How sound and vibration converge in the brain to enhance sensory experience

Ludwig van Beethoven began to lose his hearing at age 28 and was deaf by age 44. While the cause of his hearing loss remains a topic of scientific debate and ongoing revision, one thing is clear: Despite his hearing loss, Beethoven never ceased to compose music, likely because he was able to sense the vibrations of musical instruments and “hear” music through the sense of touch, researchers believe.

Now a study by Harvard Medical School researchers could help explain what enabled Beethoven, and other musicians, to develop an exquisitely refined sense of touch after losing their hearing.

The findings, based on experiments in mice and reported Dec. 18 in Cell, offer a tantalizing new clue into how and why the diminishment of one sense augments the other. They also add a surprising new twist in our understanding of how the brain and the body work in synchrony to process multiple sensations at the same time.

The research pinpoints an area in the brain called the inferior colliculus — so far studied mostly for its role in sound processing — to be also involved in processing touch signals, including mechanical vibrations detected by nerve endings on the skin.

The team’s experiments reveal that high-frequency mechanical vibrations picked up by ultra-sensitive mechanoreceptors in the skin called Pacinian corpuscles are not exclusively channeled into the somatosensory cortex — the area of the brain where bodily sensations are processed. Instead, the study found, these signals are mainly routed from the body to the inferior colliculus in the midbrain.

“This is a very surprising finding that counters the canonical view of where and how tactile sensation is processed in the brain,” said study senior author David Ginty, chair of the Department of Neurobiology at HMS and the Edward R. and Anne G. Lefler Professor of Neurobiology. “We find that a region in the midbrain’s inferior colliculus processes vibrations whether it’s vibrations in the form of sound waves acting on the inner ear or mechanical vibrations acting on the skin. When auditory and mechanical vibration signals converge in this brain region, they amplify the sensory experience, making it more salient.”
 

The ability to detect vibrations enables organisms across the animal kingdom to perceive and respond to subtle changes in their environment such as sensing and avoiding threats, which is critical for survival. For example, snakes detect the movement of both prey and predators by pressing their jaws to the ground to pick up subtle vibrations. The ability to sense vibrations is also central for the development and refinement of more complex adaptations, such as the neural rewiring of the brain that occurs after the loss of one sensation to enhance another — for example, the increasingly acute sense of hearing that develops after vision loss.

Researchers say the new findings are particularly relevant in this latter context — the neural rewiring that occurs after the loss of one sense. These insights may inform the development of prosthetics that augment tactile sensitivity in individuals with hearing loss.

“Devices that transduce sounds into tactile vibrations within the Pacinian frequency range could provide individuals with greater capacity to perceive and experience sound,” said Ginty, who is also a Howard Hughes Medical Institute investigator. “Such devices could be placed around the body and in close proximity to Pacinian neurons to enable sound-evoked mechanical vibrations of different frequencies across the hands, arms, feet, legs, and body.”

Exquisitely sensitive detectors of vibrations

The findings highlight the role of Pacinian neurons as a vital component of the somatosensory system. Their unique and elaborate structure is key to their extraordinary sensitivity. It allows them to detect even the slightest of mechanical vibrations. Each Pacinian corpuscle consists of a single nerve ending at its center, surrounded by layers of supporting cells called lamellar cells. The onion-like layers of the lamellar cell membranes act like shock absorbers, allowing the Pacinian corpuscle to respond precisely and rapidly to high-frequency vibrations while dampening low-frequency disturbances.

“Evolution has placed these receptors in different locations across the animal kingdom to suit different environments,” said study lead author Erica Huey, research fellow in the Ginty Lab. “In humans, these receptors are located deep within the skin of the fingertips and feet, while elephants, for example, have a high concentration in their feet and trunks.”

Indeed, research has shown that elephants are able to detect minute seismic vibrations through the pads of their feet and the skin of their trunk. However, until recently, scientists haven’t been able to record the activity of Pacinian neurons in an awake, freely moving animal, making it challenging to get the full picture of how sensitive these neurons truly are and what stimuli trigger their activation.

Prior research led by Josef Turecek, a postdoctoral researcher in the Ginty Lab, showed that Pacinian neurons are so sensitive that they can detect mechanical vibrations as subtle as those produced by the movement of a finger across a surface, even from meters away.

The new study builds on the previous work to explore how signals from Pacinian corpuscles are transmitted and processed in the brain. The researchers delivered mechanical vibrations at varying frequencies to the limbs of mice or to the platform that they were standing on using a mechanical stimulator, while simultaneously recording the activity of neurons in brain regions involved in sensory processing.

When they compared the responses of neurons located in two distinct brain regions, the researchers found that neurons in the ventral posterolateral nucleus of the thalamus (VPL) — a relay station for sensory information before it reaches the somatosensory cortex — were more sensitive to low-frequency vibrations. In contrast, neurons in the lateral cortex of the inferior colliculus responded preferentially to high-frequency vibrations.

To explore the role of two types of mechanoreceptors in the skin — Pacinian corpuscles and Meissner corpuscles — to the differing responses of the two brain regions to high- and low-frequency vibrations, the team studied genetically modified mice that lack either the Pacinian corpuscles or the Meissner corpuscles.

In mice without Pacinian corpuscles, neurons in the inferior colliculus showed a marked reduction in their response to high-frequency vibrations, suggesting that Pacinian corpuscles play a key role in conveying high-frequency vibrations to this area.

When the researchers exposed the mice to white noise instead of mechanical vibrations, they found that neurons in the inferior colliculus also responded, suggesting that this region processes both auditory and somatosensory stimuli.

“In fact, we observed that neurons in the inferior colliculus responded more strongly to combined tactile-auditory stimulation than to either one alone,” said Ginty.

This integration of sound and touch in the inferior colliculus of the midbrain, Ginty said, helps explain how we can both hear and physically feel the music at a concert, making the combined sensory experience a more profound one.

From an evolutionary perspective, this phenomenon is likely essential for survival, and learning more about it can inform treatments for conditions like autism and chronic neuropathy, where dysfunction leads to hypersensitivity to touch.

In future studies, the researchers are also excited to explore whether these findings are a clue for the brain’s capacity for adaptation, specifically researching if organisms develop enhanced sensitivity to vibration sensing as a compensatory mechanism in instances of hearing loss.

Authorship, funding, disclosures

Additional authors include Josef Turecek, Michelle M. Delisle, Ofer Mazor, Gabriel E. Romero, Malvika Dua, Zoe K. Sarafis, Alexis Hobble, Kevin T. Booth, Lisa V. Goodrich, and David P. Corey.

The work was supported by a HHMI Hannah Gray fellowship, NEI P30 Core Grant for Vision Research #EY012196, NIH grants F31 NS097344 and R35 5R35NS097344-05, the Edward R. and Anne G. Lefler Center for Neurodegenerative Disorders, and the Hock E. Tan and K. Lisa Yang Center for Autism Research.