Posts Tagged ‘ therapy ’

Guiding Neuron Growth

Our neurons’ growth can be shaped by tiny cues from spinning microparticles in the fluids that surround them, a new study reports.

An axon gets all friendly with a spinnin' microparticle.

The branching and growth of neurons is based on several kinds of guides, including their chemical environment, their location within the brain, and the dense network of glial cells that support and protect them. But as it turns out, they’re also surprisingly responsive to fluid dynamics, turning in response to the rotation of nearby microparticles – a bit like the way a vine can climb a fence-post.

Since the early days of neuroscience, researchers have dreamed of growing and shaping neurons for specific purposes – to patch gaps in damaged neural networks, for example; or just to test their workings under controlled lab conditions.

But it’s only in the past few years that technologies like microfluidic chambers and pluripotent stem cells have enabled researchers to grow healthy, living neurons according to precise specifications, and study those cells’ responses to all kinds of stimuli. In fact, it looks like it won’t be much longer ’til doctors can implant networks of artificially grown neurons directly into living adult brains.

But as the journal Nature Photonics reports, the big breakthrough this time comes from Samarendra Mohanty at The University of Texas at Arlington, who found that neuron growth can respond to physical cues – spinning particles in fluid, for instance – as well as to chemical ones.

Mohanty’s team discovered this by using a tiny laser to direct the spin of a microparticle positioned next to the axon of a growing neuron. The spinning particle generated a miniature counterclockwise vortex in the fluid – and wouldn’t ya know it; the axon started wrapping around the spinning particle as the neuron grew:

Circularly polarized light with angular momentum causes the trapped bead to spin. This creates a localized microfluidic flow … against the growth cone that turns in response to the shear.

In short, this is the first time a scientific team has used a mechanical device – a “micro-motor,” as they call it – to directly control and precisely adjust the growth of a single axon:

The direction of axonal growth can be precisely manipulated by changing the rotation direction and position of this optically driven micromotor.

So far, the micromotor only works 42 percent of the time – but the team is optimistic that future tests will lead to greater reliability and more precise control. In the near future, micromotors like this one could be used to turn the growth of an axon back and forth – or even to funnel growth through “gauntlets” of spinning particles.

Most conveniently of all, the particles could be injected, re-positioned, and removed as needed – providing a much simpler, more modifiable architecture than any other neuron-shaping technology in use today.

And for the slightly more distant future, Mohanty’s lab is hard at work on a system for providing long-range, long-term guidance to entire neural networks through completely non-invasive optical methods.

Until then, though, isn’t it amazing to stop and think about all the neurons that are growing and reshaping themselves – all the delicate intertwining lattices relaying millions of mysterious coded messages, right now, within the lightless interior of your own head?

Call me self-centered, but I think it’s just about the coolest thing on planet Earth.

Wakefulness Cells

Certain groups of neurons determine whether light keeps us awake or not, says a new study.

Just a typical day for a hypocretin-deficient mouse. Okay, I'll wait for you to finish making that squinchy "Awww!" face, and then we'll move on with the article.

In the hypothalamus – a brain structure responsible for regulating hormone levels – specific kinds of neurons release a hormone called hypocretin (also known as hcrt or orexin). Hypocretin lets light-sensitive cells in other parts of the brain – such as the visual pathway – know that they should respond to incoming light by passing along signals for us to stay awake.

Scientists have understood for centuries that most animals and plants go through regular cycles of wakefulness and sleep – they call these patterns circadian rhythms or circadian cycles. More recently, researchers have begun unraveling the various chemical messaging systems our bodies use to time and control these cycles – enzymes like PER and JARID1a, which help give us an intuitive sense of how long we’ve been awake or asleep.

But now, as the Journal of Neuroscience reports, a team led by UCLA’s Jerome Siegel has isolated a neurochemical messaging system that dictates whether or not we can stay awake during the day at all. The team bred a special strain of mice whose brains were unable to produce hypocretin, and found that these mice acted like students in first-period algebra – even under bright lights, they just kept dozing off. However, they did jump awake when they received a mild electric shock:

This is the first demonstration of such specificity of arousal system function and has implications for understanding the motivational and circadian consequences of arousal system dysfunction.

What’s even more interesting, though, is that there’s a second half to this story – the dozy mice were perfectly perky in the dark:

We found that Hcrt knock-out mice were unable to work for food or water reward during the light phase. However, they were unimpaired relative to wild-type (WT) mice when working for reward during the dark phase or when working to avoid shock in the light or dark phase.

In other words, the mice without hypocretin stayed awake and worked for food just fine when the lights were out. So they probably have promising futures as bartenders or bouncers.

The takeaway here is that hypocretin isn’t so much responsible for enabling knee-jerk reactions as it is for helping mice (and us) stay alert and motivated to complete reward-based tasks when the lights are on. Without this hormone, we might act normally at night, but we just wouldn’t feel like staying awake when the sun was out.

And that’s exactly what Siegel’s team had found in several of their earlier studies, which linked human hypocretin deficiency with narcolepsy – a disease that causes excessive sleepiness and frequent daytime “sleep attacks.” These new results suggest that narcoleptic patients might have more success getting work done during the night, when their symptoms might be less severe.

Siegel also thinks clinically administered hypocretin might help block many effects of depression, and allow depressed patients to feel more motivated to get up and about during the day. If so, this could be a promising new form of treatment for that disease as well.

Finally, and perhaps most intriguingly of all, it’s likely that similar hormonal response “gateways” play crucial roles in other neurochemical arousal systems – like those involved in fearanger, and sexual excitement. If so, discoveries along those lines could provide us with some staggering new insights into the ways our brains regulate their own behavior.

So, I know what you’re probably wondering: am I really advocating the use of electric shocks to keep bored math students awake? Of course not – I think releasing wild badgers into the classroom would be much more effective.

Take Your Time

Stimulating a certain brain region makes people take less time to consider their decisions, a new study reports.

"Can I eat a whole jar of cookies? Only one way to find out!"

One particular area of the frontal lobe – the medial prefrontal cortex (mPFC) – is involved in helping us take conscious control over our decision-making process. While the mPFC is stuck on a problem, an ancient brain structure called the subthalamic nucleus (STN) slams the brakes on other brain activity, allowing us to think without acting impulsively.

By applying electrical stimulation to the STNs of volunteers, researchers found they could shorten the time it took for them to come to a decision – and lessen the amount of evidence it took to make them lean one way or the other.

As the journal Neuron reports, a team led by Brown University’s Michael Frank set out to better understand how the process of impulse control works on a neurophysiological level. Though the mPFC’s role in decision-making has been fairly well studied, Frank suspected that other brain areas might jump in to help control impulses when the mPFC was especially busy.

Frank had previously worked with patients suffering from Parkinson’s – a disease known for the impulsive movements it causes – and had noticed that a treatment called deep brain stimulation (DBS) helped suppress those movements by stimulating the STN. So he set out to explore this connection further:

To test that theory for how areas of the brain interact to prevent you from making impulsive decisions … you have to do experiments where you record brain activity in both parts of the network that we think are involved. Then you also have to manipulate the system to see how the relationship between recorded activity in one area and decision making changes as a function of stimulating the other area.

To do this, the team selected 65 healthy volunteers and 14 subjects with Parkinson’s. The volunteers lay in an fMRI scanner as the researchers showed them pairs of simple images, and asked to choose one image from each pair – some images resulted in rewards, while others didn’t.

The researchers noticed that mPFC activity was especially high when the volunteers were choosing between two images carrying equal rewards. But when the researchers used DBS to stimulate the STN in Parkinson’s patients, they reached their decisions much more quickly – even though their mPFC activation was as high as ever:

Trial-to-trial increases in mPFC activity … were related to an increased threshold for evidence accumulation (decision threshold) as a function of conflict. Deep brain stimulation of the STN in individuals with Parkinson’s disease reversed this relationship, resulting in impulsive choice. In addition, intracranial recordings of the STN area revealed increased activity … during these same high-conflict decisions.

In other words, the researchers could directly influence the decision-making time of volunteers by turning DBS on and off.

Aside from the obvious implications for supervillain technology (perhaps in a mind-control plot that also involves using magnets to make people lie), scientists hope this breakthrough may help DBS designers create systems that take mPFC activity into account, to replicate a healthy relationship between the mPFC and the STN more accurately.

And for the rest of us, I’m pretty sure this means, “My STN made me do it” is now a perfectly valid legal defense.

Working Off Worry

Want to get rid of gloomy thoughts? Try working some physical activity into your daily routine, says a new study.

Even adorable kitties need an endorphin boost sometimes.

For people who struggle with depression and anxiety, the research shows, exercise can be just as effective as antidepressant medication. It often prevents symptoms from getting worse – and in some cases, it even helps cure the problem.

Doctors have known for decades that a little physical activity can help distract you from your worries, boost positive feelings, and even relieve anxiety and depression. But in recent years, research has shown that exercise’s hidden effects reach much deeper: it tells your body to produce endorphins – natural chemicals that act similarly to morphine - to produce a natural high. And studies have shown that regular exercise can even make you smarter, by increasing blood flow to the brain and triggering neurogenesis – the birth of new neurons.

But as this new paper in the Journal of Clinical Psychiatry reports, a team led by UT Southwestern’s Dr. Madhukar Trivedi has discovered something even more exciting – a regular dose of exercise can work just as well as antidepressant medication:

Many people who start on an antidepressant medication feel better after they begin treatment, but they still don’t feel completely well or as good as they did before they became depressed. This study shows that exercise can be as effective as adding another medication.

In other words, patients who exercised instead of adding a second drug often improved just as much as people who did add another drug.

By the time the 12-week study was finished, almost 30 percent of the patients who exercised had achieved full remission of their depression, and another 20 percent showed significant improvement. That’s close to 50 percent of depressed patients whose moods measurably improved thanks to exercise.

It’s also intriguing that different types of exercise seem to have different effects on people with various characteristics:

Moderate exercise was more effective for women with a family history of mental illness, whereas intense exercise was more effective with women whose families did not have a history of the disease. For men, the higher rate of exercise was more effective regardless of other characteristics.

So if you’re a woman with crazy parents, you might benefit most from a quick jog on the treadmill – but it looks like I’m gonna have to run a Warrior Dash if I want to stop sulking.

Anyway, the good news is, it doesn’t take much of an investment to start seeing the benefits of exercise – most doctors recommend somewhere between 30 and 60 minutes, three times a week. Even taking a short walk on your lunch break can cheer you up.

Unless you’re perambulating on one of these things – I don’t think that counts.

Mind Control

A comfy new “brain cap” will soon allow users to remotely control robots with their thoughts.

The new UMD brain cap is as stylish as it is functional.

By “comfy” I mean “noninvasive” – instead of sticky electrode patches or needles, the cap uses sensors embedded in its fabric to detect electrical signals along the scalp. Just slip it on, and you can start surfing the internet – or (probably eventually) remote-control a giant battle robot – using only the power of your mind.

A study published in the Journal of Neurophysiology shows off the results of the brain cap’s latest human tests, conducted by the University of Maryland’s José ‘Pepe’ L. Contreras-Vidal and his team.

The team’s first study focused on using these electroencephalography (EEG) caps could to translate brain activity into a sort of mental mouse, which allowed users to control a computer cursor with their thoughts after a short training period. The next round of experiments studied the neural correlates of hand movements, and allowed the subjects to turn and flex a 3-D rendering of a hand just by thinking about those motions.

But this new study aims to take this technology to a whole new level:

Angular kinematics of the left and right hip, knee and ankle joints and EEG were recorded, and neural decoders were designed and optimized using cross-validation procedures. Our results … suggest that EEG signals can be used to study in real-time the cortical dynamics of walking and to develop brain-machine interfaces aimed at restoring human gait function.

In other words, subjects may soon be able to control a pair of mechanical legs just by thinking about walking. This could be a helpful shortcut for the walking-robot industry, because it would allow the patient’s natural sense of balance to make the thousands of tiny adjustments needed to stay upright on uneven terrain.

This technology has been grabbing a lot of attention, and millions of dollars worth of grants have been pouring in from partners like the National Science Foundation (NSF), the National Institutes of Health (NIH), and respected medical schools and research centers across the country.

The benefits for people with paralysis or limb amputations are obvious, but an even more intriguing set of results focuses on patients who’ve suffered strokes:

“By decoding the motion of a normal gait,” Contreras-Vidal says, “we can then try and teach stroke victims to think in certain ways and match their own EEG signals with the normal signals.”

In other words, the team hopes to take advantage of the brain’s natural synaptic plasticity to retrain patients’ thought patterns to produce the right movements. This could allow them to regain use of their limbs, and perhaps even walk again, without needing surgery or permanent prosthesis of any kind.

If all goes as planned, the future may look brighter than ever for patients who’ve lost the use of an area of their body. Though many of today’s therapies still depend on invasive techniques like surgery or implants, the next wave of technologies could allow intuitive systems like the UMB brain cap to reshape the brains – and even the bodies – of patients who have the will to learn a new skill.

Memory Lost & Found

New research has unlocked some reasons why memories weaken as we age – and more intriguingly, it suggests that the process can be reversed.

Forgetfulness is unpleasant for adorable kitties too.

According to a study published in the journal Nature, a large part of this decline is due to the chemical environment of neurons in the prefrontal cortex (PFC), an area of the frontal lobe that plays a large part in maintaining working memory – the ability to keep an idea, sound, or image “in mind” while we’re not directly perceiving it in our environment.

As we age, a chemical called cyclic adenosine monophosphate (cAMP), which normally is involved in intracellular signaling, piles up in the prefrontal cortex to the point that it actually slows the firing of a certain type of neurons, known as ‘DELAY’ neurons, which help maintain working memory.

But by introducing cAMP-blocking chemicals into the prefrontal cortices of macaques, a team led by Amy Arnsten of Yale’s Kavli Institute for Neuroscience were able to bring back these neurons’ youthful firing speeds:

PFC persistent firing with advancing age … can be rescued by restoring an optimal neurochemical environment. … Recordings showed an age-related decline in the firing rate of DELAY neurons, [but] the memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling.

This is still very early research, but the results are encouraging: inhibiting cAMP – or blocking the ion channels it uses – may become a promising treatment for people suffering from forgetfulness:

One of the compounds that enhanced neuronal firing was guanfacine, a medication that is already approved for treating hypertension in adults, and prefrontal deficits in children, suggesting that it may be helpful in the elderly as well.

Though neuroscientists – and plenty of other people – have known for centuries that age leads to a decline in various types of memory, the neurochemical basis for this decline remained poorly understood until very recently.

However, as scientists began to understand the connections between the PFC and working memory decline, they realized that the problem was closely linked with DELAY neurons’ firing rate – DELAY neurons in younger subjects fired more quickly during working memory tasks, while those in older subjects were much slower, which made them far less efficient in transmitting their messages.

This study marks the first definite evidence of a specific molecular problem underlying this slowness, and also the first strong indication that an effective treatment may be possible. The only caution, Arnsten points out, is that the treatment is unlikely to be effective for those suffering from Alzheimer’s or other forms of senile dementia, where neurological damage is often much more severe and widespread.

Even so, Arnsten says the treatment is already preparing to move to the clinical trial stage, meaning that aging patients may soon have a second shot at youth – at least as far as memory is concerned.

Narrative Medicine

Storytelling is more than just entertainment – new research shows that creating narratives can lift our moods, and even fight the symptoms of diseases like Alzheimer’s.

Orson "I Am Orson Welles!" Welles, unleashing his formidable narrative powers.

A group of neuropsychiatric researchers at the University of Missouri’s Sinclair School of Nursing tested a storytelling program called TimeSlips on nursing home patients suffering from senile dementia, the journal Nursing Research reports. Instead of focusing on factual memory, the TimeSlips method focuses on asking a group open-ended questions, to encourage imaginative brainstorming:

TimeSlips stories spring from hour-long, group storytelling workshops with people with memory loss.  A facilitator begins a workshop with a provocative image, invites creative responses, and weaves all answers – from the profound to the non-sensical – into a story.

Though this research is still in its early stages, the results so far are exciting – for weeks after a session, participants display improved communication skills, are more eager to start conversations, and say chatting with others is a more pleasurable activity than before. What’s even more incredible is that these improvements occur whether or not the patient can remember the storytelling session.1

The TimeSlips program is similar to an emerging – and still controversial – set of ideas known as narrative medicine. Unlike the freewheeling narratives developed in TimeSlips sessions, the field of narrative medicine is based on the concept that by crafting a meaningful story about a patient’s illness and path to recovery, it’s possible to improve that person’s chances of actually achieving that recovery:

It’s hard, sometimes, to give a simple definition, but in a diagnostic sense, the label of “sickness” becomes secondary to the life of the person who has a particular sickness. In order for a person to get well, there has to be a story, one that everyone believes, that leads the individual back to health.

Though this may sound like fringe science, schools as prestigious as Columbia University are now offering master’s degrees in narrative medicine. It makes more sense when you consider this method in another context – it’s essentially a placebo effect without the pill. To a certain extent, belief in a treatment’s effectiveness increases its actual effectiveness.

It also seems to point to a more underlying principle: the way our bodies respond to the world depends largely on our perceptions and expectations about how the world works. When we modify those interpretations – consciously or otherwise – we reshape our bodies’ responses as well.

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1. This is one manifestation of what’s known as procedural memory – essentially, memory for how to perform a task. Patients with severe amnesia (such as Alzheimer’s sufferers) can form and retain new procedural memories about as well as healthy subjects, despite the fact that they have no memory of the actual learning process.

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