Synaptopathy Research Uwe Andreas Hermann

Transcription

1 Potential diagnose and basic understanding of hidden hearing loss Synaptopathy Research Uwe Andreas Hermann

2 Motivation Synaptopathy is a current hot topic in the research field because it focuses on a potentially huge and previously unknown deficit that many people could be suffering from. It could be the underlying reason for some of the many cases of people with fairly normal audiograms who complain about problems understanding speech in noisy conditions. If it is possible to diagnose, it could lead to hearing aids with strikingly different amplification strategies.

3 What is Synaptopathy?

4 What is Synaptopathy? Synapses connects the auditory nerve fibers (spiral ganglion cells) to the inner hair cell. There are many fibers and thus synapses per hair cell. In mice, these synapses have been shown to die off after excessive noise exposure. Synaptopathy = what you suffer from when a great amount of your synapses has been broken. Liberman (2015), Scientific American

5 What happens to your audiogram when you listen to too loud sounds? Findings in mice The answer: Nothing (if you wait two weeks) Kujawa and Liberman (2009), J. Neuroscience Mice exposed to 100 db SPL sounds for 2 hours. Thresholds raised substantially 1 day post exposure. Thresholds returned to normal after approximately 2 weeks. This is the well known temporary threshold shift (something we likely all have experienced after e.g. a rock concert).

6 Tutorial on Diagnostics DPOAEs: Distortion-product otoacoustic emissions are generated in the cochlea in response to two tones of a given frequency and sound pressure level presented in the ear canal. DPOAEs are an objective indicator of a normally functioning cochlea. ABR (an EEG measure): A measure of the Auditory Brainstem Response gives information about both the cochlea, the synapse between the cochlea and hearing nerve, and the brainstem. The test is often used with children or others who cannot respond.

7 What happens to your hearing at speech levels when you listen to too loud sounds? Findings in mice DPOAE always returns to normal. = cochlear is functioning fine. ABRs at high frequency does not! = something between cochlea and brainstem is damaged, and it mainly affects high levels this could be the effect of synaptopathy! Kujawa and Liberman (2009), J. Neuroscience

8 And the physiological count Findings in mice Further, if you count the synaptic ribbons after exposure in these mice, their numbers do not go back to normal. = all this points to a synaptic loss. Kujawa and Liberman (2009), J. Neuroscience

9 Synaptopathy may be very common in humans also In temporal bones Makary et al. (2011) counted the number of Spiral Ganglion Cells (auditory nerves). The number decreases with age, even in ears with normal inner- and outer-hair cells counts. Normal Aged IHC IHC SGC = Spiral Ganglion Cells = Auditory nerves Makary et al. (2011), JARO

10 How does this affect the patients ability to function in the real world. With synaptopathy: The representation of speech-level sounds gets more ambiguous. In quiet this is likely not a problem. However, in noise, this could be a major problem. Maybe it can explain some of the patients we see with much larger problems with speech in noise than would be predicted form their audiogram. A visual example in quiet in noise More synaptopathy Lopez-Poveda (2014) Front. Neurosci.

11 The Oticon and Salamanca University collaboration

12 The Salamanca University and Oticon collaboration Purpose 1 Investigate whether an audiogram measured with short-duration tones can predict Synaptopathy. Neuroscience Institute, University of Salamanca Purpose 2 Investigate whether humans suffer from Synaptopathy at all.

13 Hypotheses 1. Each auditory nerve fiber functions as a stochastic sampler of the sound waveform. A spike is more likely to occur when the sound pressure is high. When there are many auditory nerve fibers the summed activity becomes deterministic. 2. Synaptopathy degrades the neural waveform representation Cochlea Inner hair cell Sound waveform Stapes Basilar membrane Auditory nerve fibers Summed activity Adapted from Dorman & Wilson (2005). Am. Scientist.

14 Hypotheses 3. For long duration tones at thresholds (a regular audiogram) even patients suffering from synaptopathy will hear something = eventually some nerve fibers will spike. 4. For short duration tones, the probability that a nerve fiber spikes, reduces significantly. 5. The difference between long- and short-duration thresholds is likely to be large for synaptopathy patients, and small for normal hearing subjects. Cochlea Inner hair cell Sound waveform Stapes Basilar membrane Auditory nerve fibers Summed activity Adapted from Dorman & Wilson (2005). Am. Scientist.

15 Hypotheses 3. For long duration tones at thresholds (a regular audiogram) even patients suffering from synaptopathy will hear something = eventually some nerve fibers will spike. 4. For short duration tones, the probability that a nerve fiber spikes, reduces significantly. 5. The difference between long- and short-duration thresholds is likely to be large for synaptopathy patients, and small for normal hearing subjects. Measure: 1. Regular audiogram 2. Short-duration audiogram

16 Summing up To diagnose synaptopathy could be a very important in future hearing aid fitting procedures. A quick diagnostic measure could be the short-duration audiogram as suggested by Marmel et al. (2015, frontiers in aging neuroscience). Salamanca University is currently collecting a lot of data. The first outcomes of the study will be presented at the ARO midwinter meeting in Baltimore February 2017.

17 What could hearing aids potentially do better for patients suffering from Synaptopathy? (the follow-up study) What not to do? Synaptopathy does not affect thresholds. Thus people do not need classic amplification in the half-gain rule inspired fashion. But what do we do then? Remove as much noise as possible = more aggressive noise reduction and directionality, also in easy conditions? Apply expansion rather than compression for the patients with mild hearing losses / normal audiometric hearing, to enhance speech contrasts? Amplify much more than what would be predicted from audiogram, to counteract the effect of undersampling?

18 Potential diagnose and basic understanding of hidden hearing loss Synaptopathy Research Uwe Andreas Hermann