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Modeling the impact of cochlear impairment on brainstem processing

Modeling the impact of cochlear impairment on brainstem processing. Dan Goodman 1 , Alain de Cheveigné 2,3,4,5 , Christian Lorenzi 2 , Jean-Marc Edeline 3,6 , Arkadiusz Stasiak 7 , Ian Winter 7

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Modeling the impact of cochlear impairment on brainstem processing

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  1. Modeling the impact of cochlear impairment on brainstem processing Dan Goodman1, Alain de Cheveigné2,3,4,5, Christian Lorenzi2, Jean-Marc Edeline3,6, Arkadiusz Stasiak7, Ian Winter7 (1) Harvard Medical School, (2) CNRS, (3) Ecole normale supérieure, (4) Université Paris Descartes, (5) University College London, (6) Université Paris Sud, (7) University of Cambridge

  2. Motivation

  3. - cochlear hearing loss affects 5-8 million in Europe - can lead to impaired speech understanding even if thresholds close to normal - hypothesis: impairment may affect neural coding, in particular the temporal fine structure (TFS) of spike trains within auditory nerve (AN)

  4. multiple potential mechanisms - within channel: - loss of synchrony - distortion( less accurate representation of waveform) - impaired selectivity ( interference from off-CF power) - fewer fibers  degraded temporal representation - across channel: - modified BM phase characteristics  degraded cross-CF interaction - greater between-CF correlation  less information Heinz et al., 2010.

  5. likely to affect processing in CNS Primary-like: Octopus cell: synaptic conductance (nS) Golding, Oertel, J Physiol 2012 Rothman, Young, Manis, J. Neurophys., 2003

  6. our project

  7. psychophysics: - TFS & speech intelligibility physiology: - cochlear nucleus (CN) of hearing impaired guinea pigs modeling: - periphery (filtering, transduction, spike generation) - CN (primary-like, PL with notch, chopper, etc.) Strategy: - apply impairment to periphery model, - observe effect on CN model, - compare to impaired guinea pig CN responses, - interpret in relation to psychophysics & clinical data

  8. Physiology - subjects: - normal guinea pigs - noise-exposed GPs (1h @ 2 kHz, 120 dB, designed to produce loss of AN fibers with no threshold shift, Kujawa & Liberman 2009) Kujawa & Liberman, J Neurosci 2009

  9. Physiology - stimuli: pure tones, conspecific vocalizations (chirp, purr, chutter, whistle), also swith reverse polarity "guinea pig speech" Chirp Chutter Purr Whistle

  10. Physiology - extracellular recording of single units in CN main response types: actually: a continuum (Typlt et al. PLOS one, 2012)

  11. Physiology - analysis all-order interspike intervals  autocorrelation histogram ISIs between repetitions  shuffled autocorrelation histogram (SAC) Joris et al., Hearing Research, 2006

  12. in response to wideband stimulus: CF < 5 kHz, TFS CF > 5 kHz, no TFS XAC(0) /SAC(0) measures TFS relative to envelope encoding Joris et al., Hearing Research, 2006

  13. Results - impairment ~ 20 dB threshold shift 0.1-3kHz, no bandwidth widening - large variability of responses, overlap between NH and HI - nonetheless: trend observed for XAC/SAC metric in PL, PLn and LF units normal hearing: XAC / SAC XAC / SAC XAC / SAC XAC / SAC

  14. Results - impairment ~ 20 dB threshold shift 0.1-3kHz, no bandwidth widening - large variability of responses, overlap between NH and HI - nonetheless: trend observed for XAC/SAC metric in PL, PLn and LF units hearing impaired: XAC / SAC XAC / SAC XAC / SAC XAC / SAC Kale & Heinz, JARO 2010

  15. modeling

  16. Periphery: - sound  AN spike trains - reproduce normal response (tuned based on published data) - apply impairment Brainstem: - AN spike trains  CN spike trains - reproduce normal response (tuned based on NH guinea pig) - apply impairment - compare to HI guinea pig cochlea CN IC AC AN sound spikes

  17. Periphery - several models: simple linear, Zilany et al 2009 - calibrated based on published AN data

  18. Cochlear nucleus: - leaky integrate and fire, multiple AN inputs, multiple CFs, multiple delays, membrane noise, refractory period, etc. - calibrated based on measured CN data PLn, model PLn, guinea pig

  19. Model calibrated on normal GP is used to reproduce the data from the noise-exposed GP, by introducing "impairments" at various stages. - overall gain reduction in AN model - gain reduction in IHC and/or OHC path - reduction of AN fiber count

  20. Results - overall gain shift in AN model: model: guinea pig: XAC / SAC

  21. Results - reduced fiber count in PLn model: model: guinea pig:

  22. Results - impaired IHC path in Z&B model: model: guinea pig:

  23. Conclusions • model framework to study TFS impairment • calibrated based on normal responses, tested based on impaired responses • helps make sense of data from impaired guinea pig • in the future: such models should help structure our predictions about central correlates of peripheral impairment

  24. Young, in Henderson et al. 2010

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