The document summarizes research on neural engineering related to cochlear implants and intracortical microelectrodes. It discusses: 1) Cochlear implant research involving developing a method to fit implants using stapedius electromyography recordings in rats. 2) Chronic neural interfacing research using intracortical microelectrodes to record brain activity, the challenges of long-term recordings due to tissue encapsulation, and methods explored to address this like enzyme-aided electrode insertion. 3) The quantification of recording performance over time and correlations with electrode impedance.

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

3. COCHLEAR IMPLANT RESEARCH

5. Electric Activation with Cochlear Implant Hair Cells Auditory Nerves

6. Cochlear Electrode Array Cochlear Electrode Cochlea Auditory Nerve Cochlear Corporation’s Nucleus Electrode

7. Cochlear Implant Fitting 10 µA 1750 µA Dynamic Range C Level T Level Cochlear Implant Block Diagram 5-10dB

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. Stapedial EMG Recording in Rats Electrodes EMG Responses

12. Senior Design Team http://www.bioe.psu.edu/SeniorDesignProjects/SD2007/NTirko/home.swf Voted “Best website” Senior Design 2007

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

17. CHRONIC NEURAL INTERFACING

18. Brain-Machine Interface Pictures downloaded from: www.cyberkineticsinc.com Currently undergoing clinical trials BrainGate™ Demo Direct interface with individual neurons through implantable electrodes

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

21. Neural implants deteriorate in ability to record over time

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)

26. Electrode Assembly and Implant 1 2 Electrode Jig Microwire soldered into connector 3 Sterilization 4 Implantation

28. QUANTIFICATION: RECORDING PERFORMANCE

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*)

30. Results: Mean-Spike Waveform Samples PCA Analysis Threshold Alone Threshold w/ Corr

33. Quantifying Trends in Performance

34. INTERFACE MONITORING AND CHARACTERIZATION

37. R 2 =.024 R 2 = .067 R 2 = .017 R 2 =0.117

38. p-value <.01 p-value >.10 p-value <.01 p-value < .01

41. Future Work: Linking Histology with Performance* *in collaboration with Dr. Alistair Barber, PSU Medical Center, Hershey, PA

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)

44. ENHANCEMENT: ENZYME-AIDED ELECTRODE INSERTION

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.

46. Magnification:49000X SS = Subarachnoid Space PLC = Pial Cells UCF = Unit Collagen Fibrils CNS = Central Nervous System Main Structural Barrier – Pia Mater

47. Set-up Paralikar and Clement. IEEE Trans Biomed Eng, 2008 Stepper Motor Manipulator Load Cell Amplifier Microwire Array

48. Results from Collagenase-Aided Insertion Study

49. Chronic Recording Performance – Array Level

50. Chronic Recording Performance – Electrode Level

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)