CC to the brain: How neurons control fine motor behavior of the arm

Motor commands issued by the brain to activate arm muscles take two different routes. As the research group led by Professor Silvia Arber at the Basel University Biozentrum and the Friedrich Miescher Institute for Biomedical Research has now discovered, many neurons in the spinal cord send their instructions not only towards the musculature, but at the same time also back to the brain via an exquisitely organized network. This dual information stream provides the neural basis for accurate control of arm and hand movements. These findings have now been published in “Cell”.

Movement is a fundamental capability of humans and animals, involving the highly complex interplay of brain, nerves and muscles. Movements of our arms and hands, in particular, call for extremely precise coordination. The brain sends a constant stream of commands via the spinal cord to our muscles to execute a wide variety of movements. This stream of information from the brain reaches interneurons in the spinal cord, which then transmit the commands via further circuits to motor neurons innervating muscles. The research group led by Silvia Arber at the Biozentrum of the University of Basel and the Friedrich Miescher Institute for Biomedical Research has now elucidated the organization of a second information pathway taken by these commands.

cc to the brain: one command – two directions

The scientists showed that many interneurons in the mouse spinal cord not only transmit their signals via motor neurons to the target muscle, but also simultaneously send a copy of this information back to the brain. Chiara Pivetta, first author of the publication, explains: “The motor command to the muscle is sent in two different directions – in one direction, to trigger the desired muscular contraction and in the other, to inform the brain that the command has actually been passed on to the musculature.” In analogy to e‑mail transmission, the information is thus not only sent to the recipient but also to the original requester.

Information to brainstem nucleus segregated by function

What happens to the information sent by spinal interneurons to the brain? As Arber’s group discovered, this input is segregated by function and spatially organized within a brainstem nucleus. Information from different types of interneurons thus flows to different areas of the nucleus. For example, spinal information that will influence left-right coordination of a movement is collected at a different site than information affecting the speed of a movement.

Fine motor skills supported by dual information stream

Arber comments: “From one millisecond to the next, this extremely precise feedback ensures that commands are correctly transmitted and that – via the signals sent back to the brain from the spinal cord – the resulting movement is immediately coordinated with the brain and adjusted.” Interestingly, the scientists only observed this kind of information flow to the brain for arm, but not for leg control. “What this shows,” says Arber, “is that this information pathway is most likely important for fine motor skills. Compared to the leg, movements of our arm and especially our hands have to be far more precise. Evidently, our body can only ensure this level of accuracy in motor control with constant feedback of information.”

In further studies, Silvia Arber’s group now plans to investigate what happens if the flow of information back to the brain is disrupted in specific ways. Since some interneurons facilitate and others inhibit movement, such studies could provide additional insights into the functionality of circuits controlling movement.

Researchers reveal more about how our brains control our arms

Ready, set, go.

Sometimes that’s how our brains work. When we anticipate a physical act, such as reaching for the keys we noticed on the table, the neurons that control the task adopt a state of readiness, like sprinters bent into a crouch.

Other times, however, our neurons must simply react, such as if someone were to toss us the keys without gesturing first, to prepare us to catch.

How do the neurons in the brain control planned versus unplanned arm movements?

Krishna Shenoy, a Stanford professor of electrical engineering, neurobiology (by courtesy) and bioengineering (affiliate), wanted to answer that question as part of his group’s ongoing efforts to develop and improve brain-controlled prosthetic devices.

In a paper published today in the journal Neuron, Shenoy and first author Katherine Cora Ames, a doctoral student in the Neurosciences Graduate Program, present a mathematical analysis of the brain activity of monkeys as they make anticipated and unanticipated reaching motions.

Monitoring the neurons

The experimental data came from recording the electrical activity of neurons in the brain that control motor and premotor functions. The idea was to observe and understand the activity levels of these neurons during experiments in which the monkeys made planned or reactive arm movements. What the researchers found is that when the monkeys knew what arm movement they were supposed to make and were simply waiting for the cue to act, electrical readings showed that the neurons went into what scientists call the prepare-and-hold state – the brain’s equivalent of ready, set, waiting for the cue to go.

But when the monkeys made unplanned or unexpected movements, the neurons did not go through the expected prepare-and-hold state. “This was a surprise,” Ames said.

Before the experiment, the researchers had believed that a prepare-and-hold state had to precede movement. In short, they thought the neurons had to go into a “ready, set” crouch before acting on the “go” command. But they discovered otherwise in three variations of an experiment involving similar arm movements.

Experimental design

In all three cases, the monkeys were trained to touch a target that appeared on a display screen.

During each motion, the researchers measured the electrical activity of the neurons in control of arm movements.

In one set of experiments, the monkeys were shown the target but were trained not to touch it until they got the “go” signal. This is called a delayed reach experiment. It served as the planned action.

In a second set of experiments the monkeys were trained to touch the target as soon as it appeared. This served as the unplanned action.

In a third variant, the position of the target was changed. It briefly appeared in one location on the screen. The target then reappeared in a different location. This required the monkeys to revise their movement plan.

Monkey see, then monkey do

Ames said that, in all three instances, the first information to reach the neurons was awareness of the target.

“Perception always occurred first,” Ames said.

Then, about 50 milliseconds later, some differences appeared in the data. When the monkeys had to wait for the go command, the brain recordings showed that the neurons went into a discernable prepare-and-hold state. But in the other two cases, the neurons did not enter the prepare-and-hold state.

Instead, roughly 50 milliseconds after the electrical readings showed evidence of perception, a change in neuronal activity signaled the command to touch the target; it came with no apparent further preparation between perception and action. “Ready, set” was unnecessary. In these instances, the neurons just said, “Go!”

Applications

“This study changes our view of how movement is controlled,” Ames said. “First you get the information about where to move. Then comes the decision to move. There is no specific prepare-and-hold stage unless you are waiting for the signal to move.”

These nuanced understandings are important to Shenoy. His lab develops and improves electronic systems that can convert neural activity into electronic signals in order to control a prosthetic arm or move the cursor on a computer screen.

One example of such efforts is the BrainGate clinical trial here at Stanford, now being conducted under U.S. Food & Drug Administration supervision, to test the safety of brain-controlled, computer cursor systems – “think-and-click” communication for people who can’t move.

“In addition to advancing basic brain science, these new findings will lead to better brain-controlled prosthetic arms and communication systems for people with paralysis,” Shenoy said.