Research Roundup updates HR readers on some of the latest research and clinical findings related to hearing health care. Where appropriate, sources and original citations are provided, and readers are encouraged to refer to the primary literature for more detailed information. Additionally, related articles can be found and keywords can be searched in the HR Online Archives.

New Find Turns Back the Clock on Hearing: First Modern Ears Discovered on 260-Million-Year-Old Reptile

The discovery of the first anatomically modern ear in a group of 260-million-year-old fossil reptiles significantly pushes back the date of the origin of an advanced sense of hearing, and suggests the first known adaptations to living in the dark.

In a new study published in PLoS ONE (Public Library of Science), Johannes Müller and Linda Tsuji, paleobiologists at the Natural History Museum of the Humboldt University in Berlin, Germany, report that these fossil animals, found in deposits of Permian age near the Mezen River in central Russia, possessed all the anatomical features typical of a vertebrate with a surprisingly modern ear.

The ability of modern animals to hear a wide range of frequencies—highly important for prey capture, escape, and communication—was long assumed to have only evolved shortly before the origin of dinosaurs, not much longer than 200 million years ago, and therefore comparatively late in vertebrate history.

But these fossils demonstrate that this advanced ear was in existence much earlier than previously suggested. In these small reptiles, the outside of the cheek was covered with a large eardrum, and a bone comparable to our own hearing ossicles connected this structure with the inner ear and the brain. Müller and Tsuji also examined the functional performance of this unique and unexpected auditory arrangement, and discovered that these little reptiles were able to hear at least as well as a modern lizard.

NIDCD Resarch Sheds New Light on Language Evolution. September 2006 HR Insider.

But why would these animals have possessed such an ear? “Of course, this question cannot be answered with certainty,” says Müller, “but when we compared these fossils with modern land vertebrates, we recognized that animals with an excellent sense of hearing, such as cats, owls, or geckos, are all active at night or under low-light conditions. And maybe this is what these Permian reptiles did too.”

The discovery of an ear comparable to modern-day standards in such ancient land vertebrates provides an entirely new piece of information about the earliest terrestrial ecosystems, which no longer seem to be as primitive as once assumed. Already by this time, there must have been intense pressure to exploit new ecological niches and to evolve new structures to gain an advantage over other species in an increasingly crowded world. At last, it was those pressures and evolutionary inventions that paved the way for our modern day environments. Source: American Association for the Advancement of Science

Original Article

Müller J, Tsuji LA. Impedance-matching hearing in Paleozoic reptiles: evidence of advanced sensory perception at an early state of Amniote evolution. Available at: www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pone.0000889. Accessed September 25, 2007.

Mild HL Impacts Long-term Neurological Processes

Mild-to-moderate forms of hearing loss can have a lasting impact on the auditory cortex, according to findings by researchers at New York University’s Center for Neural Science. The study, which is the first to show central effects of mild hearing loss, appears in the August 31, 2007 edition of the Journal of Neuroscience.

The study was authored by NYU scientists Han Xu, Vibhakar Kotak, and Dan Sanes, working in NYU’s Center for Neural Science.

Previously, researchers had been unable to conclusively determine the neurological impact of mild forms of hearing loss, which occurs when the pathway by which sound reaches the cochlea is disrupted—such as is experienced with middle ear infections during childhood. The NYU study sought to address this question in an animal model by measuring the impact of conductive hearing loss without injury to the cochlea.

The researchers induced hearing loss in the subjects during early development, then measured the functionality of neural connections within the subjects’ auditory cortex, which processes all acoustic cues.

The results showed that the projection to auditory cortex had changed following a brief period of hearing loss. Specifically, the researchers found that the synaptic response of the auditory neurons adapted more rapidly and to a greater extent. They also found that auditory cortex neurons became more sensitive to stimulation.

These findings indicate that auditory cortex function is susceptible to relatively modest levels of hearing loss during development and suggest that perceptual deficits may be linked to alterations in the central nervous system. Source: NYU.

Original Citation

Xu H, Kotak YC, Sanes DH. Conductive hearing loss disrupts synaptic and spike adaptation in developing auditory cortex. J Neuroscience. 2007;27(35):9417-9426.

Mystery of Mammalian Hair Cells and Amplification Solved?

A 30-year scientific debate over how specialized cells in the inner ear amplify sound in mammals appears to have been settled more in favor of bouncing cell bodies rather than vibrating, hair-like cilia, according to investigators at St. Jude Children’s Research Hospital.

The finding could explain why dogs, cats, humans, and other mammals have such sensitive hearing and the ability to discriminate among frequencies. The work also highlights the importance of basic hearing research in studies into the causes of deafness. A report on this work appears in the July 24 edition of Proceedings of the National Academy of Sciences.

“Our discovery helps explain the mechanics of hearing and what might be going wrong in some forms of deafness,” says Jian Zuo, PhD, the paper’s senior author and associate member of the St. Jude Department of Developmental Neurobiology. “There are a variety of causes for hearing loss, including side effects of chemotherapy for cancer. One strength of St. Jude is that researchers have the ability to ask some very basic questions about how the body works, and then use those answers to solve medical problems in the future.”

The long-standing argument centers around outer hair cells, the rod-shaped cells that respond to sound waves. Located in the fluid-filled cochlea, outer hair cells sport tufts of hair-like cilia that project into the fluid. The presence of outer hair cells makes mammalian hearing more than 100 times better than it would be if the cells were absent.

In mammals, the rod-shaped body of the outer hair cell contracts and then vibrates in response to the sound waves, amplifying the sound. In a previous study, Zuo and his colleagues showed that the protein called prestin is the motor in mammalian outer hair cells that triggers this contraction. And that is where the debate begins.

While both mammals and nonmammals have cilia on their outer hair cells, only mammalian outer hair cells have prestin, which drives this cellular contraction, or somatic motility. The contraction pulls the tufts of cilia downward, which maximizes the force of their vibration. In mammals, both the cilia and the cell itself vibrate. Thus far, the question has been whether the cilia are the main engine of sound amplification in both mammals and nonmammals.

One group of scientists believes that somatic motility in mammalian outer hair cells is simply a way to change the height of the cilia in the fluid to maximize the force with which the cilia oscillate. That, in turn, would amplify the sound. An opposing group of scientists maintains that, although the vibration of the outer hair cell body itself (somatic motility) does maximize the vibration of the cilia, the cell body works independently of its cilia. That is, vibration of the mammalian cell dominates the work of amplifying sound in mammals.

“If somatic motility is the dominant force for amplifying sound in mammals, this would mean that prestin is the reason mammals amplify sound so efficiently,” Zuo said.

In the current study, Zuo and his team conducted a complex series of studies that showed in mammals that the role of somatic mobility driven by prestin is not simply to modify the response of the outer hair cells’ cilia to incoming sound waves in the cochlea fluid. Instead, somatic motility itself appears to dominate the amplification process in the mammalian cochlea, while the cilia dominate amplification in nonmammals.

Zuo’s team took advantage of a previously discovered mutated form of prestin that does not make the outer hair cells contract in response to incoming sound waves as normal prestin does. Instead, the mutated form of prestin makes the cell extend itself when it vibrates.

The St. Jude researchers reasoned that, if altering the position of the cilia in the fluid changes the ability of the cilia to amplify sound, then hearing should be affected when the mutant prestin made the cell extend itself. Therefore, the team developed a line of genetically modified mice that carried only mutant prestin in their outer hair cells. The researchers then tested the animals’ responses to sound.

Results of the studies showed no alteration in hearing, which suggested that it did not matter whether the outer hair cells contracted or extended itself (ie, raised or lowered the cilia). There was no effect on amplification. The researchers concluded that somatic motility was not simply a way to make cilia do their job better; rather, there is no connection between the hair cell contractions and how the cilia do their job. Instead, somatic motility, generated by prestin, is the key to the superior hearing of mammals.

Other authors include Jiangang Gao, Xudong Wu, and Manish Patel (St. Jude); Xiang Wang, Shuping Jia, and David He (Creighton University, Omaha, Neb); Sal Aguinaga, Kristin Huynh, Keiji Matsuda, Jing Zheng, MaryAnn Cheatham, and Peter Dallos (Northwestern University, Evanston, Ill). The work was supported in part by ALSAC, The Hugh Knowles Center, and the National Institutes of Health. Source: St. Jude Children’s Research Hospital

Original Article

Gao J, Wang X, Wu X, et al. Prestin-based outer hair cell electromotility in knockin mice does not appear to adjust the operating point of a cilia-based amplifier. Proc Nat Acad Sci. 2007;104(30):12542-12547.

Makeover: New Tests for Hearing Loss Assessment

A Purdue University researcher is working on a new technique to diagnose hearing loss in a way that more accurately reflects real-world situations. “The traditional way to assess speech understanding in people with hearing loss is to put them in a quiet room and ask them to repeat words produced by one person they can’t see,” says Karen Iler Kirk, PhD, a professor of speech, language, and hearing sciences. “The goal of our research is to develop new tests that reflect more natural listening situations with visual cues, different background noises, voice quality, dialects, and speaking rates. This is a more accurate way to predict how people perceive speech in the real world and, therefore, can help us determine appropriate therapy and interventions, such as cochlear implants. The better the diagnostic tool we have to make such decisions, the better we can serve our patients.”

Kirk received a $2.8 million grant from the National Institute on Deafness and Other Communication Disorders (NIDCD) for the 5-year project to develop two new audiovisual and multi-talker sentence tests that expand upon the traditional spoken word recognition format that has been used since the 1950s. One test is for adults and the other for children. More than 1,000 people ages 4-65 will participate in the study.

The project will be helpful for both hearing aid and cochlear implant assessment, and also is expanding word lists from the traditional monosyllabic words to a greater range of words based on how often they are used and lexical density—the number of words phonetically similar to the target.

The 10 diverse speakers, who are recording more than 6,000 sentences combined, will not be producing perfectly articulated speech. “It’s important to use sentence materials that are produced by different speakers because in the real world, we do not listen to just one person,” Kirk says.

In addition to the auditory component, the materials will be presented in a visual format so listeners can see and hear the phrase. “This is really important because hearing-impaired people often have great difficulty understanding speech if they are just listening,” she says. “Seeing the face and following lip reading cues can help someone understand the intended message.”

Participants will be tested in auditory-only, visual-only, or auditory-plus-visual modalities. At the end of the project, DVDs containing the test, as well as instruction booklets, data-gathering forms and a manual for data interpretation, will be available to professionals. Another benefit from this study will be the raw data generated. “Just collecting information from 1,000 individuals and measuring how well they perform on these tests gives us tremendous information that is not available elsewhere,” Kirk says.

Kirk is collaborating with Brian French of Purdue, as well as Laurie Eisenberg and Arthur Boothroyd at the House Ear Institute; David Pisoni at Indiana University; and Dr. Nancy Young at Children’s Memorial Hospital in Chicago. Recruitment for participants will begin in 2008 at these various sites.

“Holy Grail” of Hair Cell Anatomy: Identity of Hair Cell Tip Links Revealed

In a study published in the September 6 issue of Nature, researchers have shed new light on the hearing process by identifying two key proteins that join together at the precise location where energy of motion is turned into electrical impulses. The discovery, described by some scientists as one of the holy grails of the field, was made by researchers at the National Institute on Deafness and Other Communication Disorders (NIDCD) and the Scripps Research Institute in La Jolla, Calif.

When a noise occurs, vibrations from the middle ear set fluid in the inner ear, or cochlea, into motion and a traveling wave to form along a membrane running down its length. Hair cells, sitting atop the membrane, “ride the wave” and bump up against an overlying membrane. When this happens, bristly structures protruding from their tops (stereocilia) tilt to one side. This tilting causes pore-sized channels to open up, ions to rush in, and an electrical signal to be generated that travels to the brain, a process called mechanoelectrical transduction.

Most scientists believe that the channel gates are opened and closed by microscopic bridges—called “tip links”—that connect shorter stereocilia to taller ones positioned behind them. If scientists could determine what the tip links are made of, they would be one step closer to understanding what causes the channel gates to open. This is no easy feat, however, because stereocilia are extremely small, scarce, and difficult to handle. Several proteins had been reported to occur at the tip link in earlier studies, but results have been conflicting to this point.

Cadherin 23 and Protocadherin 15 unite to form tip link. Using three lines of evidence, NIDCD scientists Hirofumi Sakaguchi, MD, PhD, Joshua Tokita, and Bechara Kachar, MD, together with Piotr Kazmierczak and Ulrich Müller, PhD, of Scripps Research Institute, and other collaborators have demonstrated that two proteins associated with hearing loss—cadherin 23 (CDH23) and protocadherin 15 (PCDH15)—unite and adhere to one another to form the tip link. Mutations in CDH23 are known to cause one form of Usher syndrome as well as a nonsyndromic recessive form of deafness, and mutations in PCDH15 are responsible for another form of Usher syndrome. Usher syndrome is the most common cause of deaf-blindness in humans.

“Cadherin 23 and protocadherin 15 have been implicated in a variety of forms of late- and early-onset deafness, and a whole range of mutations can produce different outcomes,” says NIDCD’s Kachar, a co-senior investigator on the study. “Now that we know how these two proteins interact at the tip link, we can perhaps predict how different types of hearing loss can take place depending on where a mutation is located.”

Three lines of evidence. The researchers first created antibodies that would bind to and label short segments on the CDH23 and PCDH15 proteins in the inner ears of rats and guinea pigs. (Both proteins were identified at the tip link, respectively, in earlier studies.) Using green fluorescence and electron microscopy studies, they showed that CDH23 was located on the side of the taller stereocilium and PCDH15 was present on the tip of the shorter one, with their loose ends overlapping in between. The researchers were able to identify both proteins, while earlier studies had not, because they removed an obstacle to the antibody-binding process: calcium. Under normal conditions, CDH23 and PCDH15 are studded with calcium ions, which prevent antibodies from binding to the targeted sites. When calcium was removed through the addition of a chemical known as BAPTA, both labels became visible.

Next, the researchers built a structure resembling a tip link by expressing the CDH23 and PCDH15 proteins in the laboratory and watching how they interacted. When conditions were right, the two proteins wound themselves tightly together from one end to the other in a configuration that mirrored a naturally occurring tip link. The results were surprising, since the scientific consensus had been that these proteins would not interact at all. As with normal tip links, the structure thrived in calcium concentrations that paralleled those found in fluid of the inner ear, while a drastic reduction in calcium disrupted the structure.

Lastly, the scientists found that one mutation of PCDH15 that causes one form of deafness inhibited the interaction of the two proteins, leading them to conclude that the mutation reduces the adhesive properties of the two proteins and prevents the formation of the tip link. In a second mutation of PCDH15, the tip link was not destroyed; the scientists suggested that the deafness is not likely caused by the breakup of the tip link but by interference with its mechanical properties.

“Now that we understand what the tip link is made of and what conditions are required to assemble it,” says Kachar, “we can study what it might take to rejoin tip links as a possible method for restoring hearing in people with some forms of hearing loss that may have resulted from disruption of the tip link.” Source: NIDCD.

Original Article

Kazmierczak K, Sakaguchi H, Tokita J, et al. Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells. Nature. 2007;449:87-91.

Selective Attenuation Increases Both Gain and Feature Selectivity

On September 19, a research report by Helsinki University of Technology, Laboratory of Computational Engineering scientists appeared in the online open-access journal PLoS ONE (Public Library of Science), showing that selective attention increases both gain and feature selectivity of the human auditory cortex.

The ability to select task-relevant sounds for awareness, while ignoring irrelevant ones, constitutes one of the most fundamental of human faculties, but the underlying neural mechanisms have remained elusive. While most of the literature explains the neural basis of selective attention by means of an increase in neural gain, a number of papers propose enhancement in neural selectivity as an alternative or a complementary mechanism.

The results of Kauramäki and colleagues, obtained by measuring electroencephalographic event-related potentials, suggest that auditory selective attention in humans cannot be explained by a gain model, where only the neural activity level is increased, but rather that selective attention additionally enhances auditory cortex frequency selectivity. Source: American Association for the Advancement of Science

Original Article

Kauramäki J, Jääskeläinen IP, Sams M. Selective attention increases both gain and feature selectivity of the human auditory cortex. Available at: www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pone.0000909.