How Your Brain Knows When Something Sounds ‘Off’

The Context: As we listen to the world around us, our brains can tell us when something doesn’t sound right – i.e. the wrong music note, or when a car door doesn’t shut all the way. How we can make these distinctions, however, is not well understood, and this process can be disrupted in disorders such as schizophrenia. 

The Study: Scientists have identified brain circuitry involved in making predictions about sounds – and this same circuitry can falter in schizophrenia to give rise to ‘phantom voices,’ finds a new study in Cellular Biology led by NYSCF – Robertson Neuroscience Investigator David Schneider, PhD, of NYU.

The Importance: These findings can help us understand how the brain learns sound-based skills such as speaking or playing music, and also helps pinpoint brain regions that could potentially be targeted to correct auditory hallucinations in neuropsychiatric disorders like schizophrenia.

“We listen to the sounds our movements produce to determine whether or not we made a mistake,” Dr. Schneider, an assistant professor in New York University’s Center for Neural Science and the senior author of the paper, said in a press release. 

“This is most obvious for a musician or when speaking, but our brains are actually doing this all the time, such as when a golfer listens for the sound of her club making contact with the ball. Our brains are always registering whether a sound matches or deviates from expectations,” he continued. “In our study, we discovered that the brain is able to make precise predictions about when a sound is supposed to happen and what it should sound like.”

Does That Sound Right?

To investigate how the brain makes these predictions, the team monitored brain activity in mice as they pushed a certain lever that made a tone when it reached a certain point (think: the mouse equivalent of shutting a car door).

Once mice learned that pushing the lever would be followed by the tone, the researchers then removed the sound, played the wrong sound, or played the correct sound at the wrong time. In response, mice changed their behaviors, just the way a human would if we noticed a car door didn’t shut correctly.

A peek inside the auditory cortex of these mice revealed that brain cells were only minimally active when a mouse pushed a lever and heard the expected sound. However, if the researchers played the wrong sound, or played the correct sound at the wrong time, these cells drastically increased their activity.

“The auditory cortex seems to signal not what was heard, but whether what was heard matched or violated its expectations,” noted Nicholas Audette, PhD, the first author on the study and a postdoctoral fellow in the Schneider lab. 

Not playing a sound altogether caused a select group of brain cells to activate when the sound should have occurred.

“Because these were some of the same neurons that would have been active if the sound had actually been played, it was as if the brain was recalling a memory of the sound that it thought it was going to hear,” said Dr. Schneider.

Implications for Treatments

The team noted that the same circuitry that predicted which sounds would occur can become disrupted in schizophrenia to create ‘phantom voices’: auditory hallucinations where patients hear voices that don’t exist.

The team hopes that by understanding these circuits in the healthy brain, they can begin to understand what might go wrong during disease and open the door for new treatment strategies.

Cover image credit: Schneider lab

Journal Article:

Precise movement-based predictions in the mouse auditory cortex
Nicholas J. Audette, WenXi Zhou, Alessandro La Chioma, David M. Schneider. Current Biology. 2022. DOI: https://doi.org/10.1016/j.cub.2022.09.064