An Auditory Cortex Site Critical to Discrimination Learning

1. An Auditory Cortex Site Critical to Discrimination Learning Adam Duvel and Mike Gabriel Neural Pattern Analysis

2. Auditory Cortical Lesions and Learning Controls, n =18 Auditory Cortical Lesions, n =17 90 80 70 60 50 % Response 40 30 20 10 0 Sessions

3. Auditory Cortex Lesions and TIA

4. Patterned Neurons Develop Patterned Neuronal Activity Bruce Wheeler with Deborah Leckband

5. 1 2 3 4 Correlated Neuronal Activityfrom Neuronal Networks

6. 40 30 % Active Electrodes 20 10 0 100 200 300 400 500 Local Cell Density (per mm2) Are Neurons in Patterns More Active? A. Patterned Networks Have Greater Activity Without Patterns: 1% ± 3% active electrodes 0.43 ± 0.35 Hz spike rate With Patterns: 16%  12% active electrodes 2.13 ± 3.0 Hz spike rate B. Activity Increases with Cell Density Random PatternedNeuron Cultures Well Patterned

7. Glia Develop More Rapidly On Patterns 8 days in culture Red –Neurofilament Green – GFAP -- Glia 14 days in culture 22 days in culture

8. Evaluation of a Binaural FMV Beamforming Algorithm in Noise Jeffery B. Larsen, Charissa R. Lansing, Robert C. Bilger, Bruce Wheeler, Sandeep Phatak, Nandini Iyer, Mike Lockwood, William O’Brien, Doug Jones, and Albert S. Feng Research supported by NIH grant #DC04840

9. INTRODUCTION A Frequency Banded Minimum Variance (FMV) algorithm has been developed Preliminary investigations with the FMV in simulation have been promising Evaluation of the FMV in a multi-source environment is needed to demonstrate its effectiveness The primary question of this study is: How much benefit from the FMV is obtained in noisy environments beyond that provided by directional microphones alone?

10. Setup of current preliminary investigation - Experiment #1 • Dependent variables • SRT in quiet and in noise with spondaic words • SRT in quiet and in noise with HINT sentences (Nilsson, Soli, & Sullivan, 1994) • Subject rated intelligibility of SIR passages (Cox & McDaniel, 1989) at a -4 dB SNR • 5 listeners w/ NH (20 - 40 years old) and 9 w/ SNHL (53 to 81 years old)

12. Setup #1 CD player * * Target * Computer Cardioid mics * * Reversed speech of four talkers speaking R-SPIN sentences at -40°, -20°, 20°, and 40° from target at 0° Real-time system Probe mic system

18. Setup of current preliminary investigation - Experiment #2 • Dependent variables • SRT in quiet and in noise with HINT sentences (Nilsson, Soli, & Sullivan, 1994) • Percent Correct of Keywords for CST Passages (Cox, Alexander, & Gilmore, 1987) at a 0 dB SNR • 5 listeners w/ SNHL (65 - 80 years old) • Use of speech-shaped cafeteria noise (Ricketts & Dhar, 1999) as jammer • Novel spacing and levels of jammers

23. CONCLUSIONS • FMV algorithm provides benefit across: • Competing signal types • Speech shaped cafeteria noise and reversed speech • ESSENTIALLY EQUAL BENEFIT IN EACH • Response Tasks • Intelligibility ratings - 50% higher for FMV than DM • Speech recognition - 36% improvement in WRS • Fixed and variable SRT measures • 6 TO 8 dB OF SRT IMPROVEMENT OVER DIRECTIONAL MICS ALONE FOR NORMAL HEARING LISTENERS • 8 TO 13 dB OF SRT IMPROVEMENT FOR LISTENERS WITH SNHL OVER DIRECTIONAL MICS ALONE DEPENDING UPON LOCATION OF JAMMERS

24. CONCLUSIONS (cont.) • Auditory Scenes • Setup #1 - jammers equal at +20º and +40º (Thanksgiving table scene) • VARIABLE SRT IMPROVEMENT OVER DIRECTIONAL MICS FOR LISTENERS WITH SNHL WAS 8 TO 11 dB • Setup #2 - Closest jammer at +20º was more intense than other three jammers at -80º, -40º, and +60º (4th of July picnic scene) • MEAN VARIABLE SRT IMPROVEMENT OVER DIRECTIONAL MICS FOR LISTENERS WITH SNHL WAS 13 dB (range of 8 to 19 dB across listeners)

25. FUTURE DIRECTIONS • Direct comparison of FMV with commercially available hearing aids with technology for listening in noise • Continued assessment of performance in different noise source configurations and reverberation times • Comparison of speech intelligibility performance with subjective measures of quality • Comparison of human performance with engineering metrics

26. Direct Evidence for Modular Binding Interactions between Cell Adhesion Molecules

27. The Structures of Many Adhesion Proteins Consist of Multiple Tandem Repeats of Similar Domains

28. How Does This Modular Architecture Impact Protein-mediated Intercellular Adhesion?

29. Cadherins Mediate Cell-Cell Adhesion in All Soft Tissue

30. • Cadherin extracellular regions comprise 5 similar domains.• Adhesion was predicted to involve only the outermost domain

31. The Surface Force Apparatus was used to Quantify the Force-Distance Profiles Between Cadherins on Opposed Surfaces

32. Force-distance measurements show that cadherin binds in any of three different, antiparallel alignments. Adhesion involves multiple domains.

33. Multiple binding interactions may facilitate the sequential assembly of tight cell-cell junctions.

35. Sequential interactions impede the abrupt failure of adhesive junctions under force.

36. Cadherin monolayers detach in an unusual way

37. Conclusions • Cadherin binds in multiple, antiparallel alignments • This is a consequence of the modular domain structure of the cadherin extracellular region • These multiple binding interactions may (1) facilitate the self-assembly of adhesive junctions and (2) impede their abrupt failure under force.