Northwestern Professor Nina Kraus is someone for whom we have a great deal of respect, so when she editorialized that Auditory Neuropathy Spectrum Disorder (ANSD) & Central Auditory Processing Disorder be viewed under the same “biological umbrella” in her editorial titled Neural Synchrony Disorders: Opening a Biological Umbrella in The Hearing Journal, it made us sit up and take notice.
However, we strongly disagree with Prof Kraus’ position, as any further conflation beyond that which occurred when Auditory Neuropathy and Auditory Dys-synchrony were combined into Auditory Neuropathy Spectrum Disorder (ANSD) in 20081 will only further muddy the waters, especially with the parent constituency; and finally we present the case that ANSD should be again separated back into the AN & AD components, reversing the Lake Como decision from six years ago.
[Editor’s Note: Post edited January 24th, 2015 to add the reference to cochlear synaptopothy, and the references to five additional articles (references 8 through 12) — Our article on noise-induced cochlear synaptopathy (cochlear neurodegeneration) delves into much more detail on this. Edited June 19th, 2015 to add Gardner-Berry et al article (reference 13).]
The Hearing Blog is a Big Fan of Dr Kraus and the Auditory Neuroscience Lab she leads at Northwestern University, with groundbreaking R&D on how both normal hearing and hearing impaired musicians have better speech perception in noise, which we extensively featured in Hearing Aid Frequency Lowering: Not All Work Equally Well. With that in mind, it gave us pause before responding to Dr Kraus’ editorial, and we are looking forward to her reply.
Dr Kraus writes,
In the early 1980s, a young man came to my lab. His parents were deeply frustrated. Although their son was bright and precocious, he had substantial hearing problems.
He responded inconsistently to sound and exhibited large discrepancies between his excellent visual cognition and poor auditory skills. The young man had normal audiometric thresholds, yet his auditory brainstem response (ABR) was absent.
This year marks the 30th anniversary of the paper in which we presented his case, and several others, identifying the dyssynchrony disorder that is now called auditory neuropathy (AN; Laryngoscope 1984;94:400-406).
The field has come a long way since then, and we now view neuropathy as a spectrum encompassing several pathologies, including disorders of the brainstem, auditory nerve, and ribbon synapses (Brain 1996;119[pt 3]:741-753; J Basic Clin Physiol Pharmacol 2000;11:215-230).
In this editorial, I propose we extend that spectrum to include another confounding and frustrating condition that audiologists must tackle: central auditory processing disorder (APD). That is, I propose we view both conditions under the biological umbrella of neural synchrony.
INCONSISTENT NEURAL FIRING
Auditory neuropathy and auditory processing disorder are characterized by normal cochlear function, at least as evaluated by conventional tests, coupled with downstream (central) dysfunction.
Both patient groups have problems with auditory attention and excessive difficulty understanding speech when the signal is degraded or the listening environment is acoustically challenging (Nature 1997;387:176-178).
Whereas patients with AN are deaf in noise (J Assoc Res Otolaryngol 2000;1:33-45), those with APD understand speech much better, albeit abnormally.
We have investigated the neurobiology of APD, and of language-learning problems more broadly, using the auditory frequency following response (FFR), a variant of the ABR.
Like the auditory brainstem response, the FFR is generated by summed synchronous firing of brainstem nuclei. The FFR is the product of sustained phase locking to periodic sounds (Ear Hear 2010;31:302-324).
The auditory brainstem response to complex sounds (cABR) combines processing of sustained and transient acoustic features. Unlike the ABR, the frequency following response reflects the confluence of cognitive and sensory processing. (Kraus N, Nicol T. The cognitive auditory system: the role of learning in shaping the biology of the auditory system. In: Popper AN, Fay RR, eds. Perspectives on Auditory Research. Heidelberg: Springer–Verlag; 2014: 299-319.)
My lab has developed techniques to evaluate the trial-by-trial consistency of the FFR in response to speech sounds. These experiments have revealed the systematic relationship of reading and language ability with FFR consistency (J Neurosci 2013;33:3500-3504).
FFR consistency improves through early childhood (Cereb Cortex 2013; doi: 10.1093/cercor/bht311); children with auditory processing disorder may experience deviant or developmentally delayed responses.
With older age, consistency declines, again in keeping with age-related difficulties in temporal processing and speech-in-noise understanding (J Neurosci 2012;32:14156-14164).
Our findings suggest that subcortical neural synchrony exists on a continuum that tracks with auditory skills and, I believe, represents the bottleneck in a substantial number of auditory processing disorder cases.
Inconsistent neural firing in response to speech may prevent the meaningful interactions with sound that support auditory–cognitive skills and reinforce precise auditory processing.
The exact neurophysiological mechanisms underlying this spectrum of dyssynchrony remain open to question but likely include cochlear mechanics (Hearing Balance Commun 2013;11:160-167), central inhibitory processes (J Exp Biol 2008;211[pt 11]:1781-1791), and descending input from the auditory cortex (Front Neural Circuits 2013;6:114).
Certain cases of dyssynchrony are treatable. We have shown that assistive listening devices (Proc Natl Acad Sci U S A 2012;109:16731-16736) and auditory training, including music (Front Aging Neurosci 2012;4:30), language experience (Brain Lang 2014;128:34-40), and computer training (Proc Natl Acad Sci U S A 2013;110:4357-4362), improve neural synchrony and communication skills.
Our Reply To Professor Kraus:
Much confusion surrounds Auditory Neuropathy Spectrum Disorder (ANSD), previously known as auditory neuropathy/dys-synchrony (AN/AD), as starting with the consensus at the 2008 Lake Como Conference (Berlin 20081), the definition changed to encompass both AN and AD. This is especially confounding to parents of newly diagnosed infants & toddlers, as the management & treatment varies widely depending on whether it’s AN or AD, as well as the underlying cause of the lesion.
Unfortunately, Professor Kraus is incorrect when she states “Auditory neuropathy and auditory processing disorder are characterized by normal cochlear function, at least as evaluated by conventional tests…” as ANSD also encompasses lack of cochlear inner hair cells (as can occur with the DFNB9 or Conexin-26 genetic mutations), damage to the stria vascularis, and synapse misfiring (cochlear synaptopathy) at the IHC-spiral ganglion junction that can occur from age and noise exposure insults,8, 9, 10, 11, 12 as well as neuropathy of the spiral ganglion &/or of the auditory nerve itself. [In addition, although OAE’s can provide important clinical information, the presence (or lack thereof) is NOT part of the differential diagnosis for ANSD.] Essentially, ANSD encompasses measurable pathologies affecting electrical signal generation and transmission, with the site of the lesion starting at the cochlea’s inner hair cells, continuing through the signal chain mentioned above, and on to the auditory nerve terminus (ANT) at the dorsal cochlear nucleus (DCN).
What is beguiling with ANSD is that the conventional pure tone audiogram is almost meaningless (Berlin et al, 20102), with the X‘s and O‘s no more than pseudo thresholds B as the unsynchronized “sensation” perceived in the auditory cortex contains little if any actual information.C
If we take the ANT-DCN junction as the “boundary” between ANSD and CAPD, essentially we can say any signal processing that occurs in the DCN is subject to Garbage In, Garbage Out constraints: If the signal arrives in an unsynchronized, temporally distorted manner, little if any subsequent processing higher up can recover the information lost in its’ generation &/or transmission. [Anecdotal evidence with adult onset ANSD patients tends to confirm this, as when their cochlear implants were switched on, the electrical signal arriving at the DCN is instantly resynchronized, with very good speech perception right in the office. This also seems to be borne out in ANSD toddlers who receive their second CI, where their speech & language acquisition improves at a much greater rate than during the time of using just one CI. 4, 5]
When ANSD is suspected, there are specific tests 2, 3 used to screen for it, diagnose it, and isolate the site of the lesion to predict the efficacy of various treatments, notably CI’s:
• Ipsilateral stapedial (acoustic) reflex thresholds are elevated above 90dB HL or are absent6, 7; C
• Acoustic ABR (aABR) wave I (cochlear action potential) and wave V are missing when alternating high-level compression & rarefaction clicks are used, which are needed to cancel out the cochlear microphonic artifact generated when the soft outer hair cells are present;
• The electrical ABR (eABR) is used in Australia to assess the electrical transmission efficiency of the auditory nerve to predict the efficacy of CI’s prior to implant surgery13 with extreme cases of very little-to-no transmission referred for auditory brainstem implant (ABI) candidacy evaluation;
• The electrocochleogram (ECochG) is used to assess inner hair cell, synapse, and spiral ganglion integrity: Some clinics perform this test using the same “golf club” electrode placed on the round window for the eABR, repurposing it from stimulation to monitoring;
• Although not commonly used as a diagnostic tool, lack of OAE suppression occurs with ANSD.
Given the resultant confusion that occurred after the discrete auditory neuropathy and auditory dys-synchrony pathologies were conflated into the catch-all “auditory neuropathy spectrum disorder” at the 2008 Lake Como Conference, it is this author’s opinion that they be separated again, as the management and treatment will widely vary depending on the precise lesion site and underlying cause (jaundice, genetic, trauma, etc…), as this will help clarify which pathology is present, reducing confusion among professionals and especially among parents of newly diagnosed infants & toddlers, which we see all the time in the 800-member Auditory Neuropathy Spectrum Disorder group.D
It is also this author’s opinion that the conflation of ANSD and CAPD as proposed by Professor Kraus will result in further confusion with both hearing care professionals and (especially) with parents of children who have one or the other pathology.
In closing, we would be delighted if Professor Kraus would reply to our own editorial, either as a comment or as a Guest Article.
(1) Management of Individuals with Auditory Neuropathy Spectrum Disorder, by Charles Berlin PhD (2008; Lake Como Conference proceedings, where AN/AD was recast as ANSD);
(2) Multi-site diagnosis and management of 260 patients with Auditory Neuropathy-Dys-synchrony (Auditory Neuropathy Spectrum Disorder), by Berlin, Hood, Russell, Morlet et al (2010)
(3) Auditory neuropathy spectrum disorder: Evaluation and management, by Patricia Roush PhD (2008)
(4) Reverse Slope Hearing Loss group on Facebook
(5) Auditory Neuropathy Spectrum Disorder group on Facebook
(6) Acoustic Middle Ear Reflexes: Simple, Underused, and Critically Important [Note the compensation values in Table 2!]
Additional references added on January 24th, 2015:
(8) Putting the ‘Neural’ Back in Sensorineural Hearing Loss, by Sharon G Kujawa PhD; The Hearing Journal: November 2014 – Volume 67 – Issue 11 – p 8; doi: 10.1097/01.HJ.0000457006.94307.97 Mirror copy
(9) Review of Hair Cell Synapse Defects in Sensorineural Hearing Impairment, by Tobias Moser, Friederike Predoehl, and Arnold Starr (2013) Mirror copy
(10) Age-Related Cochlear Synaptopathy: An Early-Onset Contributor to Auditory Functional Decline, by Yevgeniya Sergeyenko, Kumud Lal, M Charles Liberman, and Sharon G Kujawa; The Journal of Neuroscience, 21 August 2013, 33(34): 13686-13694; doi: 10.1523/JNEUROSCI.1783-13.2013. Mirror copy
(11) Acceleration of Age-Related Hearing Loss by Early Noise Exposure: Evidence of a Misspent Youth, by Sharon G Kujawa, and M Charles Liberman; The Journal of Neuroscience, 15 February 2006; 26(7): 2115-2123; doi: 10.1523/JNEUROSCI.4985-05.2006 Mirror copy
(12) Adding Insult to Injury: Cochlear Nerve Degeneration after “Temporary” Noise-Induced Hearing Loss, by Sharon G Kujawa, and M Charles Liberman; The Journal of Neuroscience, 11 November 2009, 29(45): 14077-14085; doi: 10.1523/JNEUROSCI.2845-09.2009 Mirror copy of article | Mirror copy of Supplemental Data
Additional reference added on June 19th, 2015:
(13) Pre-operative testing of patients with neuropathy or dys-synchrony. By Kirsty Gardner-Berry, William P Gibson, and Halit Sanli, Sydney Cochlear Implant Centre. The Hearing Journal, November 2005. PDF download.
(B) This author coined the term pseudo thresholds at the Auditory Neuropathy Spectrum Disorder 2012 Conference, which describes the X‘s & O‘s jotted on the pure tone audiogram when ANSD is present;
(C) Ipsilateral acoustic reflexes can be within normal limits when the cause of the ANSD symptoms is the extremely rare Charcot-Marie-Tooth Syndrome, as pointed out by Berlin in (7) above;
(D) One of the basics of Engineering is when presented with a big, difficult problem, you break it down into smaller and smaller boxes or “modules,” solve for each module, and then assemble each of these modules into a solution for the entire big problem. This methodology is also the basic principle behind Finite Element Analysis;
(E) For a truly frightening simulation of what ANSD sounds like to the sufferer, please listen to this sequence of profound, severe, moderate, mild, and then no ANSD samples, created a few years ago at Kresge by Chuck Berlin & his crew, and vetted with several unilateral ANSD patients.
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