Researchers identify areas of the brain that control the ability to perform complex, sequential movements

In a new series of experiments with mice trained to perform a sequence of movements and “change course” on the spur of the moment, Johns Hopkins scientists report that they have identified areas of the animals’ brains that interact to control the ability to perform complex actions, sequential movements, as well as to help mice bounce back when their movements are interrupted without warning.

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

The results of the experiments conducted by Johns Hopkins were published on March 9 in Nature.

Based on measurements of the brain activity of the specially trained rodents, the researchers 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. All are found on the upper layers of the mammalian brain and are arranged basically similarly in humans.

The team concluded that the primary motor and primary somatosensory areas are involved in controlling the mice’s immediate movements in real time, while the premotor area appears to control a whole planned sequence of movements, as well as how the mice react. and adapt when the sequence is unexpectedly interrupted.

As the animals perform sequential movements, the researchers say, it is likely that the premotor area sends electrical signals via special nerve cells to the other two areas of the sensorimotor cortex, and further studies are planned to trace the pathways of these signals. between and among the cortical layers. .

Whether it’s an Olympian downhill skiing or someone performing an everyday task such as driving, many tasks involve learned sequences of movements repeated over and over.”

Daniel O’Connor, Ph.D., Associate Professor of Neuroscience, Johns Hopkins University School of Medicine

O’Connor led the search team. Such sequential movements may seem mundane and simple, he says, but they involve complex organization and control in the brain, and the brain must not only properly direct each movement, but also organize them into an entire series of linked movements.

When unexpected events interrupt an ongoing sequence, O’Connor explains, the brain must adapt and direct the body to reconfigure the sequence in real time. Failure in this process can lead to a disaster – a fall or a car accident, for example.

Neuroscientists have long studied how mammals compensate when an individual movement – like reaching for a cup of coffee – is disrupted, but the new study was designed to address the challenges of tracking what happens when complex sequences of multiple movements have to be rearranged 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 descent, but there will likely be times when an obstacle interferes the skier’s trajectory and forces a change of trajectory. Classes.

“How the mammalian brain can take a sensory cue and, almost instantaneously, use it to switch completely from one ongoing movement sequence to another remains largely a mystery.” O’Connor worked with Duo Xu, Ph.D., a former graduate student in O’Connor’s lab, to design a set of experiments in mice to track brain regions that process the signal to “change heading”.

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 it again. Along the way, when the port was moved to its final location, mice that touched it with their tongues got a reward. All of this training was aimed at simulating a repeated and expected sequence of learned movements, much like the skier’s descent.

To study how an unexpected signal can trick the brain into changing course, the researchers asked mice to perform what scientists call a “flashback trial.” Instead of moving the port to the next location in the sequence, 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 backtrack, find the port, and progress through the course to get the treat.

“Each port-licking sequence involves a series of complex movements that the mouse brain needs to organize a plane of movement and then perform correctly, but also to quickly rearrange itself when they find that the expected port is not there,” says O’Connor. .

During the experiments, the researchers used brain electrodes to track and record electrical signals between neurons in the sensorimotor cortex, which controls overall movement. An increase in electrical activity corresponds to increased brain activity. Since many areas of the cortex could be activated when the mice went through the course of the experiment, the researchers used mice bred with genetically modified brain cells that in certain parts of the cortex can be selectively “silent” or deactivated. Thus, the scientists were able to refine the location of the brain areas directly involved in movement.

“The results provide a new picture of how a hierarchy between neural networks in the sensorimotor cortex manages sequential movements,” says O’Connor. “The more we learn about these interacting neural networks, the better we are at understanding sensorimotor dysfunction in humans and how to correct it.””>


Journal reference:

Xu, D. et al. (2022) Cortical processing of flexible and context-dependent sensorimotor sequences. Nature.

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