Hidden Hearing Injury: The Emerging Science and Military Relevance of Cochlear Synaptopathy.

INTRODUCTION The phenomenon recently described as "hidden hearing loss" was the subject of a meeting co-hosted by the Department of Defense Hearing Center of Excellence and MIT Lincoln Laboratory to consider the potential relevance of noise-related synaptopathic injury to military settings and performance, service-related injury scenarios, and military medical priorities. Participants included approximately 50 researchers and subject matter experts from academic, federal, and military laboratories. Here we present a synthesis of discussion topics and concerns, as well as specific research objectives identified to develop militarily relevant knowledge. MATERIALS AND METHODS We consider findings from studies to date that have demonstrated cochlear synaptopathy and neurodegenerative processes apparently linked to noise exposure in animal models. We explore the potential relevance of these findings to the prediction and prevention of military hearing injuries, and to comorbid injuries in the neurological domain. RESULTS Noise-induced cochlear synaptopathic injury is not detected by conventional audiometric assessment of threshold sensitivity. Animal studies suggest there may be a generous window of opportunity for intervention to mitigate or prevent cochlear neurodegenerative processes, e.g., by administration of neurotrophins or antioxidants. However, it is not yet known if the mechanisms that underlie "hidden hearing loss" also occur in human beings or, if so, how to identify them early, and how and when to intervene. CONCLUSION Neurological injuries resulting from noise exposures via the auditory system have potentially significant implications for military Service Member performance, long-term Veteran health, and noise exposure standards. Mediated via auditory pathways, such injuries have possible relationship to clinical impairments including speech perception, and may be a largely overlooked contributor to cognitive symptoms associated with other military service-related injuries such as blast exposure and brain trauma. The potential health and performance consequences of noise-induced cochlear synaptopathic injury are easily overlooked, especially if it is assumed that hearing threshold sensitivity loss is the major concern. There should be a renewed impetus to further characterize and model synaptopathic mechanisms of auditory injury; study its potential impact on human auditory function, cognition, and performance metrics of military relevance; and develop solutions for auditory protection (including noise dosimetry) and treatment if appropriate following noise or blast exposure in military scenarios. We identify specific problems, solution objectives, and research objectives. Recommended research calls for a multidisciplinary approach to address cochlear nerve synaptopathy, central (brain) dysfunction, noise exposure measurement and metrics, and clinical assessment.

[1]  Shakti K. Davis,et al.  Noise dosimetry for tactical environments , 2017, Hearing Research.

[2]  L. Roberts,et al.  Evidence that hidden hearing loss underlies amplitude modulation encoding deficits in individuals with and without tinnitus , 2017, Hearing Research.

[3]  C. Trahiotis,et al.  Behavioral manifestations of audiometrically-defined "slight" or "hidden" hearing loss revealed by measures of binaural detection. , 2016, The Journal of the Acoustical Society of America.

[4]  Christopher J. Smalt,et al.  Hidden Hearing Loss and Computational Models of the Auditory Pathway: Predicting Speech Intelligibility Decline , 2016 .

[5]  M. Liberman,et al.  Toward a Differential Diagnosis of Hidden Hearing Loss in Humans , 2016, PloS one.

[6]  D. Brungart,et al.  Speech-in-Noise Tests and Supra-threshold Auditory Evoked Potentials as Metrics for Noise Damage and Clinical Trial Outcome Measures , 2016, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[7]  Yasushi Kobayashi,et al.  Pathophysiology of the inner ear after blast injury caused by laser-induced shock wave , 2016, Scientific Reports.

[8]  E. Garne,et al.  Prescribing of Antidiabetic Medicines before, during and after Pregnancy: A Study in Seven European Regions , 2016, PloS one.

[9]  N. Kraus,et al.  Not-So-Hidden Hearing Loss , 2016 .

[10]  Hari M. Bharadwaj,et al.  Auditory Brainstem Response Latency in Noise as a Marker of Cochlear Synaptopathy , 2016, The Journal of Neuroscience.

[11]  A. Starr,et al.  Auditory neuropathy — neural and synaptic mechanisms , 2016, Nature Reviews Neurology.

[12]  Jun Qin,et al.  Auditory fatigue models for prediction of gradually developed noise induced hearing loss , 2016, 2016 IEEE-EMBS International Conference on Biomedical and Health Informatics (BHI).

[13]  M. Liberman,et al.  The middle ear muscle reflex in the diagnosis of cochlear neuropathy , 2016, Hearing Research.

[14]  M. Liberman,et al.  Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss , 2015, Hearing Research.

[15]  Deanna K Meinke,et al.  DPOAE level mapping for detecting noise-induced cochlear damage from short-duration music exposures , 2015, Noise & health.

[16]  Leslie D. Liberman,et al.  Cochlear neuropathy in human presbycusis: Confocal analysis of hidden hearing loss in post-mortem tissue , 2015, Hearing Research.

[17]  Col James Ness,et al.  The Relationship Between Hearing Acuity and Operational Performance in Dismounted Combat , 2015 .

[18]  M. Charles Liberman,et al.  Towards a Diagnosis of Cochlear Neuropathy with Envelope Following Responses , 2015, Journal of the Association for Research in Otolaryngology.

[19]  U. Lemke,et al.  Oral communication in individuals with hearing impairment—considerations regarding attentional, cognitive and social resources , 2015, Front. Psychol..

[20]  Susan E. Fulton,et al.  Mechanisms of the Hearing–Cognition Relationship , 2015, Seminars in Hearing.

[21]  J. Puel,et al.  Cochlear neuropathy in the rat exposed for a long period to moderate‐intensity noises , 2015, Journal of neuroscience research.

[22]  M. Liberman,et al.  Aging after Noise Exposure: Acceleration of Cochlear Synaptopathy in “Recovered” Ears , 2015, The Journal of Neuroscience.

[23]  M. Liberman,et al.  Immediate and Delayed Cochlear Neuropathy after Noise Exposure in Pubescent Mice , 2015, PloS one.

[24]  B. Lonsbury-Martin,et al.  Efficacy and safety of N-acetylcysteine in prevention of noise induced hearing loss: A randomized clinical trial , 2015, Hearing Research.

[25]  Hari M. Bharadwaj,et al.  Individual Differences Reveal Correlates of Hidden Hearing Deficits , 2015, The Journal of Neuroscience.

[26]  T. Wells,et al.  Hearing loss associated with US military combat deployment , 2015, Noise & health.

[27]  Zachary D. Perez,et al.  Otoacoustic-emission-based medial-olivocochlear reflex assays for humans. , 2014, The Journal of the Acoustical Society of America.

[28]  M. Liberman,et al.  Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma , 2014, eLife.

[29]  Christopher J. Plack,et al.  Perceptual Consequences of “Hidden” Hearing Loss , 2014, Trends in hearing.

[30]  Lina R. Kubli,et al.  Development of a test battery for evaluating speech perception in complex listening environments. , 2014, The Journal of the Acoustical Society of America.

[31]  Edward L. Bartlett,et al.  Age-Related Changes in the Relationship Between Auditory Brainstem Responses and Envelope-Following Responses , 2014, Journal of the Association for Research in Otolaryngology.

[32]  M. Liberman,et al.  Hot Topics—Hidden hearing loss: Permanent cochlear-nerve degeneration after temporary noise-induced threshold shift , 2014 .

[33]  Hari M. Bharadwaj,et al.  Behavioral and neural measures of auditory selective attention in blast-exposed veterans with traumatic brain injury , 2014 .

[34]  Jörg Lewald,et al.  The effect of brain lesions on sound localization in complex acoustic environments. , 2014, Brain : a journal of neurology.

[35]  Howard J Hoffman,et al.  Hearing impairment associated with depression in US adults, National Health and Nutrition Examination Survey 2005-2010. , 2014, JAMA otolaryngology-- head & neck surgery.

[36]  Michael G. Heinz,et al.  Modeling the Time-Varying and Level-Dependent Effects of the Medial Olivocochlear Reflex in Auditory Nerve Responses , 2014, Journal of the Association for Research in Otolaryngology.

[37]  John G Casali,et al.  Warfighter auditory situation awareness: Effects of augmented hearing protection/enhancement devices and TCAPS for military ground combat applications , 2014, International journal of audiology.

[38]  Hari M. Bharadwaj,et al.  Cochlear neuropathy and the coding of supra-threshold sound , 2014, Front. Syst. Neurosci..

[39]  Thomas E. Nichols,et al.  Functional connectomics from resting-state fMRI , 2013, Trends in Cognitive Sciences.

[40]  Douglas S. Brungart,et al.  The Relationship between Speech Intelligibility and Operational Performance in a Simulated Naval Command Information Center , 2013 .

[41]  M. Liberman,et al.  Age-Related Cochlear Synaptopathy: An Early-Onset Contributor to Auditory Functional Decline , 2013, The Journal of Neuroscience.

[42]  M. Liberman,et al.  Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates. , 2013, Journal of neurophysiology.

[43]  A. Starr,et al.  Review of Hair Cell Synapse Defects in Sensorineural Hearing Impairment , 2013, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[44]  J. Kelly,et al.  Polytraumatic TBI: Perspectives from Military Medicine , 2013 .

[45]  John S. Oghalai,et al.  Mechanisms of Hearing Loss after Blast Injury to the Ear , 2013, PloS one.

[46]  Wei Qiu,et al.  The value of a kurtosis metric in estimating the hazard to hearing of complex industrial noise exposures. , 2013, The Journal of the Acoustical Society of America.

[47]  Luigi Ferrucci,et al.  Hearing loss and cognitive decline in older adults: questions and answers , 2014, Aging Clinical and Experimental Research.

[48]  James W. Hall,et al.  Digital Music Exposure Reliably Induces Temporary Threshold Shift in Normal-Hearing Human Subjects , 2012, Ear and hearing.

[49]  Matthew H. Davis,et al.  Effortful Listening: The Processing of Degraded Speech Depends Critically on Attention , 2012, The Journal of Neuroscience.

[50]  R. Yuste,et al.  The Brain Activity Map Project and the Challenge of Functional Connectomics , 2012, Neuron.

[51]  Chongyu Ren,et al.  Effects of Repeated “Benign” Noise Exposures in Young CBA Mice: Shedding Light on Age-related Hearing Loss , 2012, Journal of the Association for Research in Otolaryngology.

[52]  Xiaoping Du,et al.  Antioxidant treatment reduces blast-induced cochlear damage and hearing loss , 2012, Hearing Research.

[53]  L. Ferrucci,et al.  Hearing loss and cognition in the Baltimore Longitudinal Study of Aging. , 2011, Neuropsychology.

[54]  N. Kraus,et al.  A Neural Basis of Speech-in-Noise Perception in Older Adults , 2011, Ear and hearing.

[55]  D. McAlpine,et al.  Tinnitus with a Normal Audiogram: Physiological Evidence for Hidden Hearing Loss and Computational Model , 2011, The Journal of Neuroscience.

[56]  Sharon G. Kujawa,et al.  Age-Related Primary Cochlear Neuronal Degeneration in Human Temporal Bones , 2011, Journal of the Association for Research in Otolaryngology.

[57]  K. Ohlemiller,et al.  Nutrient-enhanced diet reduces noise-induced damage to the inner ear and hearing loss. , 2011, Translational research : the journal of laboratory and clinical medicine.

[58]  H. Sebastian Seung,et al.  Neuroscience: Towards functional connectomics , 2011, Nature.

[59]  Robert Leech,et al.  Normal Adult Aging and the Contextual Influences Affecting Speech and Meaningful Sound Perception , 2010, Trends in amplification.

[60]  R. Salvi,et al.  Noise trauma impairs neurogenesis in the rat hippocampus , 2010, Neuroscience.

[61]  N. Panda,et al.  Relationship between severity of traumatic brain injury (TBI) and extent of auditory dysfunction , 2010, Brain injury.

[62]  M. Liberman,et al.  Adding Insult to Injury: Cochlear Nerve Degeneration after “Temporary” Noise-Induced Hearing Loss , 2009, The Journal of Neuroscience.

[63]  A. Wingfield,et al.  Aging, hearing acuity, and the attentional costs of effortful listening. , 2009, Psychology and aging.

[64]  Richard H. Wilson,et al.  A comparison of two word-recognition tasks in multitalker babble: Speech Recognition in Noise Test (SPRINT) and Words-in-Noise Test (WIN). , 2008, Journal of the American Academy of Audiology.

[65]  Henry L. Lew,et al.  Auditory dysfunction in traumatic brain injury. , 2007, Journal of rehabilitation research and development.

[66]  Bob Davis,et al.  Hearing loss from interrupted, intermittent, and time varying non-Gaussian noise exposure: The applicability of the equal energy hypothesis. , 2007, The Journal of the Acoustical Society of America.

[67]  Rachel A McArdle,et al.  An Evaluation of the BKB-SIN, HINT, QuickSIN, and WIN Materials on Listeners With Normal Hearing and Listeners With Hearing Loss. , 2007, Journal of speech, language, and hearing research : JSLHR.

[68]  I. Bruce,et al.  Predictions of Speech Intelligibility with a Model of the Normal and Impaired Auditory-periphery , 2007, 2007 3rd International IEEE/EMBS Conference on Neural Engineering.

[69]  L. Hughes,et al.  Free radical scavengers vitamins A, C, and E plus magnesium reduce noise trauma. , 2007, Free radical biology & medicine.

[70]  M. Liberman,et al.  Acceleration of Age-Related Hearing Loss by Early Noise Exposure: Evidence of a Misspent Youth , 2006, The Journal of Neuroscience.

[71]  R. McArdle,et al.  Speech signals used to evaluate functional status of the auditory system. , 2005, Journal of rehabilitation research and development.

[72]  Henry L. Lew,et al.  Electrophysiologic Abnormalities of Auditory and Visual Information Processing in Patients with Traumatic Brain Injury , 2004, American journal of physical medicine & rehabilitation.

[73]  Ronald Klein,et al.  The impact of hearing loss on quality of life in older adults. , 2003, The Gerontologist.

[74]  Jian Wang,et al.  Auditory plasticity and hyperactivity following cochlear damage , 2000, Hearing Research.

[75]  D. Poeppel,et al.  Towards a functional neuroanatomy of speech perception , 2000, Trends in Cognitive Sciences.

[76]  R. A. Schmiedt,et al.  Age-related loss of activity of auditory-nerve fibers. , 1996, Journal of neurophysiology.

[77]  W A Ahroon,et al.  The application of frequency and time domain kurtosis to the assessment of hazardous noise exposures. , 1994, The Journal of the Acoustical Society of America.

[78]  J T Kalb,et al.  Insights into hazard from intense impulses from a mathematical model of the ear. , 1991, The Journal of the Acoustical Society of America.

[79]  W. D. Ward The role of intermittence in PTS. , 1991, Journal of the Acoustical Society of America.

[80]  Leslie J. Peters,et al.  The Effects of Speech Intelligibility on Crew Performance in an M1A1 Tank Simulator , 1990 .

[81]  H. Schuknecht,et al.  An Experimental and Clinical Study of Deafness from Lesions of the Cochlear Nerve , 1955, The Journal of Laryngology & Otology.

[82]  S. Griest,et al.  Auditory Brainstem Response Altered in Humans With Noise Exposure Despite Normal Outer Hair Cell Function , 2017, Ear and hearing.

[83]  T. Chisolm,et al.  Auditory difficulties in blast-exposed Veterans with clinically normal hearing. , 2015, Journal of rehabilitation research and development.

[84]  Bridget M Smith,et al.  Audiological issues and hearing loss among Veterans with mild traumatic brain injury. , 2012, Journal of rehabilitation research and development.

[85]  C. L. Prell,et al.  Noise-induced hearing loss: from animal models to human trials. , 2012 .

[86]  Lina R. Kubli,et al.  Implications of blast exposure for central auditory function: a review. , 2012, Journal of rehabilitation research and development.

[87]  Frederick J. Gallun,et al.  Auditory and vestibular dysfunction associated with blast-related traumatic brain injury. , 2009, Journal of rehabilitation research and development.

[88]  William A Ahroon,et al.  A field investigation of hearing protection and hearing enhancement in one device: for soldiers whose ears and lives depend upon it. , 2009, Noise & health.

[89]  S. Hébert,et al.  Salivary cortisol levels, subjective stress, and tinnitus intensity in tinnitus sufferers during noise exposure in the laboratory. , 2009, International journal of hygiene and environmental health.

[90]  Richard H Wilson,et al.  Auditory Test No . 6 in multi-talker babble : A preliminary report , 2002 .

[91]  M. Reite,et al.  Attention and memory dysfunction after traumatic brain injury: cholinergic mechanisms, sensory gating, and a hypothesis for further investigation. , 1999, Brain injury.