Auditory research study to further tinnitus knowledge

In the quest to learn more about the brain and brain diseases, Dr. Majid Mohajerani has been assembling a team of researchers—three graduate students, three post-doctoral researchers, a research associate and two technicians—as he’s been building a state-of-the-art optical imaging lab.

Dr. Michael Kyweriga is one of the post-doctoral researchers and he’s investigating tinnitus. He’s currently conducting a study to determine if the parietal association area of the brain is involved in a task that requires a transgenic mouse to discriminate between two auditory tones.

Dr. Michael Kyweriga

“Many people are aware of the cocktail party effect, which is when you’re in a noisy environment and you’re talking to your friend but there’s all these distracting sounds. You are able to tune out those distracting sounds. That’s a form of attention called top-down control, where you try to suppress other inputs and pay attention to what your friend is saying. How the brain does this is not well understood,” he says.

Researchers like Kyweriga have some candidate regions of the brain that might be involved, one of them being the parietal association area. At a cocktail party, a person’s ears receive information about the sounds in the environment. The signals travel on the auditory nerves and on to the brain’s auditory cortex for further processing.

“When the signals get up into the cerebral cortex—the wrinkly, thinky part of the brain—that’s where we start assigning meaning to sounds, identifying songs or a person’s voice. Beyond that are these association areas that are now starting to draw in memories and accessing other parts of the brain that pull all this together,” says Kyweriga. “We’re trying to deal with the information as we try to listen to a friend speak and some people will close a door or put their dominant ear closer to the person to cut out other distractors.”

How people are able to direct their attention through top-down control, by willing themselves to pay attention, has eluded scientists for a long time. Some scientists have speculated that tinnitus could be a disorder of top-down control. If Kyweriga can show that the parietal association area is involved in top-down control, then he can test whether tinnitus is the result of faulty top-down control. Only with the tools in Mohajerani’s lab can these hypotheses be tested.

Kyweriga is training mice to learn whether a high- or low-frequency tone is associated with a reward. Once the mice have been sufficiently trained, a fibre optic connector is implanted close to the surface of their brains. To test his hypothesis, the mice do the auditory task again.

“While they’re doing the task and, simultaneously with them getting the sound, we’re going to turn on the blue light and that should either disrupt or enhance their neural responses to the sound,” says Kyweriga. “This is a really cool set of experiments that we’re able to do here with all the technology that we have and get to answering these long-standing questions we have in neuroscience about how our brains are able to do these type of things.”

As researchers like Kyweriga uncover more of the secrets of how the brain works, the higher is the likelihood of developing therapeutic approaches that will help people with tinnitus.

While Kyweriga uses lasers to alter the behaviour of his mice subjects, another post-doctoral researcher, Dr. Maurice Needham, uses lasers to view neuronal activity and provides expertise on the technical side of things. He’s in charge of making sure the optical equipment runs properly, including the two new shiny two-photon microscopes placed on a stainless steel table that’s suspended on air.

Dr. Maurice Needham
“The reason it’s suspended on air is to eliminate vibrations because when you have so many components working so finely, you have to ensure that any minor movements emanating from the building will be absorbed by this table. Any vibrations from the ground first have to move the heavy stainless steel table and even if that happens, the air cushion protects the stability of the tabletop and thus the images,” says Needham. “When it comes to two-photon imaging, this is probably the most advanced system you can buy.”

Needham has been at the U of L for five years and during that time he’s become more familiar with imaging systems. When the two-photon microscopes were installed, Needham watched, listened and learned so now he’s in charge of making sure they continue to work and performing any necessary repairs.

“Once Majid started increasing the amount of imaging systems here, we connected because I was interested,” he says.

While two-photon systems have been available for years, Mohajerani’s system is special. In addition to being very fast, it can simultaneously stimulate specific brain regions while viewing the subsequent response. It can also look much deeper into brain tissue than previous systems. This will be of great benefit to many experiments in Mohajerani’s lab, including Kyweriga’s work on tinnitus.

“All research requires the sharing of data. Seeing numbers and graphs is one thing but seeing pretty images is always the best. A picture is worth a thousand words,” says Needham. “We are one of only two labs in Canada with this imaging set-up, making us competitive on the world stage for neuroscience research. These systems, along with the new two-photon tomography system, will elevate this research centre’s technical abilities to compete with the best universities in the world.”