As people age, they often lose their motivation to learn new things or engage in everyday activities. In a study of mice, MIT neuroscientists have now identified a brain circuit that is critical for maintaining this kind of motivation.
This circuit is particularly important for learning to
make decisions that require evaluating the cost and reward that come with a
particular action. The researchers showed that they could boost older mice’s
motivation to engage in this type of learning by reactivating this circuit, and
they could also decrease motivation by suppressing the circuit.
“As we age, it’s harder to have a get-up-and-go
attitude toward things,” says Ann Graybiel, an Institute Professor at MIT and
member of the McGovern Institute for Brain Research. “This get-up-and-go, or
engagement, is important for our social well-being and for learning — it’s
tough to learn if you aren’t attending and engaged.”
Graybiel is the senior author of the study, which
appears today in Cell. The paper’s lead authors are
Alexander Friedman, a former MIT research scientist who is now an assistant
professor at the University of Texas at El Paso, and Emily Hueske, an MIT
research scientist.
Evaluating cost and benefit
The striatum is part of the basal ganglia — a
collection of brain centers linked to habit formation, control of voluntary
movement, emotion, and addiction. For several decades, Graybiel’s lab has been
studying clusters of cells called striosomes, which are distributed throughout
the striatum. Graybiel discovered striosomes many years ago, but their function
had remained mysterious, in part because they are so small and deep within the
brain that it is difficult to image them with functional magnetic resonance
imaging (fMRI).
In recent years, Friedman, Graybiel, and colleagues
including MIT research fellow Ken-ichi Amemori have discovered that striosomes
play an important role in a type of decision-making known as approach-avoidance
conflict. These decisions involve choosing whether to take the good with the
bad — or to avoid both — when given options that have both positive and
negative elements. An example of this kind of decision is having to choose
whether to take a job that pays more but forces a move away from family and
friends. Such decisions often provoke great anxiety.
In a related study, Graybiel’s lab found that
striosomes connect to cells of the substantia nigra, one of the brain’s major
dopamine-producing centers. These studies led the researchers to hypothesize
that striosomes may be acting as a gatekeeper that absorbs sensory and
emotional information coming from the cortex and integrates it to produce a
decision on how to act. These actions can then be invigorated by the
dopamine-producing cells.
The researchers later discovered that chronic stress
has a major impact on this circuit and on this kind of emotional
decision-making. In a 2017 study performed in rats and mice, they showed that
stressed animals were far more likely to choose high-risk, high-payoff options,
but that they could block this effect by manipulating the circuit.
In the new Cell study, the researchers
set out to investigate what happens in striosomes as mice learn how to make
these kinds of decisions. To do that, they measured and analyzed the activity
of striosomes as mice learned to choose between positive and negative outcomes.
During the experiments, the mice heard two different
tones, one of which was accompanied by a reward (sugar water), and another that
was paired with a mildly aversive stimulus (bright light). The mice gradually learned
that if they licked a spout more when they heard the first tone, they would get
more of the sugar water, and if they licked less during the second, the light
would not be as bright.
Learning to perform this kind of task requires
assigning value to each cost and each reward. The researchers found that as the
mice learned the task, striosomes showed higher activity than other parts of
the striatum, and that this activity correlated with the mice’s behavioral
responses to both of the tones. This suggests that striosomes could be critical
for assigning subjective value to a particular outcome.
“In order to survive, in order to do whatever you are
doing, you constantly need to be able to learn. You need to learn what is good
for you, and what is bad for you,” Friedman says.
“A person, or this case a mouse, may value a reward so
highly that the risk of experiencing a possible cost is overwhelmed, while
another may wish to avoid the cost to the exclusion of all rewards. And these
may result in reward-driven learning in some and cost-driven learning in
others,” Hueske says.
The researchers found that inhibitory neurons that
relay signals from the prefrontal cortex help striosomes to enhance their
signal-to-noise ratio, which helps to generate the strong signals that are seen
when the mice evaluate a high-cost or high-reward option.
Loss of motivation
Next, the researchers found that in older mice
(between 13 and 21 months, roughly equivalent to people in their 60s and
older), the mice’s engagement in learning this type of cost-benefit analysis
went down. At the same time, their striosomal activity declined compared to
that of younger mice. The researchers found a similar loss of motivation in a
mouse model of Huntington’s disease, a neurodegenerative disorder that affects
the striatum and its striosomes.
When the researchers used genetically targeted drugs
to boost activity in the striosomes, they found that the mice became more
engaged in performance of the task. Conversely, suppressing striosomal activity
led to disengagement.
In addition to normal age-related decline, many mental
health disorders can skew the ability to evaluate the costs and rewards of an
action, from anxiety and depression to conditions such as PTSD. For example, a
depressed person may undervalue potentially rewarding experiences, while
someone suffering from addiction may overvalue drugs but undervalue things like
their job or their family.
The researchers are now working on possible drug
treatments that could stimulate this circuit, and they suggest that training
patients to enhance activity in this circuit through biofeedback could offer
another potential way to improve their cost-benefit evaluations.
“If you could pinpoint a mechanism which is underlying
the subjective evaluation of reward and cost, and use a modern technique that
could manipulate it, either psychiatrically or with biofeedback, patients may
be able to activate their circuits correctly,” Friedman says.
Source: https://news.mit.edu/2020/why-learn-motivate-age-decline-1027
Source: https://myfusimotors.com/2020/10/29/study-helps-explain-why-motivation-to-learn-declines-with-age/
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