ,Reactive gliosis ,Statistics as Topic ,Biophysics ,Stimulation ,Biophysical Phenomena ,Antigens, CD1 ,Rats, Sprague-Dawley ,Piperidines ,In vivo ,medicine ,Electric Impedance ,Animals ,Electrical impedance ,Flavonoids ,Neurons ,Analysis of Variance ,Neural Prosthesis ,Chemistry ,General Neuroscience ,Drug administration ,Brain ,Cell cycle ,Electric Stimulation ,Growth Inhibitors ,Surgery ,Rats ,Phosphopyruvate Hydratase ,Biomedical engineering - Abstract
We hypothesized that re-entry into the cell cycle may be associated with reactive gliosis surrounding neural prostheses, and that administration of a cell cycle inhibitor (flavopiridol) at the time of surgery would reduce this effect. We investigated the effects of flavopiridol on recording quality and impedance over a 28-day time period and conducted histology at 3 and 28 days post-implantation. Flavopiridol reduced the expression of a cell cycle protein (cyclin D1) in microglia surrounding probes at the 3-day time point. Impedance at 1 kHz was decreased by drug administration across the study period compared to vehicle controls. Correlations between recording (SNR, units) and impedance metrics revealed a small, but statistically significant, inverse relationship between these variables. However, the relationship between impedance and recording quality was not sufficiently strong for flavopiridol to result in an improvement in SNR or the number of units detected. Our data indicate that flavopiridol is an effective, easily administered treatment for reducing impedance in vivo, potentially through inhibiting microglial encapsulation of implanted devices. This strategy may be useful in stimulation applications, where reduced impedance is desirable for achieving activation thresholds and prolonging the lifetime of the implanted power supply. While improvements in recording quality were not observed, a combination of flavopiridol with a second strategy which enhances neuronal signal detection may enhance these results in future studies.
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- 2009
75. Insertion of a Three Dimensional Silicon Microelectrode Assembly through a Thick Meningeal Membrane
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Daryl R. Kipke, Taneev Escamilla Mackert, Takashi D. Y. Kozai, and Nicholas B. Langhals
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Silicon ,Materials science ,chemistry.chemical_element ,Sensory system ,Human brain ,Article ,Rats ,Rats, Sprague-Dawley ,Electrophysiology ,Microelectrode ,medicine.anatomical_structure ,Membrane ,Meninges ,chemistry ,Electrode ,medicine ,Animals ,Neuroscience ,Microelectrodes ,Biomedical engineering - Abstract
There are many different needs for intraoperative mapping in both rodent as well as human situations. Whether the goal of the procedure is for epileptic mapping, removal of cancerous tissue, mapping the motor and sensory cortices, or understanding the underlying neural networks within the brain, dense three-dimensional electrode arrays are necessary. In this study, we outlined and validated thicker silicon probe designs for use in intracortical mapping applications. Multiple shank and electrode site configurations were implanted successfully through rat dura as a model for human pia, and all devices maintained the electrical functionality necessary for electrophysiological mapping applications.
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- 2009
76. Shared-stimulus driving and connectivity in groups of neurons in the dorsal cochlear nucleus
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Ben M. Clopton, Daryl R. Kipke, and David J. Anderson
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Neurons ,Physics ,Dorsal cochlear nucleus ,Guinea Pigs ,Cochlear nerve ,Stimulus (physiology) ,Sensory Systems ,Noise characterization ,Cochlear nucleus ,Electrophysiology ,medicine.anatomical_structure ,Acoustic Stimulation ,Evoked Potentials, Auditory ,Medulla oblongata ,medicine ,Animals ,Wideband ,Cochlear Nerve ,Microelectrodes ,Neuroscience - Abstract
Extracellular spike discharges were recorded from ensembles of up to five neurons simultaneously in the DCN of guinea pig using solid-state, thin-film, multichannel electrodes having up to five recording sites spanning up to 600 microns. Responses from 73 unit pairs were collected of which 54 had both units responding to pseudorandom wideband noise stimulation. Shared-stimulus driving was present in 78% (42/54) of the unit pairs and could be attributed to an overlap in their spectral sensitivities. Effective connectivity was indicated for 87% (47/54) of the unit pairs. Wideband noise proved more useful than tonebursts for investigating shared-stimulus driving and connectivity because it evoked widespread, but not overly synchronous, responses in the ensembles.
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- 1991
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77. Using a Common Average Reference to Improve Cortical Neuron Recordings From Microelectrode Arrays
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Nicholas B. Langhals, Michael D Joseph, Kip A. Ludwig, Daryl R. Kipke, Rachel M. Miriani, and David J. Anderson
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Male ,Physiology ,Cortical neuron ,Computer science ,Models, Neurological ,Action Potentials ,Context (language use) ,Electroencephalography ,Signal ,Rats, Sprague-Dawley ,Reference Values ,medicine ,Animals ,Neurons ,Communication ,Signal processing ,Analysis of Variance ,medicine.diagnostic_test ,business.industry ,General Neuroscience ,Motor Cortex ,Pattern recognition ,Signal Processing, Computer-Assisted ,Noise floor ,Markov Chains ,Electrodes, Implanted ,Rats ,Microelectrode ,Noise ,Innovative Methodology ,Artificial intelligence ,business ,Microelectrodes - Abstract
In this study, we propose and evaluate a technique known as common average referencing (CAR) to generate a more ideal reference electrode for microelectrode recordings. CAR is a computationally simple technique, and therefore amenable to both on-chip and real-time applications. CAR is commonly used in EEG, where it is necessary to identify small signal sources in very noisy recordings. To study the efficacy of common average referencing, we compared CAR to both referencing with a stainless steel bone-screw and a single microelectrode site. Data consisted of in vivo chronic recordings in anesthetized Sprague-Dawley rats drawn from prior studies, as well as previously unpublished data. By combining the data from multiple studies, we generated and analyzed one of the more comprehensive chronic neural recording datasets to date. Reference types were compared in terms of noise level, signal-to-noise ratio, and number of neurons recorded across days. Common average referencing was found to drastically outperform standard types of electrical referencing, reducing noise by >30%. As a result of the reduced noise floor, arrays referenced to a CAR yielded almost 60% more discernible neural units than traditional methods of electrical referencing. CAR should impart similar benefits to other microelectrode recording technologies—for example, chemical sensing—where similar differential recording concepts apply. In addition, we provide a mathematical justification for CAR using Gauss-Markov theorem and therefore help place the application of CAR into a theoretical context.
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- 2008
78. Advanced neurotechnologies for chronic neural interfaces: new horizons and clinical opportunities
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William Shain, Jaimie M. Henderson, Gerwin Schalk, György Buzsáki, Jamille Farraye Hetke, Eberhard E. Fetz, and Daryl R. Kipke
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Cerebral Cortex ,Neurons ,Class (computer programming) ,New horizons ,Movement Disorders ,Quantitative Biology::Neurons and Cognition ,Neuroprosthetics ,Computer science ,General Neuroscience ,Symposia and Mini-Symposia ,Computer Science::Neural and Evolutionary Computation ,Electroencephalography ,Prostheses and Implants ,Electrodes, Implanted ,Electronics, Medical ,Integrated devices ,Electrophysiology ,User-Computer Interface ,Human–computer interaction ,Neuroscience ,Evoked Potentials - Abstract
Introduction Technological advances in neural interfaces are providing increasingly more powerful “toolkits” of designs, materials, components, and integrated devices for establishing high-fidelity chronic neural interfaces. For a broad class of neuroscience studies, the primary
- Published
- 2008
79. Cytotoxic analysis of the conducting polymer PEDOT using myocytes
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Rachel M. Miriani, Mohammad Reza Abidian, and Daryl R. Kipke
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Myoblast proliferation ,Materials science ,Cell Survival ,Polymers ,Surface Properties ,Biomedical Engineering ,Biocompatible Materials ,Nanotechnology ,Biosensing Techniques ,engineering.material ,Cell Line ,Polystyrene sulfonate ,Mice ,chemistry.chemical_compound ,Coating ,PEDOT:PSS ,Materials Testing ,Cell Adhesion ,Animals ,Cell Proliferation ,Conductive polymer ,chemistry.chemical_classification ,Muscle Cells ,Cell Differentiation ,Polymer ,Bridged Bicyclo Compounds, Heterocyclic ,chemistry ,Microscopy, Electron, Scanning ,engineering ,Polystyrenes ,Chemical stability ,Biosensor - Abstract
Biosensors interact with biological systems at the surface of the sensor. Coating these sensors with electrically active polymers has been suggested to improve this interface. The electrically conducting polymer poly (3, 4 ethylenedioxythiophene) (PEDOT) enhances electrical recordings by improving conductivity while maintaining chemical stability. It also offers great flexibility in studying cell substrate interactions because of the variety of counter-ions that can be incorporated into the PEDOT matrix. To provide any true benefit in cell culture or in vivo experiments, the cytotoxicity of PEDOT must first be determined. This study evaluated the cytotoxicity of PEDOT doped with either polystyrene sulfonate (PSS) or phosphate buffered saline (PBS) ions and tested the efficacy of using the conductive PEDOT substrates for myoblast proliferation and differentiation. Results show that PEDOT/PBS and PEDOT/PSS are not cytotoxic to cells and successfully support cellular proliferation and differentiation. These results establish PEDOT as a material for cell-substrate interface studies. With biosensors being modified using the new polymer coating PEDOT, this cytotoxicity study provides evidence that PEDOT coatings will not induce a cytotoxic response when implanted in vivo.
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- 2008
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80. A 64 Channelprogrammable closed-loop deep brain stimulator with 8 channel neural amplifier and logarithmic ADC
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Hyo-Gyuem Rhew, Jongwoo Lee, Daryl R. Kipke, and Michael P. Flynn
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Logarithm ,CMOS ,Finite impulse response ,business.industry ,Preamplifier ,Computer science ,Electrical engineering ,Electronic engineering ,8-bit ,System on a chip ,business ,Digital filter ,Communication channel - Abstract
We describe a 64 channel closed-loop deep brain stimulator IC for use in research and treatment of Parkinsonpsilas disease. The system generates programmable stimulation currents and senses and filters neural activity recorded with an 8 channel preamplifier and 200 kS/s 8 bit logADC. The entire system implemented in 0.18 mum CMOS, occupies 2.67 mm2, and consumes 271 muW from a 1.8 V supply. In-vivo test data is presented.
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- 2008
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81. Implantable microelectrode arrays for simultaneous electrophysiological and neurochemical recordings
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Richard B. Brown, Daryl R. Kipke, Matthew D. Gibson, Robert K. Franklin, and Matthew D. Johnson
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Male ,Dopamine ,Action Potentials ,Neurophysiology ,Local field potential ,Striatum ,Biology ,Urethane ,Article ,Rats, Sprague-Dawley ,Neurochemical ,medicine ,Animals ,Medial forebrain bundle ,Anesthetics ,Neurons ,General Neuroscience ,Medial Forebrain Bundle ,Brain ,Neurochemistry ,Corpus Striatum ,Electric Stimulation ,Electrodes, Implanted ,Rats ,Electrophysiology ,Microelectrode ,Neuroscience ,Microelectrodes ,medicine.drug - Abstract
Implantable microfabricated microelectrode arrays represent a versatile and powerful tool to record electrophysiological activity across multiple spatial locations in the brain. Spikes and field potentials, however, correspond to only a fraction of the physiological information available at the neural interface. In urethane-anesthetized rats, microfabricated microelectrode arrays were implanted acutely for simultaneous recording of striatal local field potentials, spikes, and electrically evoked dopamine overflow on the same spatiotemporal scale. During these multi-modal recordings we observed (1) that the amperometric method used to detect dopamine did not significantly influence electrophysiological activity, (2) that electrical stimulation in the medial forebrain bundle (MFB) region resulted in electrochemically transduced dopamine transients in the striatum that were spatially heterogeneous within at least 200 microm, and (3) following MFB stimulation, dopamine levels and electrophysiological activity within the striatum exhibited similar temporal profiles. These neural probes are capable of incorporating customized microelectrode geometries and configurations, which may be useful for examining specific spatiotemporal relationships between electrical and chemical signaling in the brain.
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- 2008
82. Enhanced photoacoustic neuroimaging with gold nanorods and PEBBLEs
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Russell S. Witte, Matthew O'Donnell, Daryl R. Kipke, Kang Kim, Nicholas A. Kotov, Ashish Agarwal, W. Fan, and Raoul Kopelman
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Materials science ,business.industry ,Ultrasound ,Near-infrared spectroscopy ,Nanoparticle ,Neural engineering ,Laser ,Photobleaching ,law.invention ,Optics ,law ,Nanorod ,Molecular imaging ,business ,Biomedical engineering - Abstract
Photoacoustic (PA) imaging provides excellent optical contrast with decent penetration and high spatial resolution, making it attractive for a variety of neural applications. We evaluated optical contrast agents with high absorption in the near infrared (NIR) as potential enhancers for PA neuroimaging: optical dyes, gold nanorods (GNRs) and PEBBLEs loaded with indocyanine green. Two PA systems were developed to test these agents in excised neural tissue and in vivo mouse brain. Lobster nerves were stained with the agents for 30 minutes and placed in a hybrid nerve chamber capable of electrical stimulation and recording, optical spectroscopy and PA imaging. Contrast agents boosted the PA signal by at least 30 dB using NIR illumination from a tunable pulsed laser. Photobleaching may be a limiting factor for optical dyes-the PA signal decreased steadily with laser illumination. The second setup enabled in vivo transcranial imaging of the mouse brain. A custom clinical ultrasound scanner and a 10-MHz linear array provided near real-time images during and after an injection of 2 nM gold nanorods into the tail vein. The peak PA signal from the brain vasculature was enhanced by up to 2 dB at 710 nm. Temporal dynamics of the PA signal were also consistent with mixing of the GNRs in the blood. These studies provide a baseline for enhanced PA imaging in neural tissue. The smart contrast agents employed in this study can be further engineered for molecular targeting and controlled drug delivery with potential treatment for a myriad of neural disorders.
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- 2008
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83. Laminar analysis of movement direction information in local field potentials of the rat motor cortex
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Daryl R. Kipke, Chie Kawahara, Shani E. Ross, Timothy C. Marzullo, and Gregory J. Gage
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genetic structures ,Movement ,Models, Neurological ,Local field potential ,Laminar analysis ,Neural Pathways ,medicine ,Animals ,Computer Simulation ,Rats, Long-Evans ,Cluster analysis ,Parametric statistics ,Brain Mapping ,Movement (music) ,business.industry ,Motor Cortex ,Pattern recognition ,Neurophysiology ,Evoked Potentials, Motor ,Rats ,medicine.anatomical_structure ,Artificial intelligence ,Primary motor cortex ,Nerve Net ,business ,Psychology ,Neuroscience ,Motor cortex - Abstract
Local field potentials (LFPs) have been proposed for use in controlling neural prosthetic devices because they can provide reliable motor and sensory-related information, and can easily be recorded over long periods of time. While studies have shown that directional information about motor movements can be inferred from LFPs, it is not known at what depth these signals should be recorded from in order to maximize the amount of movement information. Towards this end, we used a directional motor task in Long Evans rats, while sampling LFPs with an electrode consisting of 16 vertical recording sites that were evenly-spaced 100μm apart. This allowed for simultaneous recording of all layers of the motor cortex. The frequency components of LFPs were then analyzed using k-means clustering to determine directional information as a function of depth. Here we report our initial findings that superficial layers (II/III) of motor cortex may provide more information about movement directions then deeper layers (V). Information analysis of LFPs was conducted using a non- parametric clustering algorithm that estimated the statistical similarity of LFP frequency components associated with leftward and rightward movements using data from all layers of the rat primary motor cortex. Our findings suggest that the superficial layers of the motor cortex may be optimal for determining the movement direction from LFPs. We also provide evidence, using current source density (CSD) analysis, that the better decoding may be due to the synaptic activity in the upper layers.
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- 2007
84. Local Drug Delivery System for Dynamic Control of Neural Environment using Parylene-Based Microelectrodes
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T. Moon, Erin K. Purcell, Daryl R. Kipke, D.S. Pellinen, and John P. Seymour
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chemistry.chemical_compound ,Microelectrode ,Materials science ,Early results ,Parylene ,chemistry ,Neural Prosthesis ,Microfluidics ,Drug delivery ,Nanotechnology ,Dynamic control ,Disease treatment ,Biomedical engineering - Abstract
Delivering drugs directly and locally to the brain tissue opens new approaches to disease treatment and improving neural interfaces. Several approaches using neural prostheses have been made to deliver drugs by bypassing the blood-brain barrier (BBB). In this study, we propose a new local drug delivery system for dynamic control of the neural environment using parylene-based microelectrodes. This polymer-based flexible microelectrode has both drug delivery and electrophysiological recording capabilities in a single probe. An in vitro model using cells found in the chronic neural probe environment provides control of independent variables and thus a useful environment to test the efficacy of delivered drugs. The in vitro model uses a combination of meningeal fibroblasts, microglia and astrocytes plated directly on the microelectrode sites. The drug delivery system utilizes two different drug delivery strategies: (1) a liquid phase drug delivery for water soluble drugs via an integrated microfluidic port, and (2) drug-embedded nanoparticle-mediated delivery for water insoluble drugs pre-loaded into a passive microfluidic port. We are currently characterizing the effects of dexamethasone (DEX) delivery on cell development using impedance spectroscopy and fluorescence microscopy. Early results show that electrode sites with plated cells on functional probes increase the impedance. This local drug delivery system provides an efficient testing protocol for therapeutic drugs intended to improve the neural interface.
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- 2007
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85. In vivo stability and biocompatibility of implanted calcium alginate disks
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Daryl R. Kipke, Erin K. Purcell, and Elizabeth A Nunamaker
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Materials science ,Calcium alginate ,Biocompatibility ,Alginates ,Diffusion ,Hexuronic Acids ,Metals and Alloys ,Biomedical Engineering ,Biocompatible Materials ,engineering.material ,Matrix (biology) ,Rats ,Biomaterials ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Rheology ,chemistry ,Coating ,Glucuronic Acid ,In vivo ,Ceramics and Composites ,engineering ,Animals ,Cell encapsulation ,Biomedical engineering - Abstract
Alginate is a commonly used biomedical hydrogel whose in vivo degradation behavior is only beginning to be understood. The use of alginate in the central nervous system is gaining popularity as an electrode coating, cell encapsulation matrix, and for duraplasty. However, it is necessary to understand how the hydrogel will behave in vivo to aid in the development of alginate for use as a neural interface material. The goal of the current study was to compare the rheological behavior of explanted alginate disks and the inflammatory response to subcutaneously implanted alginate hydrogels over a 3-month period. Specifically, the effects due to (1) in situ gelling, (2) diffusion gelling, and (3) use of a poly-l-lysine (PLL) coating were investigated. While all samples' complex moduli decreased 80% in the first day, in situ gelled alginate was more stable for the first week of implantation. The PLL coating offered some stability increases for diffusion gelled alginate, but the stability in both conditions remained significantly lower than that in in situ gelled alginate. There were no differences in biocompatibility that clearly suggested one gelation method over another. These results indicate that in situ gelation is the preferred method in neural interface applications where stability is the primary concern.
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- 2007
86. Development of Neural Interfaces for Chronic Use in Neuromotor Prosthetics
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Daryl R. Kipke, John P. Seymour, Erin K. Purcell, Timothy C. Marzullo, Gregory J. Gage, and J. Subbaroyan
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Neuromuscular stimulation ,Computer science ,Neural Prosthesis ,Human–computer interaction ,Cortical control ,Rehabilitation robotics ,Biomedical engineering ,Brain–computer interface - Abstract
This paper presents a review of our neural interface research program and provides a brief introduction to the field. We focus on three key areas which aim to minimize encapsulating tissue response to chronic neural interfaces: interface architecture, mechanical stresses, and stem cell-seeded probes. We explore these areas and present our current solutions which have led to the demonstration of cortical control of neuromotor prostheses (NMPs).
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- 2007
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87. Decoding the Direction of Movements from Interneuron and Projection Cell Populations in the Basal Ganglia
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E.L. Wilber, J.D. Berke, Daryl R. Kipke, and Gregory J. Gage
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medicine.anatomical_structure ,Neocortex ,Interneuron ,Haemodynamic response ,Basal ganglia ,medicine ,Striatum ,Neurophysiology ,Psychology ,Projection (set theory) ,Neuroscience ,Brain–computer interface - Abstract
Neuromotor prostheses (NMPs) seek to replace motor functions in paralyzed humans by controlling external devices directly from recording contacts placed within the brain (in effect, bypassing the damaged neural tissue). Studies to date have focused on cortical areas for NMP control, but deeper brain structures have also been implicated in generating motor commands. Recent studies combining non-invasive brain computer interface (BCI) experiments with functional brain imaging have revealed that the hemodynamic response related to activity of the Basal Ganglia (BG) increases significantly during BCI control. The BG has long been theorized to be involved in the selection of motor actions in the neocortex, and may be an ideal location for a discrete state NMP. In this report, we investigate the directional information contained in the firing rates of cells within the nuclei of the BG. Four Long-Evans rats performed a directional nose poke task while action potentials were recorded from 21 drivable tetrodes. Our preliminary analysis has identified 16 candidate interneurons and 8 primary cells from properties of the extracellular waveforms, and has determined the amount of directional information in each cell. Using an unsupervised classification decoder of the firing rates in the BG, we could predict the animal's movement direction correctly in >80% of the trials. We further analyzed the cell ensemble decoding and found that the proposed interneuron's directional information peaked ~100-175ms before the projection cells. The fast spiking interneurons of the striatum may be an important control source for NMPs as these cells are thought to play a large role in the selection of actions.
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- 2007
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88. Linear Electrode Depth Estimation in Rat Motor Cortex by Laminar Analysis of Ketamine-Xylazine-Induced Oscillations
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Daryl R. Kipke, E. Kim, Gregory J. Gage, Azadeh Yazdan-Shahmorad, and Timothy C. Marzullo
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Polarity reversal ,Microelectrode ,Materials science ,medicine.anatomical_structure ,Electrode ,medicine ,Laminar flow ,Neurophysiology ,Cortical column ,Neuroscience ,Voltage ,Motor cortex ,Biomedical engineering - Abstract
While the development of silicon-substrate microelectrode arrays has enabled chronic recording of single unit activity from multiple neurons simultaneously, accurate interpretation of the signals depend on the anatomical placement of the electrodes. Toward this end, this paper develops an in vivo method for identifying the placement of electrodes based on laminar analysis of ketamine-xylazien-induced field potential oscillations in rat motor cortex. The proposed method is based on finding the polarity reversal in laminar oscillations which is reported to appear in upper part of layer V in laminar High Voltage Spindles (HVSs) of rat cortical column. Analysis of histological images showed a 21 mum error in the estimate of the polarity reversal depth compared to the expected range (850-1050 mum). One out of the four rats did not undergo a phase reversal. Histology verified that the electrode was placed deeper than 1050 jim. We propose that this method can be used to determine an estimate of laminar electrodes implanted in rat motor cortex
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- 2007
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89. 'Talking Directly to the Brain: Implantable Microscale Neural Interfaces for Neuroprostheses and Neuromodulation'
- Author
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Daryl R. Kipke
- Subjects
Computer science ,Neural engineering ,Neuroscience ,Neuromodulation (medicine) ,Microscale chemistry - Published
- 2007
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90. A Direct Visual and Motor Neural Interface Demonstration in a Rat
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E. Kim, Timothy C. Marzullo, M.J. Lehmkuhle, and Daryl R. Kipke
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Visual cortex ,medicine.anatomical_structure ,medicine ,Microstimulation ,Operant conditioning ,Sensory system ,Stimulus (physiology) ,Psychology ,Reinforcement ,Neuroscience ,Brain–computer interface ,Motor cortex - Abstract
Developments of the past decades have shown it is possible to decode and extract control signals directly from the brain for use in neuromotor prosthetics. Currently, there is a push towards developing closed loop interface systems. Here we describe our early results in a rat model of a sensory/motor neurophysiological feedback control system. Traditional operant conditioning techniques historically train an animal to increase or decrease the occurrence of a behavior in response to a stimulus using various types of reinforcement. Here we demonstrate a rat performing an operant conditioning task with the modification that the rat's behavioral output and stimulus input are accessed via direct electrical connections with the brain. Our preliminary results here show a rat successfully trained to modulate the firing rates of its motor cortex in response to intra-cortical microstimulation of the visual cortex.
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- 2007
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91. Implantable Neural Interfaces for Sharks
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David J. Anderson, Jeffrey Carrier, and Daryl R. Kipke
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Nervous system ,Artificial neural network ,Sensory processing ,medicine.medical_treatment ,Interface (computing) ,chemical and pharmacologic phenomena ,Sensory system ,Biology ,Neural activity ,medicine.anatomical_structure ,Human–computer interaction ,medicine ,Neural coding ,human activities ,Neuroscience ,Brain–computer interface - Abstract
Sharks swimming in the open ocean represent impressive examples of biological underwater sensor systems. Their chemical, electrical, and acoustic senses are finely tuned to survival in a complex, dynamic, and dangerous environment. While shark behavior and physiology is gaining increasing attention by marine biologists, the shark nervous system remains largely unexplored. However, it is the nervous system that holds an important key for understanding their sensory and motor acuities, and how this translates to behavior. The primary goal of this project was to develop an innovative implantable neural interface technology that would begin to pave the way for researchers to interface with highly specific targets in the nervous system of swimming sharks to monitor (record) and stimulate (write) neural activity. This project was focused at developing leading-edge neurotechnologies, MEMS technologies, and electronics into novel implantable neural interfaces in freely swimming sharks in order to investigate neural coding associated with sensory processing and natural behavior.
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- 2007
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92. In-vivo Evaluation of Chronically Implanted Neural Microelectrode Arrays Modified with Poly (3,4-ethylenedioxythiophene) Nanotubes
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Daryl R. Kipke, Mohammad Reza Abidian, L.G. Salas, David C. Martin, Timothy C. Marzullo, and Azadeh Yazdan-Shahmorad
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Conductive polymer ,Microelectrode ,chemistry.chemical_compound ,Materials science ,PEDOT:PSS ,chemistry ,Neural Prosthesis ,Electrode ,Nanotechnology ,Electrical impedance ,Poly(3,4-ethylenedioxythiophene) ,Dielectric spectroscopy ,Biomedical engineering - Abstract
The interface between neural prostheses and neural tissue plays a significant role in the long term performance of these devices. Conducting polymers have been used to modify the electrical properties of neural microelectrodes. The objective of this study was to evaluate recording chronic neural activity of neural microelectrodes that were modified with nanofibers-templated of poly (3,4-ethylenedioxythiophene) (PEDOT) nanotubes over seven week periods using impedance spectroscopy and signal-to-noise ratio measurements. PEDOT nanotubes-coated sites were found to have lower impedance and higher signal-to-noise ratio than control site.
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- 2007
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93. The Electrocorticogram as a Feedback Control Signal for Deep Brain Stimulation of the Subthalamic Nucleus in the hemi-Parkinsonian Rat
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Daryl R. Kipke, S. S. Bhangoo, and M.J. Lehmkuhle
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Deep brain stimulation ,Parkinson's disease ,business.industry ,medicine.medical_treatment ,Stimulation ,medicine.disease ,Signal ,Dopamine agonist ,Subthalamic nucleus ,Brain stimulation ,medicine ,business ,Beta (finance) ,neoplasms ,Neuroscience ,medicine.drug - Abstract
Electrocorticogram (ECoG) recordings of the 6-OHDA lesioned rat have shown an increase in the power of beta (15-30 Hz) oscillatory frequency on the lesioned side of the brain which reduces with dopamine agonist administration. Here, we were able to demonstrate that implantation and stimulation of an electrode at certain physiologic parameters in the subthalamic nucleus was able to modify the power of the beta oscillations. By measuring ECoG recordings, a deep brain stimulation (DBS) device may be able to vary its parameters to achieve a reduction in p power similar to that seen with medication.
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- 2007
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94. Fast wave propagation in auditory cortex of an awake cat using a chronic microelectrode array
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Daryl R. Kipke, Russell S. Witte, and Patrick J. Rousche
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Wave propagation ,Computer science ,Acoustics ,media_common.quotation_subject ,Models, Neurological ,Biomedical Engineering ,Action Potentials ,Stimulus (physiology) ,Auditory cortex ,Cellular and Molecular Neuroscience ,Perception ,medicine ,Animals ,Computer Simulation ,Wakefulness ,Cochlea ,media_common ,Brain Mapping ,Multielectrode array ,Electrodes, Implanted ,Visual cortex ,medicine.anatomical_structure ,Acoustic Stimulation ,Cats ,Evoked Potentials, Auditory ,Stimulus frequency ,Female ,Nerve Net ,Microelectrodes - Abstract
We investigated fast wave propagation in auditory cortex of an alert cat using a chronically implanted microelectrode array. A custom, real-time imaging template exhibited wave dynamics within the 33-microwire array (3 mm(2)) during ten recording sessions spanning 1 month post implant. Images were based on the spatial arrangement of peri-stimulus time histograms at each recording site in response to auditory stimuli consisting of tone pips between 1 and 10 kHz at 75 dB SPL. Functional images portray stimulus-locked spiking activity and exhibit waves of excitation and inhibition that evolve during the onset, sustained and offset period of the tones. In response to 5 kHz, for example, peak excitation occurred at 27 ms after onset and again at 15 ms following tone offset. Variability of the position of the centroid of excitation during ten recording sessions reached a minimum at 31 ms post onset (sigma = 125 microm) and 18 ms post offset (sigma = 145 microm), suggesting a fine place/time representation of the stimulus in the cortex. The dynamics of these fast waves also depended on stimulus frequency, likely reflecting the tonotopicity in auditory cortex projected from the cochlea. Peak wave velocities of 0.2 m s(-1) were also consistent with those purported across horizontal layers of cat visual cortex. The fine resolution offered by microimaging may be critical for delivering optimal coding strategies used with an auditory prosthesis. Based on the initial results, future studies seek to determine the relevance of these waves to sensory perception and behavior.
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- 2007
95. Information capacity of brain machine interfaces
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Gregory J. Gage, Daryl R. Kipke, and Edward L. Ionides
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education.field_of_study ,medicine.diagnostic_test ,business.industry ,Computer science ,Population ,Pattern recognition ,Local field potential ,Brain tissue ,Neurophysiology ,Electroencephalography ,Information theory ,Signal ,medicine ,Artificial intelligence ,business ,education - Abstract
Brain Machine Interfaces (BMIs) are emerging as an important research area in clinical therapy. A large range of potential BMI control signals can be found in the brain. In increasing order of volume of brain tissue being sampled, these signal includes recordings of electric discharges from multi unit activity (MUA), summed population activity of thousands of neurons via local field potentials (LFPs), and electrical activity recorded from either the surface of the brain via electrocorticograms (ECoGs) or the surface of the scalp via electroencephalograms (EEGs). While each of these signals have been studied separately, it has been difficult to compare the potential that each signal has for general prosthetic control across studies. Information theory has been proposed as an abstract measurement to bridge this gap, however the maximum information rates of any experiment is limited by the parameters defined by that experiment (e.g. inter-trial interval length, number of targets). Here we propose a different measure of information, which we call information capacity, which measures the maximum possible information rate that a signal can provide. An advantage of measuring information capacity is that it can readily be compared between different signals and different tasks. We show how to calculate information capacity making linear Gaussian assumptions, and we discuss more general possibilities. We present a case study involving a rat BMI task involving either MUA or LFP signals.
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- 2007
96. Co-adaptive Kalman filtering in a naïve rat cortical control task
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Gregory J. Gage, Kevin J. Otto, Kip A. Ludwig, and Daryl R. Kipke
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Nervous system ,Computer science ,business.industry ,Speech recognition ,Kalman filter ,Cortical neurons ,Neurophysiology ,Task (project management) ,Adaptive filter ,medicine.anatomical_structure ,Filter (video) ,Cortical control ,medicine ,Operant conditioning ,Artificial intelligence ,business ,Brain–computer interface ,Motor cortex - Abstract
Control of prosthetic devices is possible via extra-cellular recordings from cortical neurons. Many of the current cortical control paradigms consist of analyzing the relationship between cortical activity and measured arm movements, and then using this known relationship to map cortical activity to similar prosthetic arm movements. However, measured arm movements are not feasible for amputees or patients with mobility limitations hindering their ability to perform such movements. Here we explore an alternative approach using a rat model in which subjects learn prosthesis control via an adaptive decoding filter that adjusts to the modulation patterns recorded from neurons in the motor cortex. Our methodology takes into account the ability of a subject to learn an effective response strategy in conjunction with online filter adaptation. A modified Kalman filter is demonstrated to "co-adapt" by training on past periods of significant modulation during expected prosthetic device movement. Feedback pertinent to completing the cortical task is given to aid the animal in adopting a response strategy maximizing reward. One subject was able to perform the task consistently above chance after 2 days (4 sessions) of training.
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- 2007
97. Characteristics of stapedius muscle electromyograms elicited by cochlear implant stimulation in the rat
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Ryan S. Clement and Daryl R. Kipke
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medicine.medical_specialty ,Materials science ,medicine.diagnostic_test ,Dynamic range ,medicine.medical_treatment ,Electromyography ,Audiology ,Stapedius muscle ,medicine.anatomical_structure ,Cochlear implant ,otorhinolaryngologic diseases ,medicine ,Auditory system ,sense organs ,Acoustic reflex ,Eardrum ,Cochlea - Abstract
The electrical stapedius reflex (ESR) threshold, detected by eardrum acoustic impedance change, is strongly correlated with cochlear implant recipients' behavioral comfort levels. However reports suggest acoustic impedance changes are not detectable in 30-40% of patients. The goals of this study were to develop an animal model and investigate the characteristics of the stapedius muscle electromyogram (SEMG) elicited by a cochlear implant, as an alternative measure of ESR activation. Bipolar tungsten micro wire electrodes recorded the SEMG signal from the stapedius muscle of 6 rats. The cochlea was implanted with a multichannel intracochlear electrode that delivered biphasic electrical pulses. Maximum SEMG potentials were 20-500 /spl mu/V (mean: 174 /spl mu/V) or 8-42 dB SNR (mean: 24 dB). The dynamic range of the responses that reached saturation were approximately 10 dB, with threshold inversely dependent on pulse-width and electrode separation. The electrical brainstem response (EABR) threshold was 5.6 dB lower than the ESR threshold on average, but the standard deviation was relatively high (2.4 dB), suggesting that these two signals could provide independent information for objective cochlear implant fitting. Post-operative SEMGs were recorded in several animals; including one animal for up to 63 days. The results suggest the overall feasibility of the approach for objective cochlear implant fitting.
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- 2007
98. Neural probe design for reduced tissue encapsulation in CNS
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Daryl R. Kipke and John P. Seymour
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Central Nervous System ,Male ,Neurofilament ,Materials science ,Polymers ,Central nervous system ,Biophysics ,Bioengineering ,Xylenes ,Biomaterials ,Rats, Sprague-Dawley ,Laminin ,Microscopy ,Extracellular ,medicine ,Animals ,Nerve Tissue ,Cerebral Cortex ,biology ,Immunohistochemistry ,Electrodes, Implanted ,Rats ,Fibronectin ,medicine.anatomical_structure ,Mechanics of Materials ,Cerebral cortex ,Ceramics and Composites ,biology.protein ,Microscopy, Electron, Scanning ,Immunostaining ,Biomedical engineering - Abstract
This study investigated relationships between a microscale neural probe's size and shape and its chronic reactive tissue response. Parylene-based probes were microfabricated with a thick shank (48 microm by 68 microm) and an integrated thin lateral platform (5 microm by 100 microm, either solid or one of three lattice sizes). Devices were implanted in rat cerebral cortex for 4 weeks before immunostaining for neurons, astrocytes, microglia, fibronectin, laminin, and neurofilament. While nonneuronal density (NND) generally increased and neuronal density decreased within 75 microm of a probe interface compared to unimplanted control regions, there were significant differential tissue responses within 25 microm of the platform's lateral edge compared to the shank. The NND in this region of the lateral edge was less than one-third of the corresponding region of the shank (129% and 425% increase, respectively). Moreover, neuronal density around the platform lateral edge was about one-third higher than at the shank (0.70 and 0.52 relative to control, respectively). Also, microglia reactivity and extracellular protein deposition was reduced at the lateral edge. There were no significant differences among platform designs. These results suggest that neural probe geometry is an important parameter for reducing chronic tissue encapsulation.
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- 2006
99. Optimization of Microelectrode Design for Cortical Recording Based on Thermal Noise Considerations
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Michael A. Moffitt, Daryl R. Kipke, Scott F. Lempka, Matthew D. Johnson, Cameron C. McIntyre, Kevin J. Otto, and David W. Barnett
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Silicon ,Materials science ,Finite Element Analysis ,Models, Neurological ,Biomedical Engineering ,In Vitro Techniques ,Signal ,Signal-to-noise ratio ,Electric Impedance ,Animals ,Humans ,Computer Simulation ,Single-unit recording ,Man-Machine Systems ,Electrical impedance ,Cerebral Cortex ,Signal Processing, Computer-Assisted ,Equipment Design ,Neurophysiology ,Electrodes, Implanted ,Rats ,Microelectrode ,Electrode ,Microelectrodes ,Voltage ,Biomedical engineering - Abstract
Intracortical microelectrode recordings of neural activity show great promise as control signals for neuroprosthetic applications. However, faithful, consistent recording of single unit spiking activity with chronically implanted silicon-substrate microelectrode arrays has proven difficult. Many approaches seek to enhance the long-term performance of microelectrode arrays by, for example, increasing electrode biocompatibility, decreasing electrode impedance, or improving electrode interface properties through application of small voltage pulses. The purpose of this study was to use computational models to optimize the design of microelectrodes. We coupled detailed models of the neural source signal, silicon-substrate microelectrodes, and thermal noise to define the electrode contact size that maximized the signal-to-noise ratio (SNR). Model analysis combined a multi-compartment cable model of a layer V cortical pyramidal neuron with a 3D finite element model of the head and microelectrode to define the amplitude and time course of the recorded signal. A spatially-lumped impedance model was parameterized with in vitro and in vivo spectroscopy data and used to define thermal noise as a function of electrode contact size. Our results suggest that intracortical microelectrodes with a contact size of ~380 microm2 will provide an increased SNR in vivo and improve the long-term recording capabilities of silicon-substrate microelectrode arrays.
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- 2006
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100. Neural Interface Dynamics Following Insertion of Hydrous Iridium Oxide Microelectrode Arrays
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Daryl R. Kipke, Nicholas B. Langhals, and Matthew D. Johnson
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Male ,Biomedical Engineering ,Oxide ,chemistry.chemical_element ,Striatum ,Iridium ,Electrochemistry ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,medicine ,Animals ,Humans ,Acidosis ,Chemistry ,Equipment Design ,Hydrogen-Ion Concentration ,Blood proteins ,Rats ,Electrophysiology ,Microelectrode ,Biochemistry ,Blood-Brain Barrier ,Brain Injuries ,Electrode ,Microscopy, Electron, Scanning ,Biophysics ,Nervous System Diseases ,medicine.symptom ,Microelectrodes - Abstract
� Abstract—Studies examining traumatic brain injury have suggested a 'window of opportunity' exists for therapeutic agents to mitigate edema and cellular toxicity effectively. However, successful therapy also relies on identifying the extent of blood-brain barrier disruption, which is associated with excessive extra-cellular concentrations of ions, excitatory amino acids, and serum proteins. The following study investigates the use of pH-selective hydrous iridium oxide microelectrodes to assess trauma following insertion of a neural probe. Electrochemical activation of iridium microelectrode arrays was performed in either acidic (0.5 M H2SO4) or weak basic (0.3 M Na2HPO4, pH = 8.56) solutions. Both oxides demonstrated super-Nernstian pH sensitivity (-88.5 mV/pH and -77.1 mV/pH, respectively) with little interference by other cations. Data suggest that acid-grown oxide provides better potential stability than base-grown oxide (�1 = 2.8 versus 4.9 mV over 5 hours). Implantation of these electrodes into motor cortex and dorsal striatum revealed significant acidosis during and following insertion. Variability in the spatiotemporal pH profile included micro-scale inhomogeneities along the probe shank and significant differences in the averaged pH response between successive insertions using the same depth and speed. This diagnostic technology has important implications for intervention therapies in order to more effectively treat acute surgical brain trauma.
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- 2006
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