May/June 2016
9
FEATURE
Beth Buffalo plays the video game designed for her lab's monkeys.
Photo credit: Beth Buffalo
“To successfully remember the banana’s location, he must pay close
attention to where he is in his environment,” says Beth Buffalo,
Associate Professor in the UW’s Department of Physiology and
Biophysics, who designed these video games and has worked with
monkeys since high school. “He needs to get a sense of where
the banana is relative to his position and use the landmarks to
help guide him.” By doing so, Giuseppe will successfully encode
a memory, which he can use later to retrace his steps to the invis-
ible fruit’s location.
The monkey’s ability to complete such a memory task may hinge
on a particular type of neuron, a “grid cell,” found in the medial
temporal lobe. Grid cells may help our brains create represen-
tations of newly encountered environments, which are known as
“cognitive maps.” Buffalo thinks these maps help us remember
the dimensions of a physical space, as well as aspects of time
and sensation: how long it takes to get around, and sights and
sounds we find there, for example. This comprehensive record
of new experiences helps us plan future trips.
The medial temporal lobe in humans happens to be the first spot
where the tangles of Alzheimer’s disease pathology build up and
eventually kill neurons. The disease rips apart a lifetime of cogni-
tive maps, which explains why a person’s first clinical symptoms
often begin with having trouble finding his or her way home from
the grocery store, or even around the house.
Alzheimer’s disease, a neurodegenerative condition that impairs
memory and cognitive ability and leads to dementia, affects 5.4
million Americans. This number includes 100,000 people younger
than age 65. It is the only chronic disease currently without an
effective treatment, and the number of cases is predicted to expand
to 16 million by 2050 as baby boomers age, overburdening the
national health care system and family finances.
“In order to understand what might be missing or impaired in
human patients with Alzheimer’s disease, we need to understand
how memory system works at a deep level,” says Buffalo. “We
hope to model the processes of healthy cognition, reflected in
eye movements and brain function, which can then be differen-
tiated from impaired cognition.”
To this end, the Buffalo team has found several biological markers
of memory formation in the brain—distinct patterns of neuron
firing and eye movements that predict a monkey’s success or failure
in a memory task. Aligned with the focus of the UW Alzheimer’s
Disease Research Center (ADRC), Buffalo’s goal is to translate
these cognitive biomarkers into ways to identify signs of memory
loss in people, even when there are no noticeable symptoms—a
development that could lead to earlier diagnosis and a window
for intervention. And she is close to reaching that goal.
All eyes on the prize
When she ran her lab at Emory University, Buffalo and her
colleagues learned that the primate hippocampus in the medial
temporal lobe plays a key role in guiding the eyes around a scene
based on memories of a prior viewing. Because Alzheimer’s
disease in humans targets the hippocampus, Buffalo reasoned
that signs of developing disease first appear in eye movements.
Specifically, people with mild cognitive impairment would look
around an image differently than normal controls, just like monkeys
with damage to the hippocampi.
Buffalo and her colleagues designed a computer task meant to
assess memory impairment. In a five-year NIH-sponsored study,
published in 2013, this task predicted whether participants with mild
cognitive impairment would worsen within four years. Surprisingly,
poor performance on the first round of this test predicted cogni-
tive decline, even in individuals in the healthy cohort.
“That result got us interested in the possibility that this noninvasive
behavioral diagnostic tool detects hippocampal abnormalities
associated with Alzheimer’s disease and can predict cognitive
The Buffalo Lab inserts hair-thin electrodes deep into the monkey brain to monitor
neurons during memory formation.
Photo credit: Beth Buffalo
