Thursday, April 19, 2012

I think, therefore I grasp

There is major interest in trying to “cure” paralysis and help patients overcome mobility limitations, trying everything from repairing damaged spinal cord neurons, to engineering human exoskeletons.  One branch of this research focuses on brain machine interfaces (BMI) in which a multi-electrode recording chip is implanted into the brain.  This array can “read” what the neurons in the brain are signaling.  It sends this information to a computer which decodes these signals into the intended action of the brain.  Normally these brain signals would travel down neurons in the spinal cord to the motor neurons that control muscle contraction.  During spinal cord injury, the pathways from the brain to muscles are damaged and non-functional.  With the array implanted in the brain, the BMI can bypass the damaged nerves and stimulate the intended muscles directly.  If the brain sends the signal to “flex right arm” then the implanted array and the decoding computer will interpret the intended message and stimulate the right arm muscles.  In time the patient will learn to control their own paralyzed arms by thinking about the movement, which is essentially what we all do anyway.  In the case of the BMI, there is an electrode array in the brain, an external computer and stimulating electrodes in the arm muscles to help get around the damaged spinal cord.

A paper was published online this week in Nature by Ethier et al. that used BMIs in monkeys to control hand grasp.  I haven’t read all the previous papers about BMIs, so I don’t know how much of an advance this is, but according to the authors, this is one of the first times that force of muscle contraction, as opposed to direction of movement was taken into consideration.  Their experiments worked very well and the paralyzed monkeys were able to grab balls.

Experimental set up
Multi-electrode arrays were implanted into two monkeys.  There is a region in the brain called the motor cortex which controls muscle movement.  BMIs only work because there are specialized regions in the brain devoted to different tasks.  The researchers put the arrays specifically in the area devoted to contracting the muscles found in the hands (i.e. for grasping movement).  The monkeys were totally functional at this point (not paralyzed), so they trained the monkeys to grab a ball and put it into a tube, while recording the neuronal activity in the motor cortex.  They mapped the brain activity associated with muscle contraction and movement until they were able to develop a model that could predict hand movement based only on the activity in the brain (amazing!)  While the monkey was thinking about moving, the model could predict quite accurately, in real-time, what kind of movement would happen in each muscle.

Next, they injected an anesthetic into the arm, so it was temporarily paralyzed.  When monkeys went through the trials where they had to grab a ball to get a treat, their brain activity showed that they were thinking about moving their hands, but they couldn’t actually move them because they were paralyzed.  The monkeys also had a series of stimulating electrodes implanted into their hand muscles.  Could the BMI be used to control hand grasping movements in paralyzed arms?

Brain-controlled grasping
The paralyzed monkeys were indeed able to grab the ball and place it in the tube just by thinking it.  Just to reiterate: the motor cortex of the monkeys was activated, this was recorded by the implanted array, which sent the signal to a computer, which interpreted the intended movement, which was finally achieved by implanted electrodes in the hand muscles.  

This is completely amazing.  It’s amazing that the computer model was accurate enough to predict hand movement just by recording activity of 100 neurons in the brain.  Both monkeys had about a 75% success rate of picking up the ball, which isn’t bad at all considering the fact that their arms were paralyzed and being controlled by a machine.

One of the monkeys also learned a different task.  The monkey was taught to squeeze a tube to make a cursor on a screen move to a target location.  The harder the squeeze, the more the cursor moved.  This task is all about modifying how hard to contract muscles and controlling the grasp, a fairly complex movement.  Again, they made a model to predict the amount of force based on the neuron firing pattern.  And once again, the monkey was paralyzed and was able to do the task without having voluntary control of its hand muscles.  As it completed the task, its muscles got tired (muscle fatigue), so it had to send stronger signals to them to contract.  The BMI was able to control the amount of force necessary to counteract the muscle fatigue, just like the fully functioning monkey would do. 

So where does this leave us?  It was only two monkeys, but the BMI worked so well, I imagine this would be true for others as well.  One problem is that their computer model was fine tuned by recording activity from the functioning monkey while comparing that to actual muscle movement.  This would be impossible to do in someone who is already paralyzed.  How well would they be able to adapt to a prediction model that isn’t designed specifically for their brain? 

The authors bring up an interesting point that the muscle stimulation would be helpful to maintain muscle and bone structures, and if the patients are associating that with a particular task, it might be more rewarding.  As they say, “it may be that drawing on a conscious process to restore natural movement will bring the additional benefit of improved psychological health.”  I just find it so impressive that we know enough about how the brain sends signals that we can tap into that to control machine-based movement.

UPDATE: This paper has officially been published in the print version of Nature and there is a companion article that shows that BMIs work in humans too!  Two paralyzed older people had multielectrode chips implanted into their motor cortices.  Instead of controlling their own arms, like the monkeys did, they controlled a remote operated robot arm.  The commands in their motor cortex were converted into a digital code that could tell the robot arm how to move.  One woman was even able to grab a bottle and bring it to her mouth and drink from a straw!  And this was after being paralyzed for 15 years.  It's amazing that her motor cortex is still functional after not being used for years.  Read the New York Times article about this research.

Wednesday, April 11, 2012


We have all heard about birds being able to sense the Earth’s magnetic field in order to navigate during migration, but how can they do that?  There have been a number of studies that implicated iron-rich cells in the upper beak of birds as magnetoreceptors.  Just like there are neurons that can sense mechanical stimuli, the idea was that the iron in these magnetosensitive neurons is affected by the Earth’s magnetic field in such a way that the neurons then become activated, signaling a change in the intensity of the field. 

There is no doubt that birds can sense a magnetic field, but a recent paper published online in Nature disputes that there are magnetosensitive neurons.  It’s unusual to find a paper based mainly on negative results published in a prestigious journal.  I like controversies in biology, so let’s take a look at this one.

First, the authors, Treiber et al., very systematically mapped the location of all the iron-rich cells in the beak.  You can find these cells by simply staining thin sections of the beak with a dye called Prussian blue, which labels ferric iron.  They found that the number and distribution of iron-positive cells was extremely variable from pigeon to pigeon of the same age and sex.  Sensing the magnetic field is very important to birds, so you would think there would be a near constant number and location of iron-rich cells, if these were in fact sensing the field.

In order for these cells to be acting as sensors, they would really need to be neurons and feed into the bird’s brain.  The authors stained the iron cells in the beak with markers for neurons and saw almost no overlap.  In other words, the iron-rich cells are not neurons.  Well, what are they then? 

Here's a macrophage engulfing some bad bacteria.
Macrophages are cells of the immune system.  They eat up bacteria and other pathogens and destroy them.  It turns out that macrophages also store iron that is released from hemoglobin when old red blood cells are recycled.  It makes complete sense, then, that the iron-rich cells in the beak could be macrophages just doing their normal storage job.  The iron-rich cells in the beak look like macrophages, but the authors confirm this by positively staining these cells for a macrophage-specific marker.  These cells are definitely not involved in sensing the magnetic field, since they can’t send signals to the brain.

This paper brings us back to square one: how do birds sense the Earth’s magnetic field?  All we know is that they don’t do it with the iron rich cells in their beaks.

UPDATE: Birds may not have magnetoreceptors in their beaks, but they do have neural correlates of magnetic fields in their brains.  In a recent report published in Science, researchers recorded from neurons in pigeon brains while varying a local magnetic field around them.  They found that individual cells in the brainstem would get activated when the magnetic field was pointing a particular direction.  Some neurons preferred 15 degrees, others 90 degrees, etc.  This is a strategy that the brain uses for other sensations, such as vision and audition.  Individual neurons are "tuned" to a particular stimuli.  We still don't know how birds are able to sense magnetic fields, but now we know that their brains are set up to interpret that information coming in from the mystery receptors.

Tuesday, April 10, 2012

The good, the bad and the noisy

I thought I would take a break from the complicated molecular pathways for a week and do an ecology paper.  It was interesting to read an ecology paper because it was written in a totally different style.  I made it half way through the methods section before I realized it wasn’t the results section.  The paper is by Francis et al. and was published in the Proceedings of the Royal Society B (what royal society?  B for Biology?  I think so).

The authors were looking at the effects of noise pollution on an ecological system.  Many papers have examined how increased noise can affect the behaviors of individual species, but this paper focuses on how changes in one species can alter the ecosystem.  The results are not surprising at all, but what I found most interesting were the methods.  There were two main experiments: one looking at hummingbirds and pollination, the other examining seed dispersal by scrub jays.

Noise increases pollination
Turns out hummingbirds like noise.  This may seem surprising at first, but lets think about it.  Have you ever heard a hummingbird sing?  Vocalization doesn’t seem to be that important to them, so from their perspective, noisy areas are good because it drives away their competitors and predators.  Since hummingbirds are important pollinators, it goes to reason that a noisy area would attract more hummingbirds, which would pollinate more flowers, leading to an increased population and diversity of flowering plants. 

How do the authors actually test this, though?  For all their experiments, they went to New Mexico, which has natural gas wells.  Some of these wells are quiet and some of them have noisy compressors.  This provides a great experimental setting where the only variable is noise, because the type of human activity and the vegetation features are nearly the same at all the wells.  In order to measure how often flowers are visited by hummingbirds and if pollination has occurred, the authors set up some artificial flowers.  In this way, they can control for random variations in flowers at the noisy wells versus the quiet wells.  From what I gathered from their description, they used pipettes filled with sweet nectar that was replenished each day.  They “decorated” the pipettes with colored tape to imitate the colors of flowers.  Yarn and colored tape?  That sounds fun!  The hummingbirds totally fell for it and started visiting the artificial flowers.  As expected, the hummingbirds went to the flowers near the noisy wells more often than the quiet control wells.

When hummingbirds visit flowers, some of the pollen (containing sperm) brushes off onto their bodies.  As they fly to a new flower, they bring the pollen with them, which may fall off onto the female parts of another flower, thus completing pollination.  To test if the increased visits to noisy wells would lead to more pollination, the researchers put fluorescent dyes onto some of the artificial flowers.  They followed the transfer of the dyes between different flower patches, and found that near noisy wells, more of the dye was transferred from flower to flower.  In other words, there would most likely be an increase in pollination of these flowers near noisy areas. 

Noise impairs seed dispersal
Many trees depend on animals to carry their seeds away to new environments where they can germinate.  For this experiment, the authors focused on the seeds of the pine Pinus edulis.

The authors scattered seeds under pine trees and set up motion-triggered cameras.  Every time a seed was removed, a photo of the culprit was taken.  They found that one species of mice preferentially took seeds from trees near the noisy wells.  The mice probably like noisy areas for the same reason as hummingbirds: less predators around (like owls).  Unfortunately for the pine, the mice mostly ate the seeds and didn’t help disperse them.  On the other hand, scrub jays collect lots of seeds, hide them and then forget about them; this is the optimal situation for the pine seeds, because they don’t get eaten and they get to grow in new places.  Scrub jays, unlike the mice, avoid the noisy wells, probably because they rely a lot on vocal communication.  The unhelpful mice are more prominent at noisy wells and the helpful jays avoid the noisy wells, so all this leads to decreased seed dispersal and fewer pine seedlings growing near the noisy areas.

Changes in the number of the hummingbird-pollinated flowers (positively) and pine seedlings (negatively) can have all sorts of other effects on the ecosystem near noisy wells.  As we all expected, noise may only affect one species directly, but it can have long reaching consequences for all the integral members of the environment.  Bad news in our industrial world.