Researchers at Johns Hopkins have pinpointed a circuit
in the brain responsible for encoding decision-making
behavior, a circuit that, if damaged, appears to prevent a
person from altering that behavior when circumstances
change.
The discovery promises to enhance understanding of why
some brain-damaged people have learning issues, an insight
that could eventually lead to the development of more
effective treatments for those with brain injury and
trauma.
"There's a gap between current neurological treatment,
which is typically focused on treating symptoms, and
neuroscientific research, which is elucidating how the
brain works," said Michael Saddoris, a graduate student in
the Department of
Psychological and Brain Sciences in the Krieger School
of Arts and Sciences and a co-author of a paper on the
topic that appeared in a recent issue of the journal
Neuron. "Our work attempts to bridge that gap by
providing a mechanism for how the brain operates both under
damaged and normal conditions, which could provide a
framework for future treatments."
The circuit in question is located in a region of the
brain called the orbital frontal cortex, or OFC, located
right behind the eyes. It encodes the visual and other cues
that people and animals use when making decisions about
behavior or during the learning process, said co-author
Michela Gallagher, a professor of psychological and brain
sciences.
"People with lesions in this part of the brain —
from strokes or other injury — seem to learn in a
normal way but are then unable to adapt their behavior when
new situations arise, which is perplexing to us," Saddoris
said. "Though we still don't know precisely what it is
about damage to that area of the brain that causes this, we
now know where it is happening, which is an important first
step."
The researchers used laboratory rats to delve into how
the OFC might encode information about decision making, as
well as to examine how other parts of the brain are
affected when the OFC is damaged.
Electrodes were planted into the region of the rats'
brains that are involved with decision making and
communicate with the OFC. Half the rats' OFC regions were
damaged on one side of their brains. The rats — both
those with damaged and undamaged OFC regions — then
were given a task. They had to learn which odor led to a
sugar reward and which led to a bitter and unpleasant
outcome: a salty treat.
"The task we gave the rats was similar to what a human
being would experience if he was buying a soda at a machine
in a foreign country," Saddoris said. "Pushing one button
resulted in a strange-tasting salty soda, while another
resulted in a pleasant, sugary soda. After a few trials and
errors, the person would likely learn to push the button
that got him the sugary soda."
Through the electrodes, the research team was looking
for whether neurons fired more often in the presence of one
odor cue or another, the firing being a signal that the
rodent was thinking about one outcome or another, Saddoris
said.
"In the animals with lesions on their OFCs, the firing
activity developed much more slowly than it did in the
normal animals, suggesting that the OFC is critical in
helping animals learn to form associations quickly," he
said.
The researchers then challenged the rats' ability to
adapt and learn by reversing the cues so that the odor that
formerly had led to a sweet treat now resulted in a bitter
tidbit and vice versa. Continuing the soda machine analogy,
Saddoris said, "The person comes back and the button he
always pushed to get his favorite soda caused a bitter,
salty soda to come out; he'd then have to change his
strategy and figure out, all over again, how to get the
soda he wanted."
The researchers wanted to observe whether the rats
with and without damage to their OFC region were able to
track to the new outcome — a Pine Sol scent now led
to a desired sweet treat, for instance — and whether
the neuron firing was similarly affected, signaling its
impact on the decision-making process.
They found that the neural responses of the
OFC-damaged rats remained "locked in"; that is, the damaged
rats' brains were unable to adjust to the switch in
clues.
"It was as if everything was very slowed down for the
damaged rats, as if the neural system for their decision
making was moving at a fraction of its normal pace,"
Saddoris said. "It seems that OFC-lesioned animals are at
the mercy of old irrelevant information with which to make
decisions. This is likely the reason people with damage to
that area of their brains persist in behaving in certain
ways, even when it is obvious that it is not in their best
interest to do so."
According to Saddoris, these findings demonstrate that
the brain is fundamentally altered by damage to the OFC.
"It helps explain why people with damage to the OFC
behave the way they do," he said. "They have the ability to
learn normally about their world, but they have an area of
their brains that is sluggish and inflexible in guiding
their behavior, trapping them in a prison of habit, so to
speak. These findings give us insight into how the brain is
organized."
The study was supported through grants from the
National Institutes on Aging, on Drug Abuse and of Mental
Health. Materials also were provided by Stephen Warrenburg
at International Flavors and Fragrances.