An unexpected doorway into the ear opens new possibilities for hearing restoration

An international team of researchers has developed a new method to deliver drugs into the inner ear. The discovery was possible by harnessing the natural flow of fluids in the brain and employing a little understood backdoor into the cochlea. When combined to deliver a gene therapy that repairs inner ear hair cells, the researchers were able to restore hearing in deaf mice.

"These findings demonstrate that cerebrospinal fluid transport comprises an accessible route for gene delivery to the adult inner ear and may represent an important step towards using gene therapy to restore hearing in humans," said Maiken Nedergaard, MD, DMSc, senior author of the new study, which appears in the journal Science Translational Medicine.

Nedergaard is co-director of the Center for Translational Neuromedicine at University of Rochester and the University of Copenhagen. The study was the product of a collaboration between researchers at the two universities and a group led by Barbara Canlon, Ph.D. in the Laboratory of Experimental Audiology at the Karolinska Institute in Stockholm, Sweden.

The number of people worldwide predicted to have mild to complete hearing loss is expected to grow to around 2.5 billion by mid-century. The primarily cause is the death or loss of function of hair cells found in the cochlea -- which are responsible for relaying sounds to the brain -- due to mutations of critical genes, aging, noise exposure, and other factors.

While hair cells do not naturally regenerated in humans and other mammals, gene therapies have shown promise and in separate studies have successfully repaired the function of hair cells in neo-natal and very young mice. However, as both mice and humans age, the cochlea, already a delicate structure, becomes enclosed in temporal bone. At this point, any effort to reach the cochlea and deliver a gene therapy via surgery risks damaging this sensitive area and altering hearing.

In the new study, the researchers describe a little understood passage into the cochlea called the cochlear aqueduct. While the name conjures images of monumental stone architecture, the cochlear aqueduct is thin boney channel no larger than a single strand of hair. Suspected to play a role in balancing pressure in the ear, new study shows that that the cochlear aqueduct also acts as a conduit between the cerebrospinal fluid found in the inner ear and the rest of the brain.

Scientists are developing clearer picture of the mechanics of glymphatic system, the brain's unique process of removing waste first described by the Nedergaard lab in 2012. Because the glymphatic system pumps cerebrospinal fluid deep into brain tissue to wash away toxic proteins, researchers have been eyeing it as a potentially new way to deliver drugs into the brain, a major challenge in developing drugs for neurological disorders.

Researchers have also discovered that the complex movement of fluids driven by the glymphatic system extend to the eyes and the peripheral nervous system, including ear. The new study represented an opportunity to put the drug delivery potential of the glymphatic system to the test, while at the same time targeting a previously unreachable part of the auditory system.

Employing a number of imagining and modeling technologies, the researchers were able to develop a detailed portrait of how fluid from other parts of the brain flows through cochlear aqueduct and into the inner ear. The team then injected an adeno-associated virus into the cisterna magna, a large reservoir of cerebrospinal fluid found at the base of the skull. The virus found its way into the inner ear via the cochlear aqueduct, delivered a gene therapy that expresses a protein called vesicular glutamate transporter-3, which enable the hair cells to transmit signal and rescued hearing in adult deaf mice.

"This new delivery route into the ear may not only serve the advancement of auditory research, but also prove useful when translated to humans with progressive genetic-mediated hearing loss," said Nedergaard.

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Can hearing loss be reversed? Research reveals clues that could regrow the cells that help us hear

Taking a bite of an apple is considered a healthy choice. But have you ever thought about putting in earplugs before your favorite band takes the stage?

Just like your future body will thank you for the apple, your future ears (specifically your cochlear hair cells) will thank you for protecting them. The most common cause of hearing loss is progressive because these hair cells -- the primary cells to detect sound waves -- cannot regenerate if damaged or lost. People who have repeated exposure to loud noises, like military personnel, construction workers, and musicians, are most at risk for this type of hearing loss. But, it can happen to anyone over time (even concert goers).

On the other hand, birds and fish can regenerate these hair cells, and now researchers at the Del Monte Institute for Neuroscience are getting closer to identifying the mechanisms that may promote this type of regeneration in mammals, as explained in research recently published in Frontiers in Cellular Neuroscience.

"We know from our previous work that expression of an active growth gene, called ERBB2, was able to activate the growth of new hair cells (in mammals), but we didn't fully understand why," said Patricia White, PhD, professor of Neuroscience and Otolaryngology at the University of Rochester Medical Center. The 2018 study led by Jingyuan Zhang, PhD, a postdoctoral fellow in the White lab at the time, found that activating the growth gene ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to multiply and activate other neighboring stem cells to become new sensory hair cells.

"This new study tells us how that activation is happening -- a significant advance toward the ultimate goal of generating new cochlear hair cells in mammals," said White.

Using single-cell RNA sequencing in mice, researchers compared cells with an overactive growth gene (ERBB2 signaling) with similar cells that lacked such signaling. They found the growth gene -- ERBB2 -- promoted stem cell-like development by initiating the expression of multiple proteins -- including SPP1, a protein that signals through the CD44 receptor. The CD44 receptor is known to be present in cochlear-supporting cells. This increase in cellular response promoted mitosis in the supporting cells, a key event for regeneration.

"When we checked this process in adult mice, we were able to show that ERBB2 expression drove the protein expression of SPP1 that is necessary to activate CD44 and grow new hair cells," said Dorota Piekna-Przybylska, PhD, a staff scientist in the White Lab and first author of the study. "This discovery has made it clear that regeneration is not only restricted to the early stages of development. We believe we can use these findings to drive regeneration in adults."

"We plan to further investigation of this phenomenon from a mechanistic perspective to determine whether it can improve auditory function after damage in mammals. That is the ultimate goal," said White.

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New tool to create hearing cells lost in aging

Hearing loss due to aging, noise and certain cancer therapy drugs and antibiotics has been irreversible because scientists have not been able to reprogram existing cells to develop into the outer and inner ear sensory cells -- essential for hearing -- once they die.

But Northwestern Medicine scientists have discovered a single master gene that programs ear hair cells into either outer or inner ones, overcoming a major hurdle that had prevented the development of these cells to restore hearing.

The study will be published in Nature May 4.

"Our finding gives us the us the first clear cell switch to make one type versus the other," said lead study author Jaime Garcia-Anoveros, professor of anesthesia, neurology and neuroscience at Northwestern University Feinberg School of Medicine. "It will provide a previously unavailable tool to make an inner or outer hair cell. We have overcome a major hurdle."

About 8.5 percent of adults aged 55 to 64 in the U.S. have disabling hearing loss. That increases to nearly 25 percent of those aged 65 to 74 and 50 percent of those who are 75 and older, reports the Centers for Disease Control.

Currently, scientists can produce an artificial hair cell, but it does not differentiate into an inner or outer cell, which provide different essential functions to produce hearing. The discovery is a major step towards developing these specific cells.

"It's like a ballet" as cells crouch and leap

The death of outer hair cells made by the cochlea are most often the cause of deafness and hearing loss. The cells develop in the embryo and do not reproduce. The outer hair cells expand and contract in response to the pressure of sound waves and amplify sound for the inner hair cells. The inner cells transmit those vibrations to the neurons to create the sounds we hear.

"It's like a ballet," Garcia-Anoveros says with awe as he describes the coordinated movement of the inner and outer cells. "The outers crouch and jump and lift the inners further into the ear.

"The ear is a beautiful organ. There is no other organ in a mammal where the cells are so precisely positioned. (I mean, with micrometric precision). Otherwise, hearing doesn't occur."

The master gene switch Northwestern scientists discovered that programs the ear hair cells is TBX2. When the gene is expressed, the cell becomes an inner hair cell. When the gene is blocked, the cell becomes an outer hair cell. The ability to produce one of these cells will require a gene cocktail, Garcia-Anoveros said. The ATOH1 and GF1 genes are needed to make a cochlear hair cell from a non-hair cell. Then the TBX2 would be turned on or off to produce the needed inner or outer cell.

The goal would be to reprogram supporting cells, which are latticed among the hair cells and provide them with structural support, into outer or inner hair cells.

"We can now figure out how to make specifically inner or outer hair cells and identify why the later are more prone to dying and cause deafness," Garcia-Anoveros said. He stressed this research is still in the experimental stage.

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What do you see when you listen to music?

Are we all imagining the same thing when we listen to music, or are our experiences hopelessly subjective? In other words, is music a truly universal language?

To investigate those questions, an international team of researchers (including a classical pianist, a rock drummer and a concert bassist) asked hundreds of people what stories they imagined when listening to instrumental music. The results appeared recently in the Proceedings of the National Academy of Sciences.

The researchers, led by Princeton's Elizabeth Margulis and Devin McAuley of Michigan State University, discovered that listeners in Michigan and Arkansas imagined very similar scenes, while listeners in China envisioned completely different stories.

"These results paint a more complex picture of music's power," said Margulis, a professor of music who uses theoretical, behavioral and neuroimaging methodologies to investigate the dynamic experience of listeners. "Music can generate remarkably similar stories in listeners' minds, but the degree to which these imagined narratives are shared depends on the degree to which culture is shared across listeners."

The 622 participants came from three regions across two continents: two suburban college towns in middle America -- one in Arkansas and the other in Michigan -- and a group from Dimen, a village in rural China where the primary language is Dong, a tonal language not related to Mandarin, and where the residents have little access to Western media.

All three groups of listeners -- in Arkansas, Michigan and Dimen -- heard the same 32 musical stimuli: 60-second snippets of instrumental music, half from Western music and half from Chinese music, all without lyrics. After each musical excerpt, they provided free-response descriptions of the stories they envisioned while they listened.

The results were striking. Listeners in Arkansas and Michigan described very similar stories, often using the same words, while the Dimen listeners envisioned stories that were similar to each other but very different from those of American listeners.

For example, a musical passage identified only as W9 brought to mind a sunrise over a forest, with animals waking and birds chirping for American listeners, while those in Dimen pictured a man blowing a leaf on a mountain, singing a song to his beloved. For musical passage C16, Arkansas and Michigan listeners described a cowboy, sitting alone in the desert sun, looking out over an empty town; participants in Dimen imagined a man in ancient times sorrowfully contemplating the loss of his beloved.

Quantifying similarities between free-response stories required huge amounts of natural language data processing. The tools and strategies that they developed will be useful in future studies, said Margulis, who is also the director of Princeton's Music Cognition lab. "Being able to map out these semantic overlaps, using tools from natural language processing, is exciting and very promising for future studies that, like this one, straddle the border between the humanities and the sciences."

"It's amazing," said co-author Benjamin Kubit, a drummer and a postdoctoral research associate previously in the Princeton Neuroscience Institute and now in the Department of Music. "You can take two random people who grew up in a similar environment, have them listen to a song they haven't heard before, ask them to imagine a narrative, and you'll find similarities. However, if those two people don't share a culture or geographical location, you won't see that same kind of similarity in experience. So while we imagine music can bring people together, the opposite can also be true -- it can distinguish between sets of people with a different background or culture."

Though the researchers had carefully ensured that the pieces they chose had never appeared in a movie soundtrack or any other setting that would prescribe visuals, the same music sparked very similar visuals in hundreds of listeners -- unless they had grown up in a different cultural context.

"It's stunning to me that some of these visceral, hard-to-articulate, imagined responses we have to music can actually be widely shared," said Margulis. "There's something about that that's really puzzling and compelling, especially because the way we encounter music in 2022 is often solitary, over headphones. But it turns out, it's still a shared experience, almost like a shared dream. I find it really surprising and fascinating -- with the caveat, of course, that it's not universally shared, but depends on a common set of cultural experiences."

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Spiders use webs to extend their hearing

Everyone knows that humans and most other vertebrate species hear using eardrums that turn soundwave pressure into signals for our brains. But what about smaller animals like insects and arthropods? Can they detect sounds? And if so, how?

Distinguished Professor Ron Miles, a Department of Mechanical Engineering faculty member at Binghamton University's Thomas J. Watson College of Engineering and Applied Science, has been exploring that question for more than three decades, in a quest to revolutionize microphone technology.

A newly published study of orb-weaving spiders -- the species featured in the classic children's book "Charlotte's Web" -- has yielded some extraordinary results: The spiders are using their webs as extended auditory arrays to capture sounds, possibly giving spiders advanced warning of incoming prey or predators.

The paper, "Outsourced Hearing in an Orb-Weaving Spider that Uses its Web as an Auditory Sensor," published March 29 in the Proceedings of the National Academy of Sciences, provides the first evidence that a spider can outsource hearing to its web.

It is well-known that spiders respond when something vibrates their webs, such as potential prey. In these new experiments, researchers for the first time show that spiders turned, crouched or flattened out in response to sounds in the air.

The study is the latest collaboration between Miles and Ron Hoy, a biology professor from Cornell, and it has implications for designing extremely sensitive bio-inspired microphones for use in hearing aids and cell phones.

Jian Zhou, who earned his PhD in Miles' lab and is doing postdoctoral research at the Argonne National Laboratory, and Junpeng Lai, a current PhD student in Miles' lab, are co-first authors. Miles, Hoy and Associate Professor Carol I. Miles from the Harpur College of Arts and Sciences' Department of Biological Sciences at Binghamton are also authors for this study. Grants from the National Institutes of Health to Ron Miles funded the research.

A single strand of spider silk is so thin and sensitive that it can detect the movement of vibrating air particles that make up a soundwave, which is different from how eardrums work. Ron Miles' previous research has led to the invention of novel microphone designs that are based on hearing in insects.

"The spider is really a natural demonstration that this is a viable way to sense sound using viscous forces in the air on thin fibers," he said. "If it works in nature, maybe we should have a closer look at it."

Spiders can detect miniscule movements and vibrations through sensory organs on their tarsal claws at the tips of their legs, which they use to grasp their webs. Orb-weaver spiders are known to make large webs, creating a kind of acoustic antennae with a sound-sensitive surface area that is up to 10,000 times greater than the spider itself.

In the study, the researchers used Binghamton University's anechoic chamber, a completely soundproof room under the Innovative Technologies Complex. Collecting orb-weavers from windows around campus, they had the spiders spin a web inside a rectangular frame so they could position it where they wanted.

The team began by using pure tone sound 3 meters away at different sound levels to see if the spiders responded or not. Surprisingly, they found spiders can respond to sound levels as low as 68 decibels. For louder sound, they found even more types of behaviors.

They then placed the sound source at a 45-degree angle, to see if the spiders behaved differently. They found that not only are the spiders localizing the sound source, but they can tell the sound incoming direction with 100% accuracy.

To better understand the spider-hearing mechanism, the researchers used laser vibrometry and measured over one thousand locations on a natural spider web, with the spider sitting in the center under the sound field. The result showed that the web moves with sound almost at maximum physical efficiency across an ultra-wide frequency range.

"Of course, the real question is, if the web is moving like that, does the spider hear using it?" Miles said. "That's a hard question to answer."

Lai added: "There could even be a hidden ear within the spider body that we don't know about."

So the team placed a mini-speaker 5 centimeters away from the center of the web where the spider sits, and 2 millimeters away from the web plane -- close but not touching the web. This allows the sound to travel to the spider both through air and through the web. The researchers found that the soundwave from the mini-speaker died out significantly as it traveled through the air, but it propagated readily through the web with little attenuation. The sound level was still at around 68 decibels when it reached the spider. The behavior data showed that four out of 12 spiders responded to this web-borne signal.

Those reactions proved that the spiders could hear through the webs, and Lai was thrilled when that happened: "I've been working on this research for five years. That's a long time, and it's great to see all these efforts will become something that everybody can read."

The researchers also found that, by crouching and stretching, spiders may be changing the tension of the silk strands, thereby tuning them to pick up different frequencies. By using this external structure to hear, the spider could be able to customize it to hear different sorts of sounds.

Future experiments may investigate how spiders make use of the sound they can detect using their web. Additionally, the team would like to test whether other types of web-weaving spiders also use their silk to outsource their hearing.

"It's reasonable to guess that a similar spider on a similar web would respond in a similar way," Ron Miles said. "But we can't draw any conclusions about that, since we tested a certain kind of spider that happens to be pretty common."

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When the brain switches from hearing to listening

What happens in the brain when simply hearing becomes listening? To answer this question, researchers at the University of Basel have traced the neuronal fingerprint of the two types of sound processing in the mouse brain.

It is intuitively clear to us that there is a difference between passive hearing and active listening. Attention and an animated state, but also movement, play a role in how sound processing in the brain adjusts accordingly. Neuroscientists Professor Tania Rinaldi Barkat and Dr. Gioia De Franceschi from the Department of Biomedicine at the University of Basel have provided an accurate account of what happens in this process in the journal Cell Reports.

For their study, the researchers examined the activity of neurons in four different areas in the brains of mice known to be involved in increasingly complex sound processing. During the experiment, the animals were either passively hearing the sounds played to them, or actively listening to them to receive a reward for detecting the sounds.

Activity pattern depends on various factors

It was shown that the majority of neurons changed their activity when switching between hearing and listening. "But this doesn't mean that all neurons behaved the same way," explains De Franceschi. "We actually found ten distinct and specific types of activity change."

While most of the neurons showed a change that was probably related to varying levels of attention, some of them also showed patterns of activity that were related to the arousal level of the mice, their movement, the availability of a reward, or a combination of these factors.

Impact on all processing levels

The auditory pathway in the brain consists of a number of different nuclei that relay acoustic information from the cochlea to the primary auditory cortex. Two of the four areas along the auditory pathway studied by the researchers are thought to be at a "higher level" in terms of processing complexity. "At the beginning of our study, we suspected that these were the areas particularly affected by attention to sounds," said Barkat. "Surprisingly, however, this wasn't the case." Attention also alters activity in brain areas previously thought to perform only basic forms of sound processing.

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A common ancestor for cells involved in hearing and touch

The sensory cells in the inner ear and the touch receptors in the skin actually have a lot in common, according to a new study from the USC Stem Cell laboratory of Neil Segil published in the Proceedings of the National Academy of Sciences (PNAS).

"There are striking similarities in the development of two types of specialized sensory cells: the so-called 'hair cells' that receive sound vibrations in the inner ear, and the Merkel cells that sense light touch at the surface of the skin," said Segil, who is a Professor in the Department of Stem Cell Biology and Regenerative Medicine, and the USC Tina and Rick Caruso Department of Otolaryngology -- Head and Neck Surgery. "Ultimately, these developmental similarities are a legacy of shared evolutionary history. This demonstrates how the story of evolutionary developmental biology, or 'evo devo,' also extends to what we call the 'epigenetic level' -- or how genes are regulated."

In the study, PhD student Haoze (Vincent) Yu, postdoctoral scholar Litao Tao, and their colleagues identified a shared mechanism involved in gene regulation or epigenetics, that enables stem cells and progenitor cells to differentiate into more specialized hair cells and Merkel cells.

In order to begin the process of differentiation, the right parts of a stem cell's DNA need to be taken out of storage. Each human cell can store around six feet of DNA in its nucleus, because this DNA is wound around tiny "spools" made up of proteins called histones. These spools of DNA and histone protein are further packed together to form what are known are nucleosomes, which are stacked to create chromatin, which is the material that makes up the chromosomes.

When DNA is wound tightly into this storage configuration, the chromatin is closed and inaccessible to the protein ATOH1. This protein is a "master regulator" that can activate a network of differentiation genes in the DNA within the chromatin -- but not without first gaining access.

To this end, ATOH1 stimulates the production of a second protein known as POU4F3, an aptly named "pioneer factor" with the ability to venture into new frontiers by binding to closed and inaccessible chromatin. After POU4F3 blazes a trail by binding to the closed chromatin, ATOH1 is able to move forward with engaging and activating the network of genes that drives differentiation into hair cells and Merkel cells.

Strikingly, there is significant overlap in the specific regions of chromatin that POU4F3 makes accessible to ATOH1 in hair cells and Merkel cells.

"It's remarkable that these two cell types, which are both involved in sensing mechanical stimuli but derive from distinct parts of the embryo, both rely on the same ATOH1/POU4F3 mechanism in order to differentiate," said Segil. "Our study suggests that this mechanism is extremely ancient, and emerged before hair cells and Merkel cells diverged from a common evolutionary ancestor -- an 'ur-mechanoreceptor' cell type."

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Closer to gene therapy that would restore hearing for the congenitally deaf

Researchers at Oregon State University have found a key new piece of the puzzle in the quest to use gene therapy to enable people born deaf to hear.

The work centers around a large gene responsible for an inner-ear protein, otoferlin. Mutations in otoferlin are linked to severe congenital hearing loss, a common type of deafness in which patients can hear almost nothing.

"For a long time otoferlin seemed to be a one-trick pony of a protein," said Colin Johnson, associate professor of biochemistry and biophysics in the OSU College of Science. "A lot of genes will find various things to do, but the otoferlin gene had appeared only to have one purpose and that was to encode sound in the sensory hair cells in the inner ear. Small mutations in otoferlin render people profoundly deaf."

In its regular form, the otoferlin gene is too big to package into a delivery vehicle for molecular therapy, so Johnson's team is looking at using a truncated version instead.

Research led by graduate student Aayushi Manchanda showed the shortened version needs to include a part of the gene known as the transmembrane domain, and one of the reasons for that was unexpected: Without the transmembrane domain, the sensory cells were slow to mature.

"That was surprising since otoferlin was known to help encode hearing information but had not been thought to be involved in sensory cell development," Johnson said.

Findings were published today in Molecular Biology of the Cell.

Scientists in Johnson's lab have been working for years with the otoferlin molecule and in 2017 they identified a truncated form of the gene that can function in the encoding of sound.

To test whether the transmembrane domain of otoferlin needed to be part of the shortened version of the gene, Manchanda introduced a mutation that truncated the transmembrane domain in zebrafish.

Zebrafish, a small freshwater species that go from a cell to a swimming fish in about five days, share a remarkable similarity to humans at the molecular, genetic and cellular levels, meaning many zebrafish findings are immediately relevant to humans. Embryonic zebrafish are transparent and can be easily maintained in small amounts of water.

"The transmembrane domain tethers otoferlin to the cell membrane and intracellular vesicles but it was not clear if this was essential and had to be included in a shortened form of otoferlin," Manchanda said. "We found that the loss of the transmembrane domain results in the sensory hair cells producing less otoferlin as well as deficits in hair cell activity. The mutation also caused a delay in the maturation of the sensory cells, which was a surprise. Overall the results argue that the transmembrane domain must be included in any gene therapy construct."

At the molecular level, Manchanda found that a lack of transmembrane domain led to otoferlin failing to properly link the synaptic vesicles filled with neurotransmitter to the cell membrane, causing less neurotransmitter to be released.

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Study shows how our brains sync hearing with vision

Every high-school physics student learns that sound and light travel at very different speeds. If the brain did not account for this difference, it would be much harder for us to tell where sounds came from, and how they are related to what we see.

Instead, the brain allows us to make better sense of our world by playing tricks, so that a visual and a sound created at the same time are perceived as synchronous, even though they reach the brain and are processed by neural circuits at different speeds.

One of the brain's tricks is temporal recalibration: altering our sense of time to synchronize our joint perception of sound and vision. A new study finds that recalibration depends on brain signals constantly adapting to our environment to sample, order and associate competing sensory inputs together.

Scientists at The Neuro (Montreal Neurological Institute-Hospital) of McGill university recruited volunteers to view short flashes of light paired with sounds with a variety of delays and asked them to report whether they thought both happened at the same time. The participants performed this task inside a magnetoencephalography (MEG) machine, which recorded and imaged their brain waves with millisecond precision. The audio-visual pairs of stimuli changed each time, with sounds and visual objects presented closer or farther apart in time, and with random orders of presentation.

The researchers found that the volunteers' perception of simultaneity between the audio and visual stimuli in a pair was strongly affected by the perceived simultaneity of the stimulus pair before it. For example, if presented with a sound followed by a visual milliseconds apart and perceived as asynchronous, one is much more likely to report the next audio-visual stimulus pair as synchronous, even when it's not. This form of active temporal recalibration is one of the tools used by the brain to avoid a distorted or disconnected perception of reality, and help establish causal relations between the images and sounds we perceive, despite different physical velocities and neural processing speeds.

The MEG signals revealed that this brain feat was enabled by a unique interaction between fast and slow brain waves in auditory and visual brain regions. Slower brain rhythms pace the temporal fluctuations of excitability in brain circuits. The higher the excitability, the easier an external input is registered and processed by receiving neural networks.

Based on this, the researchers propose a new model for understanding recalibration, whereby faster oscillations riding on top of slower fluctuations create discrete and ordered time slots to register the order of sensory inputs. For example, when an audio signal reaches the first available time slot in the auditory cortex and so does a visual input, the pair is perceived as simultaneous. For this to happen, the brain needs to position the visual time slots a bit later than the auditory ones to account for the slower physiological transduction of visual signals. The researchers found that this relative delay between neural auditory and visual time slots is a dynamic process that constantly adapts to each participant's recent exposure to audiovisual perception.

Their data confirmed the new dynamic integration model by showing how these subtle tens-of-millisecond delays of fast brain oscillations can be measured in every individual and explain their respective judgments of perceived simultaneity.

In autism and speech disorders, the processing of the senses, especially hearing, is altered. In schizophrenia as well, patients can be affected by perceived distortions of sensory inputs. The neurophysiological mechanisms of temporal recalibration described in this study may be altered in these disorders, and their discovery may reveal new research goals to improve these deficits.

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We hear what we expect to hear

 Humans depend on their senses to perceive the world, themselves and each other. Despite senses being the only window to the outside world, people do rarely question how faithfully they represent the external physical reality. During the last 20 years, neuroscience research has revealed that the cerebral cortex constantly generates predictions on what will happen next, and that neurons in charge of sensory processing only encode the difference between our predictions and the actual reality.

A team of neuroscientists of TU Dresden headed by Prof Dr Katharina von Kriegstein presents new findings that show that not only the cerebral cortex, but the entire auditory pathway, represents sounds according to prior expectations.

For their study, the team used functional magnetic resonance imaging (fMRI) to measure brain responses of 19 participants while they were listening to sequences of sounds. The participants were instructed to find which of the sounds in the sequence deviated from the others. Then, the participants' expectations were manipulated so that they would expect the deviant sound in certain positions of the sequences. The neuroscientists examined the responses elicited by the deviant sounds in the two principal nuclei of the subcortical pathway responsible for auditory processing: the inferior colliculus and the medial geniculate body. Although participants recognised the deviant faster when it was placed on positions where they expected it, the subcortical nuclei encoded the sounds only when they were placed in unexpected positions.

These results can be best interpreted in the context of predictive coding, a general theory of sensory processing that describes perception as a process of hypothesis testing. Predictive coding assumes that the brain is constantly generating predictions about how the physical world will look, sound, feel, and smell like in the next instant, and that neurons in charge of processing our senses save resources by representing only the differences between these predictions and the actual physical world.

Dr Alejandro Tabas, first author of the publication, states on the findings: "Our subjective beliefs on the physical world have a decisive role on how we perceive reality. Decades of research in neuroscience had already shown that the cerebral cortex, the part of the brain that is most developed in humans and apes, scans the sensory world by testing these beliefs against the actual sensory information. We have now shown that this process also dominates the most primitive and evolutionary conserved parts of the brain. All that we perceive might be deeply contaminated by our subjective beliefs on the physical world."

These new results open up new ways for neuroscientists studying sensory processing in humans towards the subcortical pathways. Perhaps due to the axiomatic belief that subjectivity is inherently human, and the fact that the cerebral cortex is the major point of divergence between the human and other mammal's brains, little attention has been paid before to the role that subjective beliefs could have on subcortical sensory representations.

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