Tag Archives: Nerves

Old and young.

Time flies as we age because our brains get bigger and less efficient, a new paper proposes

New research from Duke University says time flies as we age because of our brains maturing — and degrading.

Old and young.

Image credits Gerd Altmann.

The shift in how we perceive time throughout our lives takes place because our brain’s ability to process images slows down, reports a study penned by Adrian Bejan, the J.A. Jones Professor of Mechanical Engineering at Duke. This is a consequence of the natural development of our brains, as well as wear and tear.

Hardware, oldware

“People are often amazed at how much they remember from days that seemed to last forever in their youth,” said Bejan. “It’s not that their experiences were much deeper or more meaningful, it’s just that they were being processed in rapid fire.”

Bejan says that, as the bundles of nerves and neurons that make up our brains develop both in size and complexity, the electrical signals that encode sensory data have to travel through longer paths. We also grow in size, making the nerves feeding information to the brain physically longer. Nerve fibers are good conductors of electricity — but they’re not perfect; all that extra white matter slows down the transfer of data in our biological computers.

Wear and tear also play a role, he adds. As neural paths age, they also degrade, which further chips away at their ability to transport information.

These two elements combine to slow down our brain’s ability to transport, and thus process, data. One tell-tale sign of processing speeds degrading with age is the fact that infants tend to move their eyes more often than adults, Bejan explains. It’s not that they’re more ‘filled with energy’ or simply have shorter attention spans. Younger brains are quicker to absorb, process, and integrate new information, meaning they need to focus for shorter spans of time on a single object or stimuli to take it all in.

So, how does this impact our perception of time? The study explains that older people basically view fewer new images in a given unit of time than younglings, due to the processes outlined above. This makes it feel like time is passing more quickly for the former.  Objective, “measurable ‘clock time’ is not the same as the time perceived by the human mind,” the paper reads, as our brains tend to keep track of time by how many new bits of information it receives.

“The human mind senses time changing when the perceived images change,” said Bejan. “The present is different from the past because the mental viewing has changed, not because somebody’s clock rings.”

“Days seemed to last longer in your youth because the young mind receives more images during one day than the same mind in old age.”

It’s not the most heartening of results — who likes to hear their brains are getting laggy, right? — but it does help explain why we get that nagging feeling of time moving faster as we age. And, now that we know what’s causing it, we can try to counteract the effects.

That being said, maybe having a slower brain isn’t always that bad of a thing. If you’re stuck out on a boring date, or grinding away inside a cubicle from 9 to 5, at least you feel like you’re getting out quicker. Glass half full and all that, I suppose.

The paper “Why the Days Seem Shorter as We Get Older” has been published in the journal European Review.

The nervous system is like an electrical wiring. Credit: GuidesHealth.com

Scientists coax mice with injured spinal cords to regrow nerve fibers, something deemed impossible not too long ago

The nervous system is like an electrical wiring. Credit: GuidesHealth.com

The nervous system is like electrical wiring for your body. Credit: GuidesHealth.com

German researchers proved that nerve cells can regenerate in mice who suffered spinal cord injuries. These sort of injuries cause permanent disabilities like paralysis because the nerves do not regenerate by themselves. Though thought impossible, the researchers showed that they could coax one of the rodents’ molecular mechanisms to start producing new nerve cells in the site of injury using a drug called Pregabalin.

Helping neurons reach out their arms again

The human nervous system is comprised of an intricate network of nerve cells that transmit signals between different parts of the body, from head to toe. It helps to imagine this network like the body’s electrical wiring, which starts at the brain then branches out throughout the entire body. Damages to this wiring system can be catastrophic — an injury to the spinal cord, for instance, might cut the sensory input from the damaged site down. That’s because, again like an electrical wire, the neurons of the central nervous systems are connected by long projections called axons. When the axons are severed, these are unable to regrow leaving the connection discontinued permanently.

Scientists know that these axons grow during the embryonic development stage. They stop extending their arms past this stage, though. But if there’s a molecular mechanism that instructs the neuron’s axons to grow and to stop later at some point, then there’s a chance we can re-activate this re-growth process by targetting its underlying molecular brake.

This is what researchers at the German Center for Neurodegenerative Diseases (DZNE) set out to do. They quickly realized it was like looking for a needle in a haystack. That’s because there are literally hundreds of active genes in every nerve cell, says neurobiologist Frank Bradke who is one the lead authors of the study.

If it weren’t for computers and algorithms that can comb through vast databases, Bradke and colleagues might have still been at it. Thanks to bioinformatics, though, they managed to zero in on a promising candidate — a gene called Cacna2d2, which is known to play an important role in synapse formation and function.

Cacna2d2 has the blueprint for the production of a protein that anchors ion channels in the cell membrane. This mechanism regulates the flow of calcium ions into the nerve cell which is integral to the release of neurotransmitters, be them serotonin or dopamine.

Investigating further, Bradke and colleagues found that a drug called Pregabalin (PGB) can bind to these calcium channel molecular anchors. They gave PGB to mice who had undergone spinal cord trauma and later found this treatment spurred new nerve connections to grow, as reported in the journal Neuron.

“Our study shows that synapse formation acts as a powerful switch that restrains axonal growth. A clinically-relevant drug can manipulate this effect,” says Bradke.

Hopefully, the first human trials with PGB might start soon, considering the drug is already prescribed to spinal cord injured patients. PGB is prescribed for its pain relieving properties and often late, a long time after the injury occurred. Until then, there are other intriguing developments. Previously, another group from Germany grew spinal cords in a petri dish and, elsewhere in Switzerland, researchers used a flexible ribbon-like implant that attaches itself to a paralyzed rat’s spinal cord allowing the rodent to walk again.

“PGB might have a regenerative effect in patients, if it is given soon enough. In the long term this could lead to a new treatment approach. However, we don’t know yet,” Bradke added.

We’ll soon be able to hack our nerves into controlling diseases

A novel treatment method, which involves applying an electrical current to nerve cells, could help treat a wide range of conditions, from diabetes to arthritis, according to medical company Galvani Bioelectronics. With backing from GSK and Verily Life Sciences, Galvani hopes to bring their technique within seven years.

“Neuron” sculpture by Roxy Paine.
Image credits Christopher Neugebauer / Flickr.

During animal trials, Galvani researchers attached electrodes housed in tiny silicone cuffs around nerves and used to control the messages it carries. During one set of tests, the results suggested that the method could be used to treat type-2 diabetes, a metabolic disorder in which the body becomes resistant to insulin and produces too little of the hormone.

The team focused on a cluster of nerves in the animals’ necks near the main artery, which serve to check sugar an insulin hormone levels in the blood. They feed information to the brain, which in turn sends instructions to raise or lower these concentrations.

“The neural signatures in the nerve increase in type 2-diabetes,” said GSK vice-president of bioelectronics Kris Famm for BBC News. “By blocking those neural signals in diabetic rats, you see the sensitivity of the body to insulin is restored.”

And the applications don’t stop there.

“It isn’t just a one-trick-pony, it is something that if we get it right could have a new class of therapies on our hands,” Mr Famm said.

He also added that we’ve only begun “scratching the surface” when it comes to understanding how each nerve signal affects our body. We don’t even know if it’s just an issue of turning a nerve on or off, or if the signal’s volume and rhythm make a difference. And even if the approach works theoretically, a huge amount of effort will be needed to make the technology practical. So don’t expect your doctor to suggest it anytime too soon.

But once it becomes available, the electrode kits will be miniaturized and customizable to different pairs of nerves, durable enough to survive in your body for extended periods of time, and powered by efficient batteries — so kind of like pacemakers, but for nerves. So when will they become available?

“In 10 to 20 years I think there will be a set of these miniaturised precision therapies that will be available for you and me when we go to a doctor,” Dr Famm said.

“Bioelectronic medicine is a new area of therapeutic exploration, and we know that success will require the confluence of deep disease biology expertise and new highly miniaturised technologies,” added Verily chief technology officer Brian Otis.

“This partnership provides an opportunity to further Verily’s mission by deploying our focused expertise in low power, miniaturised therapeutics and our data analytics engine to potentially address many disease areas with greater precision with the goal of improving outcomes.”

Researchers coax neurons into regenerating and restore vision in mice

Stanford University researchers have developed a method that allows them to regrow and form connections between neurons involved in vision. The method has been only tested on mice but the results suggest that mammalian brain cells can be restored after being damaged — meaning maladies including glaucoma, Alzheimer’s disease, and spinal cord injuries might be more repairable than has long been believed.

Neurons are the building blocks of our nervous system.
Image via youtube

It has long been believed that mammalian brain cells can’t regrow, but the new study shows that it’s possible. The team reports that they’ve managed to regenerate the axons of retinal ganglion cells, and although fewer than 5 percent of cells responded to the method, it was enough to make a difference in the mice’s vision.

“The brain is very good at coping with deprived inputs,” says Andrew Huberman, the Stanford neurobiologist who led the work. “The study also supports the idea that we may not need to regenerate every neuron in a system to get meaningful recovery.”

“I think it’s a significant step forward toward getting to the point where we really can regenerate optic nerves,” says Johns Hopkins professor of ophthalmology Don Zack, who was not involved in the research. “[It is] one more indication that it may be possible to bring that ability back in humans.”

The study shows that a regenerating axon can grow in the right direction, forming the connections needed to restore function.

“They can essentially remember their developmental history and find their way home,” Huberman says. “This has been the next major milestone in the field of neural regeneration.”

Once central nervous system cells reach maturity, they flip a genetic switch and never grow again. The team used genetic manipulation to flip this switch back on, activating the so-called “mammalian target of rapamycin” (mTOR) signaling pathway, which helps stimulate growth. At the same time, they exercised the damaged eye by showing mice a display of moving, high-contrast stripes.

“When we combined those two [methods]—molecular chicanery with electrical activity—we saw this incredible synergistic effect,” Huberman says. “The neurons grew enormous distances—500 times longer and faster than they would ordinarily.”

They observed that by covering the mice’s good eyes so they looked at the stripes only with their damaged eyes, the neurons regenerated faster. The team used a virus to deliver the altered genes to their mice, but study co-author Zhigang He believes there may be simpler ways to achieve this, such as pills, for human treatment. He, who developed the mTOR procedure, isn’t sure how the findings will impact human patients. He notes that a dual procedure, similar to that they used for the rats, hasn’t yet been developed for humans. He also pointed out that our retinal cells would have to grow a lot more than a mouse’s to rewire vision.

“The human optic nerve has to regenerate not on the scale of millimeters but on the scale of centimeters,” he explains.

Further research is needed to figure out the best use of this method for patients.

“Before, there was nothing to do” about damage to retinal nerves or other brain cells, says He, whose lab studies both retinal and spinal cord damage. “Now, we need to think about what type of patient might be most likely to benefit from the treatment.”

Huberman hopes that his method will be usable within a few years to help patients with early-stage glaucoma avoid the degeneration that leads to blindness.

“There are going to be many, many cases in which glaucoma could be potentially treated by enhancing the neural activity of retinal ganglion cells,” he says.

The findings also suggest that other brain cells could be determined to self-repair, Huberman says. Potential applications include restoring some movement after spinal cord damage, fighting memory-related diseases such as Alzheimer’s and even helping patients manage the symptoms of autism.

The full paper, titled “Neural activity promotes long-distance, target-specific regeneration of adult retinal axons” has been published in the journal Nature Neuroscience.

For the first time in history, researchers restore voluntary finger movement for a paralyzed man

Using two sets of electrodes, scientists have successfully restored finger movement in a paralyzed patient for the first time in history. The results could be the starting point to developing methods that would allow people around the planet to regain limb mobility.

Four years ago, Ian Burkhart lost the ability to move his arms and legs. Now thanks to a neural implant and electrodes on his forearm, he's able to move his wrist, hand, and fingers. Image credits Ohio State University Wexner Medical Center/ Batelle

Four years ago, Ian Burkhart lost the ability to move his arms and legs. Now thanks to a neural implant and electrodes on his forearm, he’s able to move his wrist, hand, and fingers.
Image credits Ohio State University Wexner Medical Center/ Batelle

There are roughly 250,000 people living with severe spinal cord injuries in America alone — people who have to manage going through life with little or no mobility. One such man is 24 year old Ian Burkhart, who lost the ability to move or feel from the shoulder down in a diving accident four years ago. But, thanks to a team at Ohio State University, Ian became the first to regain control over his body. By using electrodes to bypass his damaged nerve pathways, the researchers allowed him to move his right fingers, hand and wrist.

“My immediate response was I want to do this,” said Ian after the four-hour procedure of inserting the electrodes into his brain . “If someone else was in my place, with the possibility of changing my life and people like me in future, I would hope they would agree.”

The first step was to implant an array of electrodes into Burkhart’s left primary motor cortex, an area of the brain that handles planing and directing movements. Signals generated in his brain were recorded and fed through a machine learning algorithm. It took almost 15 months of three training sessions each week to teach his brain to use the device. But finally, the software started to correctly interpret which brain waves corresponded to which movements.

Now, when Burkhart’s brain emits the proper signals, the implant sends these impulses through wires to a flexible sleeve — lined with electrodes — placed around his wrists to stimulate his muscles accordingly.

Image via giphy

The researchers tested Burkhart’s ability to perform six different hand, wrist and finger movements. An algorithm determined that Burkhart’s first movements were about 90 percent accurate on average.After his muscles got some exercise and improved their strength, Ian successfully poured water from a bottle into a jar and then stirred it. He was also able to swipe a credit card and even play some Guitar Hero.

The team notes that in its current form, the technique is highly invasive, meaning it might not be suitable for patients who are already in poor health or have compromised immune systems; They also point out that the device they used in this study allows for a greater range of movement than typically available neural bypass devices. Finally, the implant doesn’t restore a patient’s ability to feel — prosthetics might be able to solve that problem though.. Maybe someday the two technologies could merge to give patients both the ability to move and to feel.

Still, the study is a huge stepping stone. The way Burkhart was able to move his hand is simply mind blowing, and something considered impossible up to now. That could have big implications if the technology becomes used widely.

“Our goal was to use this technology so that these patients like Ian can be more in charge of their lives and can be more independent,” Ali Rezai, one of the researchers involved in the study, said in a statement. “This really provides hope, we believe, for many patients in the future.”

The team hopes to have their system refined and ready for wide-scale implementation in a few years.

The full paper, titled “Restoring cortical control of functional movement in a human with quadriplegia” has been published in the journal Nature and can be read here.

Artificial skin can feel pressure, then tell your brain about it

Prosthetics has come a long way from its humble beginnings – the crude wooden legs of yore are a far cry from the technological marvels we can create to replace our limbs today. However, there is one thing that, with all our know-how, we haven’t yet been able to incorporate in them: a sense of touch. A research team from Stanford University aims to fix this shortcoming, and has developed technology that can “feel” when force is exerted upon it, then transmit the sensory data to neurons – in essence, they’ve created an artificial skin.

Image via factor-tech

Image via factor-tech

Tactile sense is a very important source of information for our brains, and having an otherwise functioning limb that doesn’t feel what it’s touching is something most of us can’t even imagine. Sit on your hand till it goes numb, then try to tie your laces – it’s frustratingly hard, and personally, I find the sensation disturbing.

Now imagine that numbness persists for your whole life. That’s what prosthetic users have to live with, a serious limitation imposed on even the most effective prosthetic. Without tactile sensitivity, it’s hard to maintain optimal motor control, and it’s impossible to know how much force you’re exerting on an object, or it’s temperature and texture, for example. To make matters worse, having a sense of touch (even the illusion of it) is one of the best ways to alleviate phantom limb pain, which affects nearly 80% of amputees.

The human skin is a superbly complex and well tuned sensory organ – so much so in fact, that we may never be capable of creating something that reacts to stimulus in quite the same way it does. But the Stanford team, led by electrical engineer Benjamin Tee, recently performed a proof-of-concept experiment that brought artificial tactile sense from the realm of sci-fi one step closer to reality. They used flexible organic circuits and innovative pressure sensors to create a skin-like interface that can sense the force of static objects. Data recorded by the device was transmitted via optogenetic to cultured mice brain cells. Their work was published in the journal Science.

The DiTact

Artificial mechanoreceptors mounted on the fingers of a model robotic hand.
Image via phys

The system, dubbed “DiTact” (Digital Tactile System) relies on low-power, flexible organic transistor circuitry, that can translate pressure into the same signals our natural mechanoreceptors generate. To make the sensors precise and to give them a wide enough range of pressure recording, the team created them out of carbon nanotubes shaped into tiny pyramidal structures.

“Our sensor was made of tiny pyramids of rubber with carbon nanotubes distributed in it,” noted study co-author Alex Chortos. “This structure was very useful because it allowed us to easily change a few things, like the distance between the pyramids, the size of the pyramids, and the concentration of carbon nanotubes in order to get the ideal pressure sensing characteristics in the right range.”

The nanostructure of the pyramids allowed the researchers to increase the sensors’ precision close to the levels of our own cutaneous receptors.

Interfacing

But just having sensors isn’t enough, all the magic happens in the brain. To create sensation, the researchers took the signals from the piezometers and transferred them via optic cables to mouse cortical neurons – as the technology is still in an early stage of development, the cells were cultured in vitro rather than use the brains of live animals.

But using the same technique, signals from a prosthesis coated with DiTact could be fed directly to the brain of a living human – optogenetics has been successfully used on live subjects before. All that is needed is for a number of neurons to be genetically altered to respond to light signals. Using a transgene obtained from certain algae strands, neurons can be made to fire electrical signals when exposed to blue light, or to yellow light using a bacterial transgene.

However, because of the rate at which sensory information is processed by neurons, the team had to implement a few of their own changes to the classical method.

“Biological mechanoreceptors are able to produce signals as fast as several hundred electrical pulses per second,” says Chortos. “Previous optogenetic technologies were only capable of stimulating brain cells much slower than we need to mimic real mechanoreceptors.”

Luckily, Chortos knew of the work of Andre Berndt and Karl Deisseroth who developed a new type of optogenetic treatment that allows brain cells to be stimulated very rapidly so that they’re compatible with the speed of real mechanoreceptors. Using the new optogenetic proteins, the neurons were able to sustain longer intervals of stimulation, suggesting that the system could also work with other fast-firing neurons, including peripheral nerves. This, the team says, means that DiTact will likely work with live mice or humans, and the good results they’ve seen up to know means that they will test the system on a live mouse as soon as possible.

Getting a feel for the future

“We could validate that our sensor is conveying the correct information to [a live] animal by using behavioral cues, i.e. how the animal behaves in response to pressure,” said Chortos. “The ultimate test will be to attach the sensor to a human and ask them what they feel. In order to get truly natural touch sensing, we may need to modify and tweak our design.”

“We envision our artificial mechanoreceptors making the greatest impact via integration for sensory feedback with prosthetic systems in development by other groups,” noted co-author Amanda Nguyen. “As our sensor would be mounted alongside artificial limb systems, the primary safety concerns are centered around nerve stimulation patterns and interface.”

Nguyen notes that while the early work on sensory feedback with neurally interfaced prosthetics shows great promise, we need to truly understand how to effectively and safely stimulate nerves in order to provide realistic sensory feedback.

“As a greater understanding of stimulation parameters is gained, the output of our artificial mechanoreceptor will be tuned to follow these stimulation paradigms,” she said. “With demonstrated efficacy and safety, the potential for improving the quality of life for individuals with tactile impairments can be balanced with the ethical concerns raised by neuroprosthetics. Accessibility of this type of technology in humans will grow as both our understanding of neuroscience grows and prosthetic technology advances to provide nuanced sensory perceptions.”