New prosthetic arm controlled by neural messages

This design hopes to identify the memory of movement in the amputee’s brain to translate to an order allowing manipulation of the device.

Controlling a prosthetic arm by just imagining a motion may be possible through the work of Mexican scientists at the Centre for Research and Advanced Studies (CINVESTAV), who work in the development of an arm replacement to identify movement patterns from brain signals.

First, it is necessary to know if there is a memory pattern to remember in the amputee’s brain in order to know how it moved and, thus, translating it to instructions for the prosthesis,” says Roberto Muñoz Guerrero, researcher at the Department of Electrical Engineering and project leader at Cinvestav.

He explains that the electric signal won’t come from the muscles that form the stump, but from the movement patterns of the brain. “If this phase is successful, the patient would be able to move the prosthesis by imagining different movements.”

However, Muñoz Guerrero acknowledges this is not an easy task because the brain registers a wide range of activities that occur in the human body and from all of them, the movement pattern is tried to be drawn. “Therefore, the first step is to recall the patterns in the EEG and define there the memory that can be electrically recorded. Then we need to evaluate how sensitive the signal is to other external shocks, such as light or blinking.”

Regarding this, it should be noted that the prosthesis could only be used by individuals who once had their entire arm and was amputated because some accident or illness. Patients were able to move the arm naturally and stored in their memory the process that would apply for the use of the prosthesis.

According to the researcher, the prosthesis must be provided with a mechanical and electronic system, the elements necessary to activate it and a section that would interpret the brain signals. “Regarding the material with which it must be built, it has not yet been fully defined because it must weigh between two and three kilograms, which is similar to the missing arm’s weight.”

The unique prosthesis represents a new topic in bioelectronics called BCI (Brain Computer Interface), which is a direct communication pathway between the brain and an external device in order to help or repair sensory and motor functions. “An additional benefit is the ability to create motion paths for the prosthesis, which is not possible with commercial products,” says Muñoz Guerrero.

How does the cerebellum work?

Nothing says “don’t mess with me” like a deeply-fissured cortex. Even the sharpest jaws and claws in the animal kingdom are worthless without some serious thought muscle under the hood. But beneath the highly convoluted membrane covering the brains of the evolutionary upper crust hides the original crumpled processor—the cerebellum. How this organ might actually work is the subject of a review published in Frontiers of Systems Neuroscience by researchers at the University of Minnesota.

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Scientists discover how to restore ability to grasp in paralysed hand

Pioneering research by scientists at a North East university could help people who have been paralysed to re-gain the use of their hands.

The researchers at Newcastle University have been able to restore the ability to grab objects with a paralysed hand using spinal cord stimulation.

The work, which has been funded by the Wellcome Trust, could help stroke and spinal injury victims as the research has shown that by connecting the brain to a computer and then the computer to the spinal cord, it is possible to restore movement.

The discovery opens up the possibility of new treatments within the next few years which could help stroke victims or those with spinal cord injuries regain some movement in their arms and hands as currently there is no cure for upper limb paralysis.

The work, led by Dr Andrew Jackson, Research Fellow at Newcastle University and Dr Jonas Zimmermann, now at Brown University in America, is published in the journal Frontiers in Neuroscience.

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Motor cortex shown to play active role in learning movement patterns

Skilled motor movements of the sort tennis players employ while serving a tennis ball or pianists use in playing a concerto, require precise interactions between the motor cortex and the rest of the brain. Neuroscientists had long assumed that the motor cortex functioned something like a piano keyboard.

"Every time you wanted to hear a specific note, there was a specific key to press," says Andrew Peters, a neurobiologist at UC San Diego’s Center for Neural Circuits and Behavior. "In other words, every specific movement of a muscle required the activation of specific cells in the motor cortex because the main job of the motor cortex was thought to be to listen to the rest of the cortex and press the keys it’s directed to press."

But in a study published in this week’s advance online publication of the journal Nature, Peters, the first author of the paper, and his colleagues found that the motor cortex itself plays an active role in learning new motor movements. In a series of experiments using mice, the researchers showed in detail how those movements are learned over time.

"Our finding that the relationship between body movements and the activity of the part of the cortex closest to the muscles is profoundly plastic and shaped by learning provides a better picture of this process," says Takaki Komiyama, an assistant professor of biology at UC San Diego who headed the research team. "That’s important, because elucidating brain plasticity during learning could lead to new avenues for treating learning and movement disorders, including Parkinson’s disease."

With Simon Chen, another UC San Diego neurobiologist, the researchers monitored the activity of neurons in the motor cortex over a period of two weeks while mice learned to press a lever in a specific way with their front limbs to receive a reward.

"What we saw was that during learning, different patterns of activity—which cells are active, when they’re active—were evident in the motor cortex," says Peters. "This ends up translating to different patterns of activity even for similar movements. Once the animal has learned the movement, similar movements are then accompanied by consistent activity. This consistent activity moreover is totally new to the animal: it wasn’t used early in learning even with movements that were similar to the later movement."

"Early on," Peters says, "the animals will occasionally make movements that look like the expert movements they make after learning. The patterns of brain activity that accompany those similar early and late movements are actually completely different though. Over the course of learning, the animal generates a whole new set of activity in the motor cortex to make that movement. In the piano keyboard analogy, that’s like using one key to make a note early on, but a different key to make the same note later."

Studies Identify Spinal Cord Neurons that Control Skilled Limb Movement

Researchers have identified two types of neurons that enable the spinal cord to control skilled forelimb movement. The first is a group of excitatory interneurons that are needed to make accurate and precise movements; the second is a group of inhibitory interneurons necessary for achieving smooth movement of the limbs. The findings are important steps toward understanding normal human motor function and potentially treating movement disorders that arise from injury or disease.

“We take for granted many motor behaviors, such as catching a ball or flipping a coin, that in fact require considerable planning and precision,” said Columbia University Medical Center’s (CUMC’s) Thomas M. Jessell, PhD, a senior author of both studies, which were published separately in recent issues of Nature (1, 2). “While such motor acts seem effortless, they depend on intricate and carefully orchestrated communication between neural networks that connect the brain to the spinal cord and muscles.”

To move one’s hand to a desired target, the brain sends the spinal cord signals, which activate the motor neurons that control limb muscles. During subsequent movements, information from the limb is conveyed back to the brain and spinal cord, providing a feedback system that can support the control and adjustment of motor output.

“But feedback from muscles is not quick enough to permit the most rapid real-time adjustments of fine motor control,” said Dr. Jessell, “suggesting that there may be other, faster, systems at play.” Dr. Jessell is the Claire Tow Professor of Motor Neuron Disorders in the Departments of Neuroscience and of Biochemistry and Molecular Biophysics, co-director of the Mortimer B. Zuckerman Mind Brain Behavior Institute, co-director of the Kavli Institute for Brain Science, and a Howard Hughes Medical Institute investigator, all at Columbia.

Researchers had suspected that one rapid form of feedback might derive from a group of interneurons in the cervical spinal cord called propriospinal neurons (PNs). Like many other neurons, PNs send signals to motor neurons that innervate arm muscles and trigger movement. But this subset of neurons also has a distinct output branch that projects away from motor neurons towards the cerebellum. Through this dual-branched anatomy, these neurons have the potential to carry internal copies of motor output signals up to the brain.

However, the nature of this internal feedback pathway and whether it has any impact on movement have not been clear. “If PNs were indeed sending copies of outgoing motor commands to the brain, they could provide a conveniently rapid means of adjusting ongoing movements when things go awry,” said Eiman Azim, PhD, a postdoctoral fellow in Dr. Jessell’s lab and lead author of the first paper. “But without a way to selectively target the copy function of PNs, there was no way to test this theory.”

The CUMC team, in collaboration with Bror Alstermark, PhD, a professor in integrative medical biology at Umeå University in Sweden, overcame this technical barrier by developing a genetic method for accessing and eliminating PNs in mice, abolishing both motor-directed and copy signals sent by the neurons. When the researchers quantified the limb movements of the PN-deprived mice in three dimensions as they reached for food pellets, they found that the mice’s ability to reach for the target accurately was badly compromised. “Basically, their movements were uncoordinated,” said Dr. Azim. “The PN-deprived mice consistently over- or under-reached.”

But with both PN output signals gone, the precise role of the PN copy signal remained unclear. The researchers then turned to optogenetics—the use of light to control neuronal activity. They selectively activated the copy axonal branch alone, decalibrating this copy signal from the version sent to motor neurons. With the copy signal altered, the animals’ ability to reach was severely compromised, indicating that the PN copy pathway is capable of influencing the outcome of goal-directed reaching movements.

The PN copy signal also works blazingly fast. It takes just 4 to 5 milliseconds for motor neuron activity to be altered after transmission of a PN copy signal. “These reaching movements typically take 200 to 300 milliseconds, so the PN copy signal pathway appears well equipped to correct arm movements,” said Dr. Azim. The researchers think that this copy signal represents just one of many similar internal feedback pathways that the spinal cord and brain use to validate and correct movements throughout the body.

Are these findings relevant to human motor performance? Many of the pathways and circuits that influence reach and grasp in monkeys and humans are conserved in mice. “We need to learn more about these pathways before we can evaluate how their dysfunction contributes to deficits seen after spinal cord injury and neurodegenerative disease,” said Dr. Azim.

In the second Nature study, CUMC researchers examined how spinal circuits regulate sensory feedback from muscles to control movement. The simplest form of this feedback system involves a reflex pathway (such as the knee-jerk reflex), in which sensory endings in muscles convey signals to the motor system through direct monosynaptic connections with motor neurons. Signals from motor neurons, in turn, cause muscles to contract, completing the reflex cycle.

Researchers have long wondered how the strength of this sensory signal might be regulated. Studies had shown that spinal interneurons—in particular those that release the neurotransmitter GABA, inhibiting neuronal activity—play a key role in this process. But most GABA-releasing interneurons exert their effects postsynaptically, by blocking the excitation of neurons on the receiving end of a synapse (the gap across which two neurons communicate).

“We knew that such neurons are unlikely to be responsible for fine-tuning the sensory signal,” said lead author Andrew J. P. Fink, PhD, a former graduate student in Dr. Jessell’s lab. “Postsynaptic inhibition affects the entire neuron, and motor neurons receive many different inputs. So a mechanism that shut down the motor neuron to all of its inputs would lack refinement.”

Researchers have long speculated that one subset of GABAergic interneurons might regulate movement by controlling the strength of sensory feedback signals from muscles. “These particular neurons are known to work presynaptically, by forming direct connections with the terminals of sensory neurons and suppressing the release of sensory neurotransmitter,” said Dr. Fink. For technical reasons, the function of these interneurons, if any, in motor behavior has remained elusive.

Dr. Fink and his colleagues identified a way to access this subset of interneurons genetically in mice and then devised approaches to manipulate their function in a selective manner. In one experiment, they activated presynaptic inhibitory interneurons optogenetically, decreasing the strength of sensory-motor transmission. They also ablated these interneurons by making them selectively sensitive to a lethal toxin, abolishing their control over sensory feedback strength. Without sensory feedback regulation, forelimb movements were dominated by severe oscillatory tremors, drastically diminishing motor accuracy.

This finding, along with parallel modeling studies, indicates that presynaptic inhibitory neurons normally adjust the “gain” of sensory feedback at synapses with motor neurons and are therefore crucial for the smooth execution of movement. Understanding how these basic microcircuits regulate sensory input and motor output may, in the long run, provide insight into ways to combat the movement instability and tremor seen in many neurological disorders.

“These two studies shed new light on how discrete classes of spinal interneurons empower the nervous system to direct motor behaviors in ways that match the particular task at hand,” said Dr. Jessell.

Muscle-controlling Neurons Know When They Mess Up

Whether it is playing a piano sonata or acing a tennis serve, the brain needs to orchestrate precise, coordinated control over the body’s many muscles. Moreover, there needs to be some kind of feedback from the senses should any of those movements go wrong. Neurons that coordinate those movements, known as Purkinje cells, and ones that provide feedback when there is an error or unexpected sensation, known as climbing fibers, work in close concert to fine-tune motor control.   

A team of researchers from the University of Pennsylvania and Princeton University has now begun to unravel the decades-spanning paradox concerning how this feedback system works.

At the heart of this puzzle is the fact that while climbing fibers send signals to Purkinje cells when there is an error to report, they also fire spontaneously, about once a second. There did not seem to be any mechanism by which individual Purkinje cells could detect a legitimate error signal from within this deafening noise of random firing. 

Using a microscopy technique that allowed the researchers to directly visualize the chemical signaling occurring between the climbing fibers and Purkinje cells of live, active mice, the Penn team has for the first time shown that there is a measurable difference between “true” and “false” signals.

This knowledge will be fundamental to future studies of fine motor control, particularly with regards to how movements can be improved with practice. 

The research was conducted by Javier Medina, assistant professor in the Department of Psychology in Penn’s School of Arts and Sciences, and Farzaneh Najafi, a graduate student in the Department of Biology. They collaborated with postdoctoral fellow Andrea Giovannucci and associate professor Samuel S. H. Wang of Princeton University.

It was published in the journal Cell Reports.

The cerebellum is one of the brain’s motor control centers. It contains thousands of Purkinje cells, each of which collects information from elsewhere in the brain and funnels it down to the muscle-triggering motor neurons. Each Purkinje cell receives messages from a climbing fiber, a type of neuron that extends from the brain stem and sends feedback about the associated muscles. 

“Climbing fibers are not just sensory neurons, however,” Medina said. “What makes climbing fibers interesting is that they don’t just say, ‘Something touched my face’; They say, ‘Something touched my face when I wasn’t expecting it.’ This is something that our brains do all the time, which explains why you can’t tickle yourself. There’s part of your brain that’s already expecting the sensation that will come from moving your fingers. But if someone else does it, the brain can’t predict it in the same way and it is that unexpectedness that leads to the tickling sensation.”

Not only does the climbing fiber feedback system for unexpected sensations serve as an alert to potential danger — unstable footing, an unseen predator brushing by — it helps the brain improve when an intended action doesn’t go as planned.    

“The sensation of muscles that don’t move in the way the Purkinje cells direct them to also counts as unexpected, which is why some people call climbing fibers ‘error cells,’” Medina said. “When you mess up your tennis swing, they’re saying to the Purkinje cells, ‘Stop! Change! What you’re doing is not right!’ That’s where they help you learn how to correct your movements.

“When the Purkinje cells get these signals from climbing fibers, they change by adding or tweaking the strength of the connections coming in from the rest of the brain to their dendrites. And because the Purkinje cells are so closely connected to the motor neurons, the changes to those synapses are going to result in changes to the movements that Purkinje cell controls.”

This is a phenomenon known as neuroplasticity, and it is fundamental for learning new behaviors or improving on them. That new neural pathways form in response to error signals from the climbing fibers allows the cerebellum to send better instructions to motor neurons the next time the same action is attempted.

The paradox that faced neuroscientists was that these climbing fibers, like many other neurons, are spontaneously activated. About once every second, they send a signal to their corresponding Purkinje cell, whether or not there were any unexpected stimuli or errors to report.

“So if you’re the Purkinje cell,” Medina said, “how are you ever going to tell the difference between signals that are spontaneous, meaning you don’t need to change anything, and ones that really need to be paid attention to?”

Medina and his colleagues devised an experiment to test whether there was a measurable difference between legitimate and spontaneous signals from the climbing fibers. In their study, the researchers had mice walk on treadmills while their heads were kept stationary. This allowed the researchers to blow random puffs of air at their faces, causing them to blink, and to use a non-invasive microscopy technique to look at how the relevant Purkinje cells respond.

The technique, two-photon microscopy, uses an infrared laser and a reflective dye to look deep into living tissue, providing information on both structure and chemical composition. Neural signals are transmitted within neurons by changing calcium concentrations, so the researchers used this technique to measure the amount of calcium contained within the Purkinje cells in real time.

Because the random puffs of air were unexpected stimuli for the mice, the researchers could directly compare the differences between legitimate and spontaneous signals in the eyelid-related Purkinje cells that made the mice blink.

“What we have found is that the Purkinje cell fills with more calcium when its corresponding climbing fiber sends a signal associated with that kind of sensory input, rather than a spontaneous one,” Medina said. “This was a bit of a surprise for us because climbing fibers had been thought of as ‘all or nothing’ for more than 50 years now.”

The mechanism that allows individual Purkinje cells to differentiate between the two kinds of climbing fiber signals is an open question. These signals come in bursts, so the number and spacing of the electrical impulses from climbing fiber to Purkinje cell might be significant. Medina and his colleagues also suspect that another mechanism is at play: Purkinje cells might respond differently when a signal from a climbing fiber is synchronized with signals coming elsewhere from the brain.   

Whether either or both of these explanations are confirmed, the fact that individual Purkinje cells are able to distinguish when their corresponding muscle neurons encounter an error must be taken into account in future studies of fine motor control. This understanding could lead to new research into the fundamentals of neuroplasticity and learning.    

“Something that would be very useful for the brain is to have information not just about whether there was an error but how big the error was — whether the Purkinje cell needs to make a minor or major adjustment,” Medina said. “That sort of information would seem to be necessary for us to get very good at any kind of activity that requires precise control. Perhaps climbing fiber signals are not as ‘all-or-nothing’ as we all thought and can provide that sort of graded information”