Neuroscience

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Posts tagged motor control

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Scientists reveal circuitry of fundamental motor circuit

Scientists at the Salk Institute have discovered the developmental source for a key type of neuron that allows animals to walk, a finding that could help pave the way for new therapies for spinal cord injuries or other motor impairments related to disease.

The spinal cord contains a network of neurons that are able to operate largely in an autonomous manner, thus allowing animals to carry out simple rhythmic walking movements with minimal attention—giving us the ability, for example, to walk while talking on the phone. These circuits control properties such as stepping with each foot or pacing the tempo of walking or running.

The researchers, led by Salk professor Martyn Goulding, identified for the first time which neurons in the spinal cord were responsible for controlling a key output of this locomotion circuit, namely the ability to synchronously activate and deactivate opposing muscles to create a smooth bending motion (dubbed flexor-extensor alternation). The findings were published April 2 in Neuron.

Motor circuits in the spinal cord are assembled from six major types of interneurons—cells that interface between nerves descending from the brain and nerves that activate or inhibit muscles. Goulding and his team had previously implicated one class of interneuron, the V1 interneurons, as being a likely key component of the flexor-extensor circuitry. However when V1 interneurons were removed, the team saw that flexor-extensor activity was still intact, leading them to suspect another type of cell was also involved in coordinating this aspect of movement.

To determine what other interneurons were at play in the flexor-extensor circuit, the team looked for other cells in the spinal cord with properties that were similar to those of the V1 neurons. In doing this they began to focus on another class of neuron, whose function was not known, V2b interneurons. Using a specialized experimental setup that allows one to monitor locomotion in the spinal cord itself, the team saw a synchronous pattern of flexor and extensor activity when V2b interneurons were inactivated along with the V1 interneurons.

The team also showed that this synchronicity led to newborn mice displaying a tetanus-like reaction when the two types of interneurons were inactivated: the limbs froze in one position because they no longer had the push-pull balance of excitation and inhibition that is needed to move.

These findings further confirm the hypothesis put forward over 120 years ago by the Nobel Prize-winning neuroscientist, Charles Sherrington, that flexor-extensor alternation is essential for locomotion in all animals that have limbs. He proposed that specialized cells in the spinal cord called switching cells performed this function. After 120 years, Goulding and researchers have now uncovered the identity of these switching cells.

"Our whole motor system is built around flexor-extension; this is the cornerstone component of movement," says Goulding, holder of Salk’s Frederick W. and Joanna J. Mitchell Chair. "If you really want to understand how animals move you need to understand the contribution of these switching cells."

With a more thorough understanding of the basic science around how this flexor-extensor circuit works, scientists will be in a better position to, for example, create a system that can reactivate the spinal cord or mimic signals sent from the brain to the spinal cord.

Filed under interneurons motor control motor movement spinal cord neuroscience science

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Brain scans show what makes us drink water and what makes us stop drinking
Drinking water when you’re thirsty is a pleasurable experience. Continuing to drink when you’re not, however, can be very unpleasant. To understand why your reaction to water drinking changes as your thirst level changes, Pascal Saker of the University of Melbourne and his colleagues performed fMRI scans on people as they drank water. They found that regions of the brain associated with positive feelings became active when the subjects were thirsty, while regions associated with negative feelings and with controlling and coordinating movement became active after the subjects were satiated. The research appears in the Proceedings of the National Academy of Sciences.
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Brain scans show what makes us drink water and what makes us stop drinking

Drinking water when you’re thirsty is a pleasurable experience. Continuing to drink when you’re not, however, can be very unpleasant. To understand why your reaction to water drinking changes as your thirst level changes, Pascal Saker of the University of Melbourne and his colleagues performed fMRI scans on people as they drank water. They found that regions of the brain associated with positive feelings became active when the subjects were thirsty, while regions associated with negative feelings and with controlling and coordinating movement became active after the subjects were satiated. The research appears in the Proceedings of the National Academy of Sciences.

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Filed under brain scans drinking water cingulate cortex orbitofrontal cortex motor control neuroscience science

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No Clowning Around: Juggling Study May Shed Light on How Our Senses Help Us Run

Juggling may sound like mere entertainment, but a study led by Johns Hopkins engineers has used this circus skill to gather critical clues about how vision and the sense of touch help control the way humans and animals move their limbs in a repetitive way, such as in running. The findings eventually may aid in the treatment of people with neurological diseases and could lead to prosthetic limbs and robots that move more efficiently.

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The study was published online recently by the Journal of Neurophysiology and is the cover article in the journal’s March 2014 print edition.

In their paper, the team led by Johns Hopkins researchers detailed the unusual jump from juggling for fun to serious science. Jugglers, they explained, rely on repeated rhythmic motions to keep multiple balls aloft. Similar forms of rhythmic movement are also common in the animal world, where effective locomotion is equally important to a swift-moving gazelle and to the cheetah that’s chasing it.

“It turns out that the art of juggling provides an interesting window into many of the same questions that you try to answer when you study forms of locomotion, such as walking or running,” said Noah Cowan, an associate professor of mechanical engineering who supervised the research. “In our study, we had participants stand still and use their hands in a rhythmic way. It’s very much like watching them move their feet as they run. But we used juggling as a model for rhythmic motor coordination because it’s a simpler system to study.”

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Filed under juggling vision haptics locomotion motor control neuroscience science

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Going from Good to Great with Complex Tasks

It is a common belief that consciously thinking about what we are doing interferes with our performance. The origins of this idea go far back. Consider, for instance, the centipede’s dilemma:

A centipede was happy – quite!
Until a toad in fun
Said, “Pray, which leg moves after which?”
This raised her doubts to such a pitch,
She fell exhausted in the ditch
Not knowing how to run. 

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The centipede performs a very complex task with ease, unless she thinks about the task. The story was thought to illustrate something fundamental about human nature. English psychologist George Humphrey wrote “[the poem] contains a profound truth which is illustrated daily in the lives of all of us.” Humphrey and others thought that not having to think about everything that we do provides a great advantage. According to the famed philosopher Alfred North Whitehead, “Civilization advances by extending the number of important operations which we can perform without thinking about them.” Whitehead believed that thinking must be reserved only for decisive moments.

Though common, this idea is misleading. It is never optimal to run on autopilot. Even the motor tasks that we have learned to do fluently without much cognitive control are better performed while engaged. The key is to realize that we can apply cognitive control at a higher level. Moreover, gaining fluency at a motor task often comes at a cost. The cost is rigidity and deliberately breaking the flow in response to changing contexts often pays off. Musicians, athletes, public speakers, architects, designers, and others whose jobs require complex sequential actions can increase their performance if they understand that they are not trapped in the centipede’s dilemma.  

In a fascinating paper, Brain researchers Eitan Globerson and Israel Nelken started with the observation that piano playing involves a very complex sequential motor task. The task is often executed in speeds that do not allow cognitive control of individual muscle movements. Through practice, pianists learn to execute fast and complex motor tasks with little cognitive control. Once this is achieved, it is possible to play in a disengaged way with little cognitive involvement. However, Globerson and Nelken suggest another way. Instead of focusing on individual finger movements or not focusing on anything, pianists may focus on higher-level mental events, such as the character of a longer musical phrase. This allows constant engagement with the music making and deliberate control without disrupting the mechanics of playing. Globerson and Nelken argue that this may dramatically improve performance.

If we follow their argument, it is easy to come up with our own examples about how to use higher-level cognitive control. While playing, a pianist may actively focus on the relationships between different musical ideas. A public speaker may develop a “mental script” that includes bigger-picture ideas, the connections between those ideas, where the climax of the speech should be, and what general effects should the speech make on the audience. During the speech, the public speaker may be constantly engaged with this mental script instead of trying to select words individually or mechanically replicating a previous performance. While shooting, a basketball player may focus on the arc that the ball should follow instead of focusing on arm movements or focusing on nothing. You can create your own examples of higher-level cognitive control for dancing, driving a car, designing a house, or doing the work of a carpenter.

Experts have long been aware of the power of focusing on higher-level mental processes. In 1924, Russian pianist and piano teacher Josef Lhevinne wrote the book Basic Principles in Pianoforte Playing, which later became a classic. In his discussion of memory, he wrote, “the thing to remember is the thought, not the symbols. When you remember a poem you do not remember the alphabetical symbols, but the poet’s beautiful vision, his thought pictures. … Get the thought, the composer’s idea; that is the thing that sticks.”

Higher-level cognitive control is capable of changing the motor action in a beneficial way. When a pianist decides to play a passage in an expressive fashion, for instance, this high-level command changes the character of playing through initiating a sequence of associated motor movements. There is experimental evidence that suggests that performance in highly automatized tasks can be improved by increasing the level of engagement. Musicians in symphony orchestras are typically asked to play the same pieces many times over the course of their careers. The playing of these pieces becomes mostly automatic; and the job satisfaction of orchestra players is typically dismal. Psychologists Ellen Langer, Timothy Russell, and Noah Eisenkraft recently asked a symphony orchestra to record, under different experimental conditions, the finale from Brahms’s Symphony No. 1. A local community chorus listened to and rated the recordings. The musicians were either asked to replicate a previous fine performance or to offer “subtle new nuances” to their performance. Musicians enjoyed the latter performance more; and the majority of the listeners preferred the recording of the latter performance.

There is always an unconscious component of the link between our intentions and the motor actions those intentions create. Even if I deliberately stretch my arm to grab a coffee mug, I do not have conscious control over the way the individual muscles in my arm operate to give rise to the specific stretching movement. Deliberate cognitive control is always less complex than the actual motor action. However, we often learn to apply cognitive control in an even more summary-like way. That is, we can learn to apply cognitive control in a single step over longer and more complex sequences of motor actions. Through practice, sequences of motor actions merge into a single unit that can be initiated by a single deliberate command. This is often called chunking. When children first learn how to brush their teeth or lace their shoes, they deliberately control individual movements that make up the task. After some practice, the individual movements are chunked and the whole sequence can be initiated by a single mental command. Many other daily activities such as riding a bike or writing one’s signature involve chunking. It is possible to merge chunked sequences into even longer sequences and reduce cognitive involvement even more.

Once initiated, a chunked motor sequence is executed automatically. As a consequence, we lose control over individual movements. This type of rigidity is often undesirable because we live in a constantly changing environment. In her book The Power of Mindful Learning Harvard psychologist Ellen Langer talks about how automaticity may get in the way of adapting to new circumstances. Overlearned driving skills may put one in danger while driving in a different country or in different weather conditions. Holding a baseball bat in the same overlearned way after getting older or stronger will hinder performance.

We can disrupt automaticity and appropriately respond to the situation at hand by orienting ourselves in the present and being sensitive to different contexts. We can think at a level higher than the mechanics of the motor action. We can be engaged with the task by making use of these two approaches simultaneously. In any case, thinking should never be reserved.

Filed under music performance motor control cognitive control automaticity neuroscience science

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Motor Control Development Continues Longer Than Previously Believed

Research opens up longer therapy window for children with neurodevelopmental disorders

The development of fine motor control – the ability to use your fingertips to manipulate objects – takes longer than previously believed, and isn’t entirely the result of brain development, according to a pair of complementary studies.

The research opens up the potential to use therapy to continue improving the motor control skills of children suffering from neurodevelopmental disorders such as cerebral palsy, a blanket term for central motor disorders that affects about 764,000 children and adults nationwide.

“These findings show that it’s not only possible, but critical to continue or begin physical therapy in adolescence,” said Francisco Valero-Cuevas, corresponding author of two studies on the matter – one appearing in the Journal of Neurophysiology and the other in the Journal of Neuroscience.

“We find we likely do not have a narrow window of opportunity in early childhood to improve manipulation skills, as previously believed, but rather developmental plasticity lasts much longer and provides opportunity throughout adolescence” he said. “This complements similarly exciting findings showing brain plasticity in adulthood and old age.”

Researchers had previously been able to detect improvements in fine motor control of the hand only until around ages 8-10. However, Valero-Cuevas – a professor of biomedical engineering and of biokinesiology and physical therapy – invented a tool that allows for more precise measurement of fine motor control.

The tool is simple – springs of varying stiffness and length set between plastic pads which Valero-Cuevas has patented. Motor skill is then determined by the individual’s ability to compress the increasingly awkward spring devices. Sudarshan Dayanidhi, during his PhD studies at USC with Valero-Cuevas, developed and applied clinically useful versions of this technology with great success.

With this new tool, and in collaboration with Åsa Hedberg and Hans Forssberg of the Astrid Lindgren Children’s Hospital in Stockholm, they tested 130 children with typical development between 4-16 years of age, and demonstrated that even the 16-year-olds were continuing to hone their fine motor skills. Their findings will appear in the Journal of Neurophysiology on Oct. 1.

To further this study, Dayanidhi and Valero-Cuevas joined forces with Assistant Professor of biokinesiology and physical therapy Jason Kutch (also of USC), to explore if this longer developmental timeline for dexterity was tied not just to brain maturation, but also to muscular development.

It has long been thought that improved dexterity involved only brain development and muscle growth – where muscles only got bigger and stronger – but did not add to dexterous skills since they are performed at low forces. The research by Dayanidhi, Kutch and Valero-Cuevas indicates otherwise.

“Combining our metrics of dexterity from Dayanidhi’s PhD work, with novel and noninvasive measures of muscle contraction time developed by Prof. Kutch, we were able to show a previously unknown strong association between gains in dexterity with improvement in low force muscle contraction time,” Valero-Cuevas said.

This second facet of the research showing how both dexterity and muscle function improve in children will appear in the Journal of Neuroscience on Sept. 18.

(Source: pressroom.usc.edu)

Filed under neurodevelopmental disorders motor control plasticity cerebral palsy neuroscience science

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Movement without muscles study in insects could inspire robot and prosthetic limb developments 
Neurobiologists from the University of Leicester have shown that insect limbs can move without muscles – a finding that may provide engineers with new ways to improve the control of robotic and prosthetic limbs.
Their work helps to explain how insects control their movements using a close interplay of neuronal control and ‘clever biomechanical tricks,’ says lead researcher Dr Tom Matheson, a Reader in Neurobiology at the University of Leicester.
In a study published today in the journal Current Biology, the researchers show that the structure of some insect leg joints causes the legs to move even in the absence of muscles. So-called ‘passive joint forces’ serve to return the limb back towards a preferred resting position.
The passive movements differ in limbs that have different behavioural roles and different musculature, suggesting that the joint structures are specifically adapted to complement muscle forces. The researchers propose a motor control scheme for insect limb joints in which not all movements are driven by muscles.
The study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), The Royal Society, and the Heinrich Hertz-Foundation of the German State of North Rhine-Westphalia.
Dr Matheson, of the Department of Biology, said:
“It is well known that some animals store energy in elastic muscle tendons and other structures. Such energy storage permits forces to be applied explosively to generate movements that are much more rapid than those which may be generated by muscle contractions alone. This is, for example, crucial when grasshoppers or fleas jump.
“This University of Leicester study provides a new insight into the ways that energy storage mechanisms can operate in a much wider range of movements.
“Our work set out to identify how the biomechanical properties of the limbs of a range of insects influence relatively slow movements such as those that occur during walking, scratching or climbing. The surprising result was that although some movements are influenced by properties of the muscles and tendons, other movements are generated by forces that arise from within the joints themselves.
“Even when we removed all of the muscles and associated tissues from a particular joint at the ‘knee’ of a locust, the lower part of the limb (the tibia) still moved back towards a midpoint from extended angles.”
Dr Matheson said that it was known from previous studies that some movements can be generated by spring-like properties of limbs, but the team was surprised to find passive forces that contribute to almost all movements made by the limbs that were studied - not just the highly specialised rapid movements needed to propel powerful jumps and kicks.
“We expected the forces to be generated within the muscles of the leg, but found that some continued to occur even when we detached both muscles – the extensor and the flexor tibiae – from the tibia.
“In the locust hind leg, which is specialised for jumping and kicking, the extensor muscle is much larger and stronger than the antagonist flexor muscle. This enables the animal to generate powerful kicks and jumps propelled by extensions of the tibia that are driven by contractions of the extensor muscle. When locusts prepare to jump, large amounts of energy generated by the extensor muscle are stored in the muscle’s tendon and in the hard exoskeleton of the leg.
“Surprisingly, we noticed that when the muscles were removed, the tibia naturally flexed back towards a midpoint, and we hypothesised that these passive return movements might be counterbalancing the strong extensor muscle.”
Jan M. Ache, a Masters student from the Department of Animal Physiology at the University of Cologne who worked in Matheson’s lab and is the first author on the paper, continues: “To test this idea we looked at the literature and examined other legs where the extensor and flexor muscles are more closely balanced in size or strength, or where the flexor is stronger than the extensor.
“We found that the passive joint forces really do counterbalance the stronger of the flexor or extensor muscle in the animals and legs we looked at. In the horsehead grasshopper, for example, passive joint forces even differ between the middle legs (which are primarily used for walking) and the hind legs (which are adapted for jumping), even in the same individual animal. In both pairs of legs, the passive joint forces support the weaker muscle.
“This could be very important for the generation of movements in insects because the passive forces enable a transfer of energy from the stronger to the weaker muscle.”
This work helps to explain how insects control their movements using a close interplay of neuronal control and clever biomechanical tricks. Using balanced passive forces may provide engineers with new ways to improve the control of robotic and prosthetic limbs, say the researchers.
Dr Matheson concluded: “We hope that our work on locusts and grasshoppers will spur a new understanding of how limbs work and can be controlled, by not just insects, but by other animals, people, and even by robots.”

Movement without muscles study in insects could inspire robot and prosthetic limb developments

Neurobiologists from the University of Leicester have shown that insect limbs can move without muscles – a finding that may provide engineers with new ways to improve the control of robotic and prosthetic limbs.

Their work helps to explain how insects control their movements using a close interplay of neuronal control and ‘clever biomechanical tricks,’ says lead researcher Dr Tom Matheson, a Reader in Neurobiology at the University of Leicester.

In a study published today in the journal Current Biology, the researchers show that the structure of some insect leg joints causes the legs to move even in the absence of muscles. So-called ‘passive joint forces’ serve to return the limb back towards a preferred resting position.

The passive movements differ in limbs that have different behavioural roles and different musculature, suggesting that the joint structures are specifically adapted to complement muscle forces. The researchers propose a motor control scheme for insect limb joints in which not all movements are driven by muscles.

The study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), The Royal Society, and the Heinrich Hertz-Foundation of the German State of North Rhine-Westphalia.

Dr Matheson, of the Department of Biology, said:

“It is well known that some animals store energy in elastic muscle tendons and other structures. Such energy storage permits forces to be applied explosively to generate movements that are much more rapid than those which may be generated by muscle contractions alone. This is, for example, crucial when grasshoppers or fleas jump.

“This University of Leicester study provides a new insight into the ways that energy storage mechanisms can operate in a much wider range of movements.

“Our work set out to identify how the biomechanical properties of the limbs of a range of insects influence relatively slow movements such as those that occur during walking, scratching or climbing. The surprising result was that although some movements are influenced by properties of the muscles and tendons, other movements are generated by forces that arise from within the joints themselves.

“Even when we removed all of the muscles and associated tissues from a particular joint at the ‘knee’ of a locust, the lower part of the limb (the tibia) still moved back towards a midpoint from extended angles.”

Dr Matheson said that it was known from previous studies that some movements can be generated by spring-like properties of limbs, but the team was surprised to find passive forces that contribute to almost all movements made by the limbs that were studied - not just the highly specialised rapid movements needed to propel powerful jumps and kicks.

“We expected the forces to be generated within the muscles of the leg, but found that some continued to occur even when we detached both muscles – the extensor and the flexor tibiae – from the tibia.

“In the locust hind leg, which is specialised for jumping and kicking, the extensor muscle is much larger and stronger than the antagonist flexor muscle. This enables the animal to generate powerful kicks and jumps propelled by extensions of the tibia that are driven by contractions of the extensor muscle. When locusts prepare to jump, large amounts of energy generated by the extensor muscle are stored in the muscle’s tendon and in the hard exoskeleton of the leg.

“Surprisingly, we noticed that when the muscles were removed, the tibia naturally flexed back towards a midpoint, and we hypothesised that these passive return movements might be counterbalancing the strong extensor muscle.”

Jan M. Ache, a Masters student from the Department of Animal Physiology at the University of Cologne who worked in Matheson’s lab and is the first author on the paper, continues: “To test this idea we looked at the literature and examined other legs where the extensor and flexor muscles are more closely balanced in size or strength, or where the flexor is stronger than the extensor.

“We found that the passive joint forces really do counterbalance the stronger of the flexor or extensor muscle in the animals and legs we looked at. In the horsehead grasshopper, for example, passive joint forces even differ between the middle legs (which are primarily used for walking) and the hind legs (which are adapted for jumping), even in the same individual animal. In both pairs of legs, the passive joint forces support the weaker muscle.

“This could be very important for the generation of movements in insects because the passive forces enable a transfer of energy from the stronger to the weaker muscle.”

This work helps to explain how insects control their movements using a close interplay of neuronal control and clever biomechanical tricks. Using balanced passive forces may provide engineers with new ways to improve the control of robotic and prosthetic limbs, say the researchers.

Dr Matheson concluded: “We hope that our work on locusts and grasshoppers will spur a new understanding of how limbs work and can be controlled, by not just insects, but by other animals, people, and even by robots.”

Filed under muscle movement motor control prosthetic limbs robotics neuroscience science

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Study Shows How Parkinson’s Disease Protein Acts like a Virus 
A protein known to be a key player in the development of Parkinson’s disease is able to enter and harm cells in the same way that viruses do, according to a Loyola University Chicago Stritch School of Medicine study.
The protein is called alpha-synuclein. The study shows how, once inside a neuron, alpha synuclein breaks out of lysosomes, the digestive compartments of the cell. This is similar to how a cold virus enters a cell during infection. The finding eventually could lead to the development of new therapies to delay the onset of Parkinson’s disease or halt or slow its progression, researchers said.
The study by virologist Edward Campbell, PhD, and colleagues, was published April 25, 2013 in the journal PLOS ONE.
Alpha-synuclein plays a role in the normal functioning of healthy neurons. But in Parkinson’s disease patients, the protein turns bad, aggregating into clumps that lead to the death of neurons in the area of the brain responsible for motor control. Previous studies have shown that these protein aggregates can enter and harm cells. Campbell and colleagues showed how alpha synuclein can bust out of lysosomes, small structures that collectively serve as the cell’s digestive system. The rupture of these bubble-like structures, known as vesicles, releases enzymes that are toxic to the rest of the cell.
“The release of lysosomal enzymes is sensed as a ‘danger signal’ by cells, since similar ruptures are often induced by invading bacteria or viruses,” said Chris Wiethoff, a collaborator on the study. “Lysosomes are often described as ‘suicide bags’ because when they are ruptured by viruses or bacteria, they induce oxidative stress that often leads to the death of the affected cell.”
In a viral or bacterial infection, the deaths of such infected cells may overall be a good thing for the infected individual. But in Parkinson’s disease, this same protective mechanism may lead to the death of neurons and enhance the spread of alpha-synuclein between cells in the brain, Campbell said. “This might explain the progressive nature of Parkinson’s disease. More affected cells leads to the spread of more toxic alpha-synuclein aggregates in the brain,” Campbell said. “This is very similar to what happens in a spreading viral infection.”
Campbell stressed that these studies need to be followed up and confirmed in other models of Parkinson’s disease. “Using cultured cells, we have made some exciting observations. However, we need to understand how lysosomal rupture is affecting disease progression in animal models of Parkinson’s disease and, ultimately, the brains of people affected by Parkinson’s disease. Can we interfere with the ability of alpha-synuclein to rupture lysosomes in these settings? And will that have a positive effect on disease progression? These are the questions we are excited to be asking next.”
Jeffrey H. Kordower, PhD, professor of neurological sciences, professor of neurosurgery and director of the Research Center for Brain Repair at Rush University Medical Center, said the study “is an important finding by a group of investigators who are beginning to make their impact in the field of Parkinson’s disease. This paper adds to the growing concept that alpha-synuclein, a  main culprit in the cause of Parkinson’s disease, can transfer from cell to cell. This paper elegantly puts a mechanism behind such a transfer. The findings will help shape the direction of Parkinson’s disease research for years to come.”

Study Shows How Parkinson’s Disease Protein Acts like a Virus

A protein known to be a key player in the development of Parkinson’s disease is able to enter and harm cells in the same way that viruses do, according to a Loyola University Chicago Stritch School of Medicine study.

The protein is called alpha-synuclein. The study shows how, once inside a neuron, alpha synuclein breaks out of lysosomes, the digestive compartments of the cell. This is similar to how a cold virus enters a cell during infection. The finding eventually could lead to the development of new therapies to delay the onset of Parkinson’s disease or halt or slow its progression, researchers said.

The study by virologist Edward Campbell, PhD, and colleagues, was published April 25, 2013 in the journal PLOS ONE.

Alpha-synuclein plays a role in the normal functioning of healthy neurons. But in Parkinson’s disease patients, the protein turns bad, aggregating into clumps that lead to the death of neurons in the area of the brain responsible for motor control. Previous studies have shown that these protein aggregates can enter and harm cells. Campbell and colleagues showed how alpha synuclein can bust out of lysosomes, small structures that collectively serve as the cell’s digestive system. The rupture of these bubble-like structures, known as vesicles, releases enzymes that are toxic to the rest of the cell.

“The release of lysosomal enzymes is sensed as a ‘danger signal’ by cells, since similar ruptures are often induced by invading bacteria or viruses,” said Chris Wiethoff, a collaborator on the study. “Lysosomes are often described as ‘suicide bags’ because when they are ruptured by viruses or bacteria, they induce oxidative stress that often leads to the death of the affected cell.”

In a viral or bacterial infection, the deaths of such infected cells may overall be a good thing for the infected individual. But in Parkinson’s disease, this same protective mechanism may lead to the death of neurons and enhance the spread of alpha-synuclein between cells in the brain, Campbell said. “This might explain the progressive nature of Parkinson’s disease. More affected cells leads to the spread of more toxic alpha-synuclein aggregates in the brain,” Campbell said. “This is very similar to what happens in a spreading viral infection.”

Campbell stressed that these studies need to be followed up and confirmed in other models of Parkinson’s disease. “Using cultured cells, we have made some exciting observations. However, we need to understand how lysosomal rupture is affecting disease progression in animal models of Parkinson’s disease and, ultimately, the brains of people affected by Parkinson’s disease. Can we interfere with the ability of alpha-synuclein to rupture lysosomes in these settings? And will that have a positive effect on disease progression? These are the questions we are excited to be asking next.”

Jeffrey H. Kordower, PhD, professor of neurological sciences, professor of neurosurgery and director of the Research Center for Brain Repair at Rush University Medical Center, said the study “is an important finding by a group of investigators who are beginning to make their impact in the field of Parkinson’s disease. This paper adds to the growing concept that alpha-synuclein, a  main culprit in the cause of Parkinson’s disease, can transfer from cell to cell. This paper elegantly puts a mechanism behind such a transfer. The findings will help shape the direction of Parkinson’s disease research for years to come.”

Filed under parkinson's disease alpha-synuclein proteins motor control lysosomes neuroscience science

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New model of how brain functions are organized may revolutionize stroke rehab
A new model of brain lateralization for movement could dramatically improve the future of rehabilitation for stroke patients, according to Penn State researcher Robert Sainburg, who proposed and confirmed the model through novel virtual reality and brain lesion experiments.
Since the 1860s, neuroscientists have known that the human brain is organized into two hemispheres, each of which is responsible for different functions. Known as neural lateralization, this functional division has significant implications for the control of movement and is familiar in the phenomenon of handedness.
Understanding the connections between neural lateralization and motor control is crucial to many applications, including the rehabilitation of stroke patients. While most people intuitively understand handedness, the neural foundations underlying motor asymmetry have until recently remained elusive, according to Sainburg, professor of kinesiology and neurology and participant in the neuroscience and physiology graduate programs at the University’s Huck Institutes of the Life Sciences.
Research by Sainburg and his colleagues in the Center for Motor Control and published in the journal Brain has revealed a new model of motor lateralization that accounts for the neural foundations of handedness. The discovery could fundamentally change the way post-stroke rehabilitation is designed.
"Each hemisphere of the brain is specialized for different aspects of motor control, and thus each arm is ‘dominant’ for different features of movement," said Sainburg. "The dominant arm is used for applying specific force sequences — such as when slicing a loaf of bread with a knife — and the other arm is used for impeding forces to maintain stable posture, such as holding the loaf of bread. Together these specialized control mechanisms are seamlessly integrated into every day activities.
"Our research has shown that this integration breaks down in neural disorders such as stroke, which produces different motor deficits depending on whether the right or left hemisphere has been damaged," Sainburg continued. "Traditionally, physical rehabilitation professionals have used the same protocols to practice movements of the paretic arm, regardless of the hemisphere that has been damaged. Our research shows that each arm should be treated for different control deficits, and it also indicates that therapists should directly retrain patients in how to use the two arms together in order to recover function."
In preparing to test their model, Sainburg and his team selected study participants from the New Mexico Veterans Administration Hospital and Penn State Milton S. Hershey Medical Center based on specific criteria in order to accurately distinguish the motor control mechanisms specific to each brain hemisphere. Participants were then asked to perform a series of tasks on a virtual reality interface, programmed and designed by Sainburg, which allowed the researchers to record detailed 3D position and motion data. The data for all the participants’ hand trajectories and final positions were then aggregated to compare the effects of left versus right hemisphere damage on different aspects of control.
"Our results indicated that while both groups of patients showed similar clinical impairment in the contralesional arm, this was produced by different motor control deficits," Sainburg said. "Right hemisphere damaged patients were able to make straight movements that were directed toward the targets, but were unable to stabilize their arms in the targets at the end of motion. In contrast, left hemisphere damaged patients were unable to make straight and efficient movements, but had no difficulty stabilizing their arms at the end of motion. These results confirmed that each hemisphere contributes unique control to its contralesional arm, verifying why our arms seem different when we use them for the same tasks."
Results mirror those of Sainburg’s prior studies of motor deficits in unilateral stroke patients, focused on the ipsilesional arm, which formed the basis for his model of lateralization.
"Because both arms in stroke patients show motor deficits that are specific to the hemisphere that was damaged, we have concluded that the left arm is not simply controlled with the right hemisphere and vice versa," Sainburg said. "This is a revolutionarily new perspective on sensorimotor control: each hemisphere contributes different control mechanisms to the coordination of both arms, regardless of which arm is considered dominant."
Sainburg and his colleagues are currently designing follow-up studies that will aid the development of new rehabilitation protocols addressing the specific motor deficits associated with each hemisphere.

New model of how brain functions are organized may revolutionize stroke rehab

A new model of brain lateralization for movement could dramatically improve the future of rehabilitation for stroke patients, according to Penn State researcher Robert Sainburg, who proposed and confirmed the model through novel virtual reality and brain lesion experiments.

Since the 1860s, neuroscientists have known that the human brain is organized into two hemispheres, each of which is responsible for different functions. Known as neural lateralization, this functional division has significant implications for the control of movement and is familiar in the phenomenon of handedness.

Understanding the connections between neural lateralization and motor control is crucial to many applications, including the rehabilitation of stroke patients. While most people intuitively understand handedness, the neural foundations underlying motor asymmetry have until recently remained elusive, according to Sainburg, professor of kinesiology and neurology and participant in the neuroscience and physiology graduate programs at the University’s Huck Institutes of the Life Sciences.

Research by Sainburg and his colleagues in the Center for Motor Control and published in the journal Brain has revealed a new model of motor lateralization that accounts for the neural foundations of handedness. The discovery could fundamentally change the way post-stroke rehabilitation is designed.

"Each hemisphere of the brain is specialized for different aspects of motor control, and thus each arm is ‘dominant’ for different features of movement," said Sainburg. "The dominant arm is used for applying specific force sequences — such as when slicing a loaf of bread with a knife — and the other arm is used for impeding forces to maintain stable posture, such as holding the loaf of bread. Together these specialized control mechanisms are seamlessly integrated into every day activities.

"Our research has shown that this integration breaks down in neural disorders such as stroke, which produces different motor deficits depending on whether the right or left hemisphere has been damaged," Sainburg continued. "Traditionally, physical rehabilitation professionals have used the same protocols to practice movements of the paretic arm, regardless of the hemisphere that has been damaged. Our research shows that each arm should be treated for different control deficits, and it also indicates that therapists should directly retrain patients in how to use the two arms together in order to recover function."

In preparing to test their model, Sainburg and his team selected study participants from the New Mexico Veterans Administration Hospital and Penn State Milton S. Hershey Medical Center based on specific criteria in order to accurately distinguish the motor control mechanisms specific to each brain hemisphere. Participants were then asked to perform a series of tasks on a virtual reality interface, programmed and designed by Sainburg, which allowed the researchers to record detailed 3D position and motion data. The data for all the participants’ hand trajectories and final positions were then aggregated to compare the effects of left versus right hemisphere damage on different aspects of control.

"Our results indicated that while both groups of patients showed similar clinical impairment in the contralesional arm, this was produced by different motor control deficits," Sainburg said. "Right hemisphere damaged patients were able to make straight movements that were directed toward the targets, but were unable to stabilize their arms in the targets at the end of motion. In contrast, left hemisphere damaged patients were unable to make straight and efficient movements, but had no difficulty stabilizing their arms at the end of motion. These results confirmed that each hemisphere contributes unique control to its contralesional arm, verifying why our arms seem different when we use them for the same tasks."

Results mirror those of Sainburg’s prior studies of motor deficits in unilateral stroke patients, focused on the ipsilesional arm, which formed the basis for his model of lateralization.

"Because both arms in stroke patients show motor deficits that are specific to the hemisphere that was damaged, we have concluded that the left arm is not simply controlled with the right hemisphere and vice versa," Sainburg said. "This is a revolutionarily new perspective on sensorimotor control: each hemisphere contributes different control mechanisms to the coordination of both arms, regardless of which arm is considered dominant."

Sainburg and his colleagues are currently designing follow-up studies that will aid the development of new rehabilitation protocols addressing the specific motor deficits associated with each hemisphere.

Filed under stroke rehabilitation rehabilitation brain lateralization motor control handedness hemispheres neuroscience science

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Motor skills research nets good news for middle-aged

People in their 20s don’t have much on their middle-aged counterparts when it comes to some fine motor movements, researchers from UT Arlington have found.

In a simple finger-tapping exercise, study participants’ speed declined only slightly with age until a marked drop in ability with participants in their mid-60s.

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Priscila Caçola, an assistant professor of kinesiology at The University of Texas at Arlington, hopes the new work will help clinicians identify abnormal loss of function in their patients. Though motor ability in older adults has been studied widely, not a lot of research has focused on when deficits begin, she said.

The journal Brain and Cognition will include the study in its June 2013 issue. It is already available online.

“We have this so-called age decline, everybody knows that. I wanted to see if that was a gradual process,” Caçola said. “It’s good news really because I didn’t see differences between the young and middle-aged people.”

Caçola’s co-authors on the paper are Jerroed Roberson, a senior kinesiology major at UT Arlington, and Carl Gabbard, a professor in the Texas A&M University Department of Health and Kinesiology.

The researchers based their work on the idea that before movements are made, the brain makes a mental plan. They used an evaluation process called chronometry that compares the time of test participants’ imagined movements to actual movements. Study participants – 99 people ranging in age from 18 to 93 – were asked to imagine and perform a series of increasingly difficult, ordered finger movements. They were divided into three age groups – 18-32, 40-63 and 65-93 – and the results were analyzed.

“What we found is that there is a significant drop-off after the age of 64,” Roberson said. “So if you see a drop-off in ability before that, then it could be a signal that there might be something wrong with that person and they might need further evaluation.”

The researchers also noted that the speed of imagined movements and executed actions tended to be closely associated within each group. That also could be useful knowledge for clinicians, the study said.

“The important message here is that clinicians should be aware that healthy older adults are slower than younger adults, but are able to create relatively accurate internal models for action,” the study said.

Caçola is a member of UT Arlington Center for Health Living and Longevity. She has published previous research on the links between movement representation and motor ability in children.

Filed under aging motor skills motor control brain psychology neuroscience science

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Theresa Klein talks about Achilles, the first machine to move in a biologically accurate way.  
"Our robot, named Achilles, is the first to walk in a biologically accurate way. That means it doesn’t just move like a person, but also sends commands to the legs like the human nervous system does.
Each leg has eight muscles—Kevlar straps attached to a motor on one end and to the plastic skeleton on the other. As the motor turns, it pulls the strap, mimicking the way our muscles contract. Some of Achilles’ muscles extend from the hip or thigh to the lower leg so they can project forces all the way down the limb. This allows us to put most of the motors in the hips and thighs. Placing them up high keeps the lower leg light, so that it can swing quickly like a human’s lower leg.
In people, neurons in the spinal column send out rhythmic signals that control our legs. It’s like a metronome, and sensory feedback from the legs alters the pace. Your brain can step in to make corrections, but it doesn’t explicitly control every muscle, which is essentially why you can walk without thinking about it. For our robot, a computer program running off an external PC controls movement in a similar way. With each step, the computer sends a signal to flex one hip muscle and extend the other. The computer changes the timing of those signals based on feedback from the legs’ load and angle sensors. A similar control system handles the lower muscles.
Modeling human movement has applications outside of robotics. It could also help us understand how people recover after spinal-cord injuries, for example. But our robot is still a very simplified model—it has no torso and can’t handle complex terrain. Initially, we also had a problem with its feet slipping. We thought about different types of rubber to give its feet more grip but eventually realized a solution already exists. Now, the robot wears a pair of Keds.”

Theresa Klein talks about Achilles, the first machine to move in a biologically accurate way.

"Our robot, named Achilles, is the first to walk in a biologically accurate way. That means it doesn’t just move like a person, but also sends commands to the legs like the human nervous system does.

Each leg has eight muscles—Kevlar straps attached to a motor on one end and to the plastic skeleton on the other. As the motor turns, it pulls the strap, mimicking the way our muscles contract. Some of Achilles’ muscles extend from the hip or thigh to the lower leg so they can project forces all the way down the limb. This allows us to put most of the motors in the hips and thighs. Placing them up high keeps the lower leg light, so that it can swing quickly like a human’s lower leg.

In people, neurons in the spinal column send out rhythmic signals that control our legs. It’s like a metronome, and sensory feedback from the legs alters the pace. Your brain can step in to make corrections, but it doesn’t explicitly control every muscle, which is essentially why you can walk without thinking about it. For our robot, a computer program running off an external PC controls movement in a similar way. With each step, the computer sends a signal to flex one hip muscle and extend the other. The computer changes the timing of those signals based on feedback from the legs’ load and angle sensors. A similar control system handles the lower muscles.

Modeling human movement has applications outside of robotics. It could also help us understand how people recover after spinal-cord injuries, for example. But our robot is still a very simplified model—it has no torso and can’t handle complex terrain. Initially, we also had a problem with its feet slipping. We thought about different types of rubber to give its feet more grip but eventually realized a solution already exists. Now, the robot wears a pair of Keds.”

Filed under Achilles mimicking motor control muscles neuroscience robotics robots science technology

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