Summary: New research focuses on how memory can impact the perception of auditory and visual information.
Source: Harvard
Aleena
Garner still remembers the moment she decided to pursue neurobiology.
She was in an undergraduate chemistry class when realization struck: the
human brain—that three-pound organ capable of carrying out an endless
array of sophisticated tasks—is made up of the very same elements as
yogurt.
“Despite
having a similar composition as yogurt, our brains are considerably
more capable. How can this be? That’s a big question I’ve had for a long
time,” Garner said.
Garner,
who recently became an assistant professor of neurobiology in the
Blavatnik Institute at Harvard Medical School, is tackling this question
by exploring how the brain processes sensory information.
In a conversation with Harvard Medicine News, Garner delved into her research, which focuses on how memory affects perception of visual and auditory information.
Understanding
these interactions will not only advance general understanding of the
brain, she said, but could be useful in situations like post-traumatic
stress disorder (PTSD), where they become disrupted.
HMNews: Why are you studying perception in the context of memory?
Garner: Traditionally,
we think about memory as occurring in a higher-order cognitive region
of the brain that is separate from the sensory regions that process more
basic information about the world. Thus, it makes sense to look at
sensory regions with respect to visual information that enters the eye
and auditory information that enters the ear.
However,
we don’t understand why there seems to be more feedback from the
higher-order cognitive areas to the sensory regions than from receptor
organs like the eye and the ear.
We
also don’t know why the auditory cortex and visual cortex communicate
with each other before sending information to higher-order brain
regions. It makes sense that we would want to form a pure image of what
we’re seeing or hearing in the world, but the anatomy of the brain
suggests that we’re actually altering what we perceive in our early
sensory regions before this information gets to higher-order cognitive
areas.
One
of the big goals in my lab is to investigate the communication between
the early sensory regions and the higher-order cognitive regions of the
brain to understand how they’re interacting.
More
specifically, we want to know how do we use memory. One application of
memory could be to build a picture of the world so that we can predict
what’s going to happen.
If
you walk into a new room, you understand that you can’t walk through
the walls because you can make predictions in a new context based on
what you already know. You know you can pick up a glass of water and
drink from it, so you don’t need to spend very much neural power
processing that information. Instead, your brain spends more energy
processing a conversation with another person and thinking about things
you didn’t expect, such as a question you’ve never been asked before.
Your brain can then update its model to incorporate this new
information.
Memories
let us spend less energy processing the things that we expect, enabling
us to amplify the signal of the things we don’t expect. We are
interested in how this process works.
HMNews: Do you have other examples of how memory can alter our interpretation of sensory information?
Garner: If
you are on the sidewalk and you hear a siren as you’re about to step
into a crosswalk, you’d stop because experience tells you that an
ambulance is driving by. In that moment, your auditory sense triggers
the visual image of an ambulance.
However,
maybe the siren ends up being a child’s toy instead of an ambulance. If
that happens often enough, eventually, when you hear the siren, you
will think it’s just somebody’s toy, and you’ll walk into the crosswalk
anyway. This is because your experience and memory have actually changed
your picture of the world, and thus you interpret the siren
differently.
Sometimes,
the same stimulus is integrated into two different memories, one
positive and one negative. Then the question becomes how does your brain
know how to react. That will depend on the other sensory cues around
the stimulus.
If
you see a picture and hear a bell, that may mean you are going to
receive a reward, but if you see the same picture and hear a knocking
sound, that may mean you are going to receive a punishment. In this
example, your experience with the auditory information changes how you
interpret the visual information.
We want to know how the brain makes these adjustments and where these changes are happening.
HMNews: Are there potential applications of your research that interest you?
Garner: A
longer-term goal of the lab is to look at cases related to trauma such
as PTSD. Normally, people can distinguish when a stimulus is safe and
when it’s not safe. However, in PTSD, this ability becomes disrupted,
and one of the symptoms can be to overgeneralize and be fearful of a
stimulus even when you don’t need to be. This fear response can cause a
physical reaction such as tensing muscles and freezing.
There’s
some work in humans looking at how the brainstem is involved in body
physiology and how we react to stimuli. I want to look at connections
between the brainstem and cortical regions of the brain to see how the
communication works and how it becomes disrupted after trauma—first in
mice, and eventually in humans.
I’m
also interested in motor-related functions of the brain. I was in
physical therapy for a while after a rock-climbing accident, and I met
patients with Parkinson’s disease who were training in rehabilitation
and physical therapy to get better. It’s remarkable—physical therapy and
training does help with the symptoms even though Parkinson’s is a
neurodegenerative disease.
I
want to explore interventions for neurodegenerative diseases that are
based on the connectivity between the sensory regions of the cortex and
the brainstem. Such interventions may be able to train the brain to have
more motor function even as some of the primary motor areas
deteriorate.
HMNews: You recently published a paper in Nature Neuroscience that explored memory and audiovisual predictions in mice. What did you find out?
Garner: The
motivation for the work was a basic question: If a visual stimulus is
integrated into a memory, is it represented differently in the primary
visual cortex of the brain? In other words, is a visual stimulus that is
presented in a relatively neutral way processed differently by the
brain than the same stimulus presented during a specific memory
retrieval. In the study, we used an auditory cue to trigger a memory
about a visual stimulus.
It
turned out that there was a difference. The response to the visual
stimulus was suppressed after the mouse learned to associate it with a
memory-triggering auditory cue. But we didn’t know what was causing this
suppression. Scientists have established that there is a large
projection from the auditory cortex to the visual cortex in both
primates and mice, but the function of this pathway is not understood,
so we decided to investigate it.
We
found that the auditory axons had auditory and visual responses, and
the number of visually responsive axons increased as the mouse was
trained to associate the auditory and visual cues.
We
then developed a functional mapping technique that involved
synthetically exciting auditory input to the visual cortex while looking
at the effects on activity of visual cortex neurons. Intriguingly, when
we excited auditory input, we saw selective suppression of visual
cortex neurons that were responsive to the visual stimulus associated
with the auditory cue—but only after the mouse learned to associate the
visual stimulus with the auditory cue.
Indeed,
these visual cortex neurons that were inhibited by synthetic
stimulation of auditory input were mostly responsible for the
suppression of the visual response after the mouse learned the auditory
cue.
These
results give us a mechanism to explain the experience-dependent
suppression of visual responses following a learned, predictive,
auditory cue.
HMNews: In your research you use a virtual reality system designed for mice. How does it work?
Garner: In
the system, a mouse is on a spherical treadmill—a ball on air with a
dome-shaped screen around it. The treadmill allows the mouse to rotate
its torso and move its legs in different directions, but keeps the mouse
in place so we can measure the activity of hundreds of neurons in its
brain. Then, we yoke the movement of the mouse to whatever we project
onto the walls of the dome, creating a virtual reality where, as the
mouse turns, the world does a counter turn, just like in real life.
This
setup allows us to have precise temporal and spatial control over the
auditory and visual stimuli that a mouse is experiencing. We create
virtual walls in the dome, so the mouse can locomote to the wall, but
can’t pass through. We also project different types of visual patterns
and shapes on the walls and present sounds using a surround sound
system. It’s kind of like an interactive, 3-D IMAX theater sized for a
mouse.
We then use calcium imaging to record neural activity as the mouse explores this interactive, virtual world.
HMNews: Your description makes me think of a mouse playing a video game…
Garner: Yes,
that’s exactly what it is [laughs]. With virtual reality we can do all
kinds of interesting things without having to physically pick up the
mouse and move it from one location to another, which affects behavior,
and even transcription of genes.
We
can flip a switch to instantly change the environment, so we can look
at contextual learning without changing anything but the context. That
would be impossible in a real environment.
Christopher
Harvey, an associate professor of neurobiology at HMS, developed this
technology during his postdoctoral work, so I’m very excited to be
working in the same department as him. It’s an outstanding opportunity.
HMNews: Beyond your research, what do you hope to be involved in at HMS?
Garner: I
love teaching—it’s one of the reasons I went into academic science.
Even if you don’t realize that you’re good at something, a teacher can
bring that out, which can alter the course of your life. That’s one of
the reasons I was attracted to Harvard. There seems to be genuine
support for teaching, and a positive attitude about the importance of
teaching.
I’m
also part of a group called the Leading Edge Symposium that was founded
by Kara McKinley, an assistant professor of stem cell and regenerative
biology at Harvard. The group aims to support women and nonbinary
individuals in the sciences.
Postdocs
from anywhere can apply, and the program provides support during job
applications: participants can give practice talks, get feedback on
application materials—lots of things that not everybody gets at their
institution. It’s wonderfully supportive, and I don’t think I would have
done so well interviewing without being in the group as a postdoc.
There are different levels of approaching the issue of gender equity in
science, and I think the small-scale level of teaching and mentoring
individual people is very important.
Of
course, I want to have a large influence, but if I affect two people,
and those two people are successful and start their own labs, then they
can each influence two more people. You start to get this exponential
growth.
About this memory research news
Author: Catherine Caruso
Source: Harvard
Contact: Catherine Caruso – Harvard
Image: The image is in the public domain
Original Research: Closed access.
“A cortical circuit for audio-visual predictions” by Aleena R. Garner et al. Nature Neuroscience