Study reveals set of brain regions that control complex sequences of
movement
Findings in mice have potential to advance treatment of some brain
injuries and illnesses

Date:
April 21, 2022
Source:
Johns Hopkins Medicine
Summary:
In a novel set of experiments with mice trained to do a sequence
of movements and 'change course' at the spur of the moment,
scientists report they have identified areas of the animals'
brains that interact to control the ability to perform complex,
sequential movements, as well as to help the mice rebound when
their movements are interrupted without warning.



FULL STORY ==========================================================================
In a novel set of experiments with mice trained to do a sequence of
movements and "change course" at the spur of the moment, Johns Hopkins scientists report they have identified areas of the animals' brains that interact to control the ability to perform complex, sequential movements,
as well as to help the mice rebound when their movements are interrupted without warning.


==========================================================================
The research, they say, could one day help scientists find ways to
target those regions in people and restore motor function caused by
injury or illness.

Results of the Johns Hopkins-led experiments were published March 9
in Nature.

Based on brain activity measurements of the specially trained rodents,
the investigators found that three main areas of the cortex have distinct
roles in how the mice navigate through a sequence of movements: the
premotor, primary motor and primary somatosensory areas. All are on
the top layers of the mammals' brains and arranged in a fundamentally
similar fashion in people.

The team concluded that the primary motor and primary somatosensory
areas are involved in controlling the immediate movements of the mice in
real time, while the premotor area appears to control an entire planned sequence of movements, as well as how the mice react and adjust when
the sequence is unexpectedly disrupted.

As the animals perform sequential movements, the researchers say,
it's likely that the premotor area sends electrical signals via special
nerve cells to the two other sensorimotor cortex areas, and more studies
are planned to chart the paths of those signals between and among the
cortical layers.



========================================================================== "Whether it's an Olympian practicing a downhill ski run or a person
doing an everyday chore such as driving, many tasks involve learned
sequences of movements made over and over," says Daniel O'Connor, Ph.D., associate professor of neuroscience at the Johns Hopkins University
School of Medicine. O'Connor led the research team. Such sequential
movements may seem commonplace and simple, he says, but they involve
complex organization and control in the brain, and the brain must not
only direct each movement correctly but also organize them into an entire series of linked movements.

When unexpected things happen to interrupt an ongoing sequence, O'Connor
says, the brain must adapt and direct the body to re-configure the
sequence in real time. Failure of this process can result in disaster --
a fall or car accident, for example.

Neuroscientists have long studied how mammals compensate when an
individual movement -- such as reaching for a coffee cup -- is disrupted,
but the new study was designed to address the challenges of tracking what happens when complex sequences of several movements must be reorganized
in real time to compensate for unexpected events.

In the case of the Olympic skier, for example, the skier expects to
perform a planned series of movements to approach and pass through gates
along a downhill run, but there will likely be moments when an obstacle disrupts the skier's trajectory and forces a change of course.

"How the mammalian brain can take a sensory cue and, almost instantly,
use it to completely switch from one ongoing sequence of movements to
another remains largely a mystery." O'Connor worked with Duo Xu, Ph.D.,
a former graduate student in O'Connor's laboratory, to design a set of experiments in mice to track the brain regions that process the "change
course" cue.



==========================================================================
For the study, the researchers first created a "course" for mice that
were trained to stick out their tongues and touch a "port" -- a metal
tube. When the investigators moved the port, the mice learned to touch
the port again. Over the span of the course, when the port was moved
to its final location, the mice that touched it with their tongues got
a reward. All of this training was meant to simulate a repeated and
expected sequence of learned movements, much as the skier's downhill run.

To study how an unexpected cue can prompt the brain to change course,
the researchers had the mice perform what scientists call a "backtracking trial." Instead of moving the port to the next in-sequence location,
the researchers moved the port to an earlier location, so that when the
mice extended their tongues, they failed to find the port, prompting
them to reverse course, find the port, and progress through the course
to get the treat.

"Each sequence of port licks involves a series of complex movements
that the mouse's brain needs to organize into a movement plan and then
perform correctly, but also to rapidly reorganize when they find that
the expected port isn't there," says O'Connor.

During the experiments, the researchers used brain electrodes to track
and record electrical signals among neurons in the sensorimotor cortex,
which controls overall movement. An increase in electrical activity
corresponds to increased brain activity. Because many areas of the
cortex could be activated when the mice moved through the course in the experiment, the researchers used mice bred with genetically engineered
brain cells that, in certain parts of the cortex, can be selectively
"silenced" or deactivated. Thus, the scientists could narrow down the
location of brain areas directly involved in the movements.

"The results provide a new picture of how a hierarchy among neural
networks in the sensorimotor cortex are managing sequential movements,"
says O'Connor. "The more we learn about these interacting neural networks,
the better positioned we are to understand sensorimotor dysfunction
in humans and how to correct it." In addition to Xu and O'Connor,
the following Johns Hopkins scientists contributed to the research:
Mingyuan Dong, Yuxi Chen, Angel Delgado, Natasha Hughes and Linghua Zhang.

The research was supported by the National Institutes of Health
(R01NS089652, 1R01NS104834-01, P30NS050274).


========================================================================== Story Source: Materials provided by Johns_Hopkins_Medicine. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Duo Xu, Mingyuan Dong, Yuxi Chen, Angel M. Delgado, Natasha
C. Hughes,
Linghua Zhang, Daniel H. O'Connor. Cortical processing of flexible
and context-dependent sensorimotor sequences. Nature, 2022; 603
(7901): 464 DOI: 10.1038/s41586-022-04478-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220421130946.htm

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