Neural Engineering: Cochlear Implants and Intracortical Microelectrodes Ryan S. Clement, PhD Assistant Professor Departmen...
Overview of Research <ul><li>Cochlear Implant (CI) Research: </li></ul><ul><ul><li>Stapedial EMG-based cochlear implant (C...
COCHLEAR IMPLANT RESEARCH
(The University of Melbourne) Cochlear Implant Facts <ul><li>Quick Facts: </li></ul><ul><ul><li>candidacy : severe-to-prof...
Electric Activation with Cochlear Implant Hair Cells Auditory Nerves
Cochlear Electrode Array Cochlear Electrode Cochlea Auditory Nerve Cochlear Corporation’s Nucleus Electrode
Cochlear Implant Fitting 10 µA 1750 µA Dynamic   Range C Level T Level Cochlear Implant Block Diagram 5-10dB
316   A Perceived Stimulus Intensity Low High Eardrum  Cochlea Anvil Hammer Stirrup Stapedius Muscle http://www.l5media.c...
Stapedial EMG Recording in Rats Electrodes EMG Responses
 
Undergraduate Contributions <ul><li>Oneximo Gonzales </li></ul><ul><li>First student successfully trained to perform middl...
Senior Design Team http://www.bioe.psu.edu/SeniorDesignProjects/SD2007/NTirko/home.swf   Voted “Best website” Senior Desig...
The End Goal: Clinical Application Surgical view during human cochlear implant Dynamic modulation of stimulus level Cochle...
Next Steps: Future Project Ideas <ul><li>Electrode design for clinical application </li></ul><ul><ul><li>Develop prototype...
<ul><li>Integration with Cochlear Implant system </li></ul><ul><ul><li>Collaboration with Cochlear Corporation </li></ul><...
<ul><li>Basic Research Explorations </li></ul><ul><ul><li>Comparisons with…  </li></ul></ul><ul><ul><ul><li>acoustic imped...
CHRONIC NEURAL INTERFACING
Brain-Machine Interface Pictures downloaded from:  www.cyberkineticsinc.com   Currently undergoing clinical trials BrainGa...
Model-based analysis of cortical recording with silicon  Microelectrodes (Michael A. Moffitt, Cameron C. McIntyre*) Intrac...
Chronic Neural Interface Design Space <ul><li>Electrode attachment: </li></ul><ul><li>free-floating </li></ul><ul><li>fixe...
Neural implants deteriorate in ability to record over time
Chronic Recording Performance R17 Days Post Implant Average Electrode Impedance R16 R12 Number of Electrodes with Units > ...
Hypothesized Failure Mechanisms <ul><li>Tissue encapsulation (scarring) </li></ul><ul><li>Neuronal cell death </li></ul><u...
Highlights of Our Previous Research <ul><li>Quantification: </li></ul><ul><ul><li>Methods for processing signals and objec...
MICROWIRE ELECTRODES AND IMPLANTATION <ul><li>Basic Techniques: </li></ul>
Electrode Assembly and Implant 1 2 Electrode Jig Microwire soldered into connector 3 Sterilization 4 Implantation
Basic Neural Implant Procedure <ul><li>Craniotomy </li></ul><ul><li>Bone-screws </li></ul><ul><li>Electrode Insertion </li...
QUANTIFICATION:  RECORDING PERFORMANCE
Amplification/filtering, A/D conversion, digital filtering analyzed  electrode Experimental Overview: Signal Processing Co...
Results: Mean-Spike Waveform Samples PCA Analysis Threshold Alone Threshold w/ Corr
Number of Events Results: Event Detection Rates <ul><li>Use of  inter-electrode correlation  significantly reduces event c...
<ul><li>Performance Coefficients </li></ul><ul><li>To quantify the neural recordings, four performance parameters were ide...
Quantifying Trends in Performance
INTERFACE MONITORING AND CHARACTERIZATION
Undergraduate Research Highlight <ul><li>Sarah Pekny (BioE senior) </li></ul><ul><ul><li>Honor Thesis (2009) </li></ul></u...
Basic Approach <ul><li>Subjects: </li></ul><ul><li>3 Sprague Dawley rats implanted bilaterally and survived for up to 5 we...
R 2 =.024 R 2  = .067 R 2  = .017 R 2  =0.117
p-value <.01 p-value >.10 p-value <.01 p-value < .01
<ul><li>The two groups for the weekly breakdown were Day 0-Day 14 and Day 15-end (varies from 31-33 days) </li></ul><ul><l...
Conclusions <ul><li>Electrical impedance values were most strongly correlated with metrics related to the background noise...
Future Work: Linking Histology with Performance* *in collaboration with Dr. Alistair Barber, PSU Medical Center, Hershey, PA
MRI of Implanted Electrodes *In collaboration with Dr. Andrew Webb @ PSU 1 week 1 month T2 weighted images 7-tesla T2-weig...
Future Project Ideas <ul><li>Evaluate impedances between electrodes in the array </li></ul><ul><li>Obtain more histology <...
ENHANCEMENT: ENZYME-AIDED ELECTRODE INSERTION
Polymer-based Probes Polyimide Probes Active Groups : Arizona State University University of Illinois at Chicago Universit...
Magnification:49000X SS = Subarachnoid Space PLC = Pial Cells UCF = Unit Collagen Fibrils CNS = Central Nervous System Mai...
Set-up Paralikar and Clement.  IEEE Trans Biomed Eng, 2008 Stepper Motor Manipulator Load Cell Amplifier Microwire Array
Results from Collagenase-Aided Insertion Study
Chronic Recording Performance – Array Level
Chronic Recording Performance – Electrode Level
Potential Project Ideas <ul><li>Evaluate geometric factors on insertion force:  </li></ul><ul><ul><li>Electrode spacing, t...
Acknowledgements Funding : Whitaker Foundation, Penn State Department of Bioengineering, Grace-Woodward Grant, NIH NIDCD R...
Thank You <ul><li>Questions? </li></ul>
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Neural Engineering Research Overview

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Overview of research in the Neurotechnology Research Lab at Penn State

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  • Neural Engineering Research Overview

    1. 1. Neural Engineering: Cochlear Implants and Intracortical Microelectrodes Ryan S. Clement, PhD Assistant Professor Department of Bioengineering The Pennsylvania State University November 21, 2008 Western New England College
    2. 2. Overview of Research <ul><li>Cochlear Implant (CI) Research: </li></ul><ul><ul><li>Stapedial EMG-based cochlear implant (CI) fitting </li></ul></ul><ul><li>Chronic Neural Interfacing with Microelectrodes: </li></ul><ul><ul><li>Interface characterization </li></ul></ul><ul><ul><li>Exploring brain tissue response on chronic recording performance </li></ul></ul><ul><ul><li>Intervention strategies to extend recording life </li></ul></ul>
    3. 3. COCHLEAR IMPLANT RESEARCH
    4. 4. (The University of Melbourne) Cochlear Implant Facts <ul><li>Quick Facts: </li></ul><ul><ul><li>candidacy : severe-to-profound sensorineural deafness </li></ul></ul><ul><ul><li>mechanism : electrical stimulation bypasses impaired cochlea </li></ul></ul><ul><ul><li>~100,000 recipients worldwide (~21,000 in the U.S.) * </li></ul></ul><ul><ul><li>50% children (12 mo-17 years); 50% adults * </li></ul></ul><ul><ul><li>Manufacturers: </li></ul></ul><ul><ul><ul><li>Cochlear Corporation : Nucleus TM </li></ul></ul></ul><ul><ul><ul><li>Advanced Bionics : Clarion TM </li></ul></ul></ul><ul><ul><ul><li>Med-EL : Combi-40+ TM </li></ul></ul></ul><ul><ul><ul><li>AllHear : AllHear TM single channel </li></ul></ul></ul><ul><ul><ul><li>Antwerp Bionic Systems : Laura TM (now owned by Cochlear) </li></ul></ul></ul><ul><ul><ul><li>MXM Laboratories : Digisonic TM </li></ul></ul></ul>* FDA survey of venders 11/2001 http://www.nidcd.nih.gov/health/pubs_hb/coch.htm#c Cochlear Corporation: Nucleus TM FDA approved
    5. 5. Electric Activation with Cochlear Implant Hair Cells Auditory Nerves
    6. 6. Cochlear Electrode Array Cochlear Electrode Cochlea Auditory Nerve Cochlear Corporation’s Nucleus Electrode
    7. 7. Cochlear Implant Fitting 10 µA 1750 µA Dynamic Range C Level T Level Cochlear Implant Block Diagram 5-10dB
    8. 8. 316  A Perceived Stimulus Intensity Low High Eardrum Cochlea Anvil Hammer Stirrup Stapedius Muscle http://www.l5media.com 100  V 398  A 4000 pps Stimulus On 0 50 100 150 200 250 300 350 400 Time (ms)
    9. 9. Stapedial EMG Recording in Rats Electrodes EMG Responses
    10. 11. Undergraduate Contributions <ul><li>Oneximo Gonzales </li></ul><ul><li>First student successfully trained to perform middle ear surgery in rats </li></ul><ul><li>Data analysis </li></ul><ul><li>Honors Thesis </li></ul><ul><li>Pursuing graduate studies at Pitt </li></ul><ul><li>Recipient of NSF graduate fellowship (2008) </li></ul><ul><li>Tasha Tirko </li></ul><ul><li>Electrode fabrication </li></ul><ul><li>Data analysis of stimulation rate effects </li></ul><ul><li>Honors Thesis </li></ul><ul><li>Pursuing graduate studies at Johns Hopkins </li></ul>
    11. 12. Senior Design Team http://www.bioe.psu.edu/SeniorDesignProjects/SD2007/NTirko/home.swf Voted “Best website” Senior Design 2007
    12. 13. The End Goal: Clinical Application Surgical view during human cochlear implant Dynamic modulation of stimulus level Cochlea Cochlear Implant Electrode Array Stapes Stapedius Muscle
    13. 14. Next Steps: Future Project Ideas <ul><li>Electrode design for clinical application </li></ul><ul><ul><li>Develop prototype and any insertion aids </li></ul></ul><ul><ul><li>Close consultation with CI surgeon </li></ul></ul><ul><ul><li>Test and evaluate designs in human cadavers </li></ul></ul><ul><ul><li>Eventually test intraoperatively </li></ul></ul>
    14. 15. <ul><li>Integration with Cochlear Implant system </li></ul><ul><ul><li>Collaboration with Cochlear Corporation </li></ul></ul><ul><ul><li>Optimization of stEMG recording with on-board amplifier and telemetry </li></ul></ul><ul><ul><li>Device modifications to integrate stEMG electrode into clinical cochlear implant system </li></ul></ul>Next Steps: Future Project Ideas
    15. 16. <ul><li>Basic Research Explorations </li></ul><ul><ul><li>Comparisons with… </li></ul></ul><ul><ul><ul><li>acoustic impedance </li></ul></ul></ul><ul><ul><ul><li>Other objective electrophysiology measures </li></ul></ul></ul><ul><ul><li>Stimulation parameter effects </li></ul></ul>Next Steps: Future Project Ideas
    16. 17. CHRONIC NEURAL INTERFACING
    17. 18. Brain-Machine Interface Pictures downloaded from: www.cyberkineticsinc.com Currently undergoing clinical trials BrainGate™ Demo Direct interface with individual neurons through implantable electrodes
    18. 19. Model-based analysis of cortical recording with silicon Microelectrodes (Michael A. Moffitt, Cameron C. McIntyre*) Intracortical Microelectrode Recordings Univ. of Utah 0 2 4 6 8 10 12 14 16 18 20 -80 -60 -40 -20 0 20 40 60 uVolts msec
    19. 20. Chronic Neural Interface Design Space <ul><li>Electrode attachment: </li></ul><ul><li>free-floating </li></ul><ul><li>fixed </li></ul><ul><li>Fabrication Technique: </li></ul><ul><li>by hand (microwires, </li></ul><ul><li>cone electrode, etc) </li></ul><ul><li>microfabrication </li></ul><ul><ul><li>photolithography </li></ul></ul><ul><ul><li>micromachining (EDM, etc) </li></ul></ul><ul><li>Method of Insertion: </li></ul><ul><li>hand insertion </li></ul><ul><li>microdrive/device insertion </li></ul><ul><ul><li>high speed (8 m/s) </li></ul></ul><ul><ul><li>slow (100 µm/min) </li></ul></ul><ul><ul><li>intermediate </li></ul></ul><ul><li>Geometric Factors: </li></ul><ul><li>electrode tip shape </li></ul><ul><li>inter-shank spacing </li></ul><ul><li>number of shanks </li></ul><ul><li>shank widths </li></ul>Material Selection: Substrate: Metallic Silicon Ceramic Polymers Insulator: Parylene Polyimide Teflon
    20. 21. Neural implants deteriorate in ability to record over time
    21. 22. Chronic Recording Performance R17 Days Post Implant Average Electrode Impedance R16 R12 Number of Electrodes with Units > 100µV R17 R16 R12 Electrode Channel ( : channel with units >100µV)
    22. 23. Hypothesized Failure Mechanisms <ul><li>Tissue encapsulation (scarring) </li></ul><ul><li>Neuronal cell death </li></ul><ul><ul><li>Necrosis </li></ul></ul><ul><ul><li>Apoptosis </li></ul></ul>W. Shain, Wadsworth Center
    23. 24. Highlights of Our Previous Research <ul><li>Quantification: </li></ul><ul><ul><li>Methods for processing signals and objective quantification of electrode performance </li></ul></ul><ul><li>Interface monitoring and characterization: </li></ul><ul><ul><li>MRI, histology </li></ul></ul><ul><ul><li>Electrode impedance </li></ul></ul><ul><li>Enhancement: </li></ul><ul><ul><li>Enzyme-aided implant insertion study </li></ul></ul>
    24. 25. MICROWIRE ELECTRODES AND IMPLANTATION <ul><li>Basic Techniques: </li></ul>
    25. 26. Electrode Assembly and Implant 1 2 Electrode Jig Microwire soldered into connector 3 Sterilization 4 Implantation
    26. 27. Basic Neural Implant Procedure <ul><li>Craniotomy </li></ul><ul><li>Bone-screws </li></ul><ul><li>Electrode Insertion </li></ul><ul><li>Closing </li></ul><ul><li>Acrylic Headcap </li></ul><ul><li>Sutures </li></ul><ul><li>Recovery </li></ul>
    27. 28. QUANTIFICATION: RECORDING PERFORMANCE
    28. 29. Amplification/filtering, A/D conversion, digital filtering analyzed electrode Experimental Overview: Signal Processing Correlation Algorithm Mean Spike (T-PCA: Threshold+PCA ) Mean Spike (T:Threshold Only) Mean Spike (Corr) *** Mean Spike (Corr-PCA) ** Principal Component Analysis Principal Component Analysis Spike Detection * 130 0 65 Time (ms) -60 -80 40 40 3 0 Time (ms) Voltage (  V) Voltage (  V) Voltage (  V) E1 E2 E3 E4 Spike on E3 Segments on other electrodes Model-based analysis of cortical recording with silicon Microelectrodes (Michael A. Moffitt, Cameron C. McIntyre*)
    29. 30. Results: Mean-Spike Waveform Samples PCA Analysis Threshold Alone Threshold w/ Corr
    30. 31. Number of Events Results: Event Detection Rates <ul><li>Use of inter-electrode correlation significantly reduces event counts. </li></ul><ul><li>This could lessen down the load on downstream processes. </li></ul>** ** **p<0.001 Paralikar K, Rao C, Clement R . 30 th Annual International Conference of IEEE-EMBS , Vancouver, Canada. 2008 (platform presentation) Paralikar K, Rao C, Clement R . Journal of Neuroscience Methods (In Revision)
    31. 32. <ul><li>Performance Coefficients </li></ul><ul><li>To quantify the neural recordings, four performance parameters were identified and extracted from the recording session data: </li></ul><ul><ul><ul><li>Number of detected spikes (# spks) </li></ul></ul></ul><ul><ul><ul><ul><li>Decreases with neuron death and migration </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Increased background noise will decrease appearance of spikes </li></ul></ul></ul></ul><ul><ul><ul><li>Peak to Peak amplitude of mean spike (P2P) </li></ul></ul></ul><ul><ul><ul><ul><li>Reflects health of neurons (both firing rate and strength) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Affected by distance of neurons away from electrode </li></ul></ul></ul></ul><ul><ul><ul><li>Standard deviation of the background noise (noise) </li></ul></ul></ul><ul><ul><ul><ul><li>Indicative of the strength of neurons firings in the background </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Increases if it starts to include more, smaller spikes that do not cross threshold </li></ul></ul></ul></ul><ul><ul><ul><li>Signal-to-noise ratio (hSNR) = P2P/noise </li></ul></ul></ul><ul><ul><ul><ul><li>Indicates the quality of the signal </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Includes neuronal firings that do not exceed +/- 3 s.d </li></ul></ul></ul></ul>
    32. 33. Quantifying Trends in Performance
    33. 34. INTERFACE MONITORING AND CHARACTERIZATION
    34. 35. Undergraduate Research Highlight <ul><li>Sarah Pekny (BioE senior) </li></ul><ul><ul><li>Honor Thesis (2009) </li></ul></ul><ul><li>Thesis Aim: The goal of this project was to identify what relationship ( if any ) exists between neural recording performance and the corresponding electrode impedance variability. </li></ul><ul><li>Hypothesis: Electrode impedance correlates with, and is predictive of, the recording performance of the electrode. </li></ul>* She presented her work in a platform talk at BMES 2008 (St. Louis, MO)
    35. 36. Basic Approach <ul><li>Subjects: </li></ul><ul><li>3 Sprague Dawley rats implanted bilaterally and survived for up to 5 weeks </li></ul><ul><li>All procedures were approved by Penn State’s IACUC </li></ul><ul><li>Electrode Arrays: </li></ul><ul><li>Hand-fabricated microwire implants (8-channel) </li></ul><ul><li>Neural Recordings: </li></ul><ul><li>Tucker-Davis Technologies System III (500-5kHz filtering w/ 12kHz sampling) </li></ul><ul><li>Several sessions per week (5-minute blocks per array) </li></ul><ul><li>Electrode impedance: </li></ul><ul><li>Bak electrode impedance tester w/ 1kHz test signal </li></ul><ul><li>Impedance measurements of each individual electrode taken during each neural recording session </li></ul>Left : The electrodes consisted of eight 50 μ m tungsten microwires arranged in a 2X4 array with ~250um spacing maintained between the recording tips. Right: Surgical view of array being inserted into cortex, to a depth of 1 mm.
    36. 37. R 2 =.024 R 2 = .067 R 2 = .017 R 2 =0.117
    37. 38. p-value <.01 p-value >.10 p-value <.01 p-value < .01
    38. 39. <ul><li>The two groups for the weekly breakdown were Day 0-Day 14 and Day 15-end (varies from 31-33 days) </li></ul><ul><li>The population of correlation coefficients between the two groups for all electrodes was compared using a student t-test for significance </li></ul>p-value < .05 p-value <.01 p-value < .01 p-value < .01
    39. 40. Conclusions <ul><li>Electrical impedance values were most strongly correlated with metrics related to the background noise energy </li></ul><ul><ul><ul><li>The correlation was strongest during the first two weeks </li></ul></ul></ul><ul><ul><ul><li>Possibly related to the formation of the glial scar which occurs during the acute inflammatory phase. </li></ul></ul></ul><ul><ul><ul><li>Impedance values also increased during this time, further supporting this idea. </li></ul></ul></ul><ul><li>Impedance is a good indicator of the electrode interface, but not of neuronal tissue health </li></ul><ul><ul><ul><li>Indicated by the weak correlation with impedance and P2P </li></ul></ul></ul><ul><ul><ul><li>Other mechanisms including neural death or migration, affect neural performance. </li></ul></ul></ul>
    40. 41. Future Work: Linking Histology with Performance* *in collaboration with Dr. Alistair Barber, PSU Medical Center, Hershey, PA
    41. 42. MRI of Implanted Electrodes *In collaboration with Dr. Andrew Webb @ PSU 1 week 1 month T2 weighted images 7-tesla T2-weighted Analysis Paralikar K, Neuberger T, Matsui J, Webb A, Clement R. . Journal of Neural Engineering (Submitted)
    42. 43. Future Project Ideas <ul><li>Evaluate impedances between electrodes in the array </li></ul><ul><li>Obtain more histology </li></ul><ul><li>Evaluate chemical changes at the interface </li></ul><ul><li>Explore other imaging modalities </li></ul>
    43. 44. ENHANCEMENT: ENZYME-AIDED ELECTRODE INSERTION
    44. 45. Polymer-based Probes Polyimide Probes Active Groups : Arizona State University University of Illinois at Chicago University of Michigan Parylene Probes (D. Kipke) (D. Kipke) Benzocyclobutene (BCB) Probes Increased flexibility to allow better mechanical impedance matching with brain tissues  goal: reduce micromotion Conflicting mechanical requirements! Need to be stiff for insertion but flexible afterward.
    45. 46. Magnification:49000X SS = Subarachnoid Space PLC = Pial Cells UCF = Unit Collagen Fibrils CNS = Central Nervous System Main Structural Barrier – Pia Mater
    46. 47. Set-up Paralikar and Clement. IEEE Trans Biomed Eng, 2008 Stepper Motor Manipulator Load Cell Amplifier Microwire Array
    47. 48. Results from Collagenase-Aided Insertion Study
    48. 49. Chronic Recording Performance – Array Level
    49. 50. Chronic Recording Performance – Electrode Level
    50. 51. Potential Project Ideas <ul><li>Evaluate geometric factors on insertion force: </li></ul><ul><ul><li>Electrode spacing, tip shape, etc </li></ul></ul><ul><li>Insertion speed effect </li></ul><ul><li>Explore relationships between dimpling and recording performance </li></ul><ul><li>Other intervention strategies: </li></ul><ul><ul><li>Anti-inflammatory drugs </li></ul></ul><ul><ul><li>photobiomodulation </li></ul></ul>
    51. 52. Acknowledgements Funding : Whitaker Foundation, Penn State Department of Bioengineering, Grace-Woodward Grant, NIH NIDCD R21DC007227 Undergraduate Students : Jonathan Lawrence Sudharshana Seshadri Natasha Tirko Kirstin Tawse Jeremy White Oneximo Gonzales Sarah Pekny Matt Pollins Priyanka Basak Neel Gowdar *** The PSU Animal Resource Program Personnel Graduate Students : Kunal Paralikar (BioE) Lavanya Krishnan (BioE) Timothy Gilmour (EE) Chinmay Rao (EE) Dan Gilbert (BioE) Joy Matsui (BioE) Collaborators : Roger Gaumond (BioE) Andrew Webb (BioE) Thomas Neuberger (BioE) Jon Isaacson (Hershey) Alistair Barber (Hershey)
    52. 53. Thank You <ul><li>Questions? </li></ul>

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