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Brain Mapping: Possible Road To A Cure

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LOS ANGELES, Calif. (Ivanhoe Newswire) - We know maps can lead us to some of our favorite destinations, but did you know they may also put us on the road to better health? Now, new research in brain mapping may help find treatments to some of the most common neurological and memory disorders.

Dr. Mayank Mehta is one of a number of researchers at UCLA studying the secrets of the human brain.

"We hope this could help us understand what goes wrong in Alzheimer's disease," Dr. Mayank Mehta,  Professor of Neurology, Physics, and Astronomy at UCLA, told Ivanhoe.

Mehta mapped neuron patterns that form when rats do simple tasks in hopes of learning more about how different sections of the brain communicate.

"The brain has its own dynamics, its own laws of physics.  If that goes wrong, clearly it will play a role in loss of memory, such as Alzheimer's or PTSD," Dr. Mehta explained.

Diseases that Dr. Arthur Toga says may one day be treated with targeted therapies using brain mapping.

"Our ability to look at a living brain of an individual that has a disease, or has had a traumatic brain injury, has allowed us to target exactly what has happened and suggest various therapies," Arthur Toga, Director of the UCLA Laboratory of Neuro Imaging, told Ivanhoe.

For the first time, Dr. Toga's team has mapped the progression of Alzheimer's in the brain.

"The net result is almost a four dimensional map showing you the trajectory of loss of tissue," Dr. Toga said.

While understanding and unlocking the secrets of the brain may take many years, researchers say it will be worth it when those secrets lead to treatments and possible cures. Submit

"Well, every few months is a bigger breakthrough," Dr. Toga said.

Researchers said they'd eventually like a large library of brain maps that will help them compare brains of people who suffer from similar diseases. This library will help doctors across the world give personalized treatment to each patient.

RESEARCH SUMMARY

BACKGROUND:  Alzheimer's is the most common type of dementia that causes problems with memory, thinking, and behavior.  It is not a normal part of aging, although aging is the greatest risk factor.  Up to five percent of people with the disease have early onset, which appears when someone is in their 40s or 50s.  However, it is a progressive disease that gets worse over time.  In early stages, memory loss is mild, but with late-stage Alzheimer's individuals lose the ability to carry on a conversation and respond to their environment.  It is the sixth leading cause of death in the United States.  Patients with Alzheimer's live an average of eight years after their symptoms become noticeable to others.  However, survival can range from four to twenty years, depending on age and other health conditions.  (Source: www.alz.org)

ALZHEIMERS'S & THE BRAIN:  Changes in the brain begin long before the first signs of memory loss.  The brain has 100 billion nerve cells.  Each nerve cell connects with others to form communication networks.  Groups of nerve cells have special jobs, some of which are involved with learning, thinking, and remembering.  Others help with hearing and smell.  Brain cells operate like tiny factories.  They receive generate energy, supplies, construct equipment, and get rid of waste.  Cells also process and store information and communicate with other cells.  Researchers believe Alzheimer's disease prevents parts of a cell's factory from running well.  As damage spreads, cells lose their ability to do their jobs and eventually die, causing irreversible changes in the brain.  (Source: www.alz.org)

NEW TECHNOLOGY:  There is not a cure for Alzheimer's, but there are drugs and non-drug treatments available that can help with cognitive and behavioral symptoms.   Researchers are looking for new treatments to alter the course of the disease and improve patients' quality of life.  Now, researchers at UCLA have been developing this brain mapping project.  "This is a project born of frustration, basically. For many years, all of us who study brain structure and function have struggled with the fact that no two brains are the same — not in shape or size and certainly not in function," Dr. John Mazziotta of the International Consortium for Brain Mapping, based at the University of California, Los Angeles, was quoted as saying. "But how different they were and how to compare them was not known."  They have been collecting brain images from all sorts of people living in seven nations on four continents.  The brain atlas maps the brains in multiple dimensions.  It charts brain activity.  (Source:http://www.nbcnews.com/id/3077071/ns/health-alzheimers_disease/t/brain-atlas-seeks-define-normalcy/)

INTERVIEW

Dr. Mayank Mehta, Professor in the Department of Physics and Astronomy, and the Department of Neurology at UCLA, talks about new research in brain mapping that may help find treatments to some of the most common neurological and memory disorders.

How long have you been studying the brain?

Dr. Mehta: I have been studying the brain for more than fifteen years.

When did you move into the virtual maze type of thing?

Dr. Mehta: Around the time I moved to UCLA. Long ago my interest was understanding the structure of physical space time, which was studied in physics by people like Einstein and Newton. We wanted to see how space and time arise in the brain. For example, I can ask you to focus on an abstract point in space, and after a half an hour and you'll be able to still find it. There's nothing there at that abstract point, there's no light, there's no sound, or smell, but you can still point to it. So what is that ‘space'? All animals perceive space naturally. But, to understand how we perceive space, we should be able to manipulate space. So how do we manipulate space to understand how the brain processes? You make virtual reality!

That's what you're doing?

Dr. Mehta: More than two years of hard work by these students and postdocs in our labs, we have a fully functional multi-sensory and noninvasive virtual reality system here.

What can you see through this that you couldn't see before?

Dr. Mehta: The really interesting thing is that when the space is going on, real space that we are in, we cannot manipulate it. The real space is made up of a lot of things. Real space is defined by the lights in the room clearly, but it's also defined by smells, sounds, stuff on the floor, so we don't know how the brain puts all this together. Now if we make virtual reality we can control each one of these precisely. We can make the virtual space go faster, we can make the space go slower, and we can make the space go backwards. We can make the rat jump through hoops or we can make him jump through worm holes. We can now create all kinds of spaces and understand how our brain puts together these different changing stimuli to create space. This was not possible before.

Can you see then how the brain perceives space?

Dr. Mehta: Yes. We have now developed technology to look inside the brain while the rat is doing this virtual world task. Since we have control over the space that we have generated, we now know what he is seeing because we have it under our control. That tells us pretty profound things about what's going on in his brain and how space is being put together.

What can you see happening in the mouse brain?

Dr. Mehta:  It turns out there is a part of the brain, called the hippocampus, which is critical for learning and memory. It's one of the oldest parts of the brain; it's literally called the old brain. Now it turns out as the rats, mice, or even humans start walking around in the real world or in virtual space, like playing a little video game with an avatar, there are neurons in the hippocampus which will fire at different places in that virtual world as if they have a map of the virtual environment or the real world. The question now becomes how did this brain map of space arise? The map arises pretty much in the very first trial. A human being or a rat gets into a virtual world or a real world and within seconds there is a map. It's fascinating.

Let's say the map was a real map; before you had the United States and now you're putting in the roads, is that right?

Dr. Mehta: There is not even a map because before you came to this room you didn't know how this room would look, where the table would be, where the chairs are; you didn't know that, but you figured out that map instinctively as soon as you came in. We take it for granted, but it's really hard to even teach a powerful computer to make that map.

Now you're making all the connections?

Dr. Mehta: To some extent. It goes in both directions. On one side if I were to ask you to describe what the map of the room is you'd point to different things. You would say there is a wall here, a plant there, a table somewhere, the sound of a water fountain, fragrances from the kitchen… The question is: how does your brain put it all together to make a map and the perception of a room? Now that's a non-trivial process.

When you say a map, when I walk through the door I instantly know to step around that chair and that desk, and that's the map?

Dr. Mehta: Exactly. That's the map, your layout of the world. It's the map that you're figuring out on the fly, and all animals have to do that.

So, we don't know how they do it?

Dr. Mehta: That's exactly right, and we are figuring out how that happens. They have two parts to it. One is the stuff out there in the world. There are a lot of things out there in the world that define what's the map, buildings, mountains, sounds, smells, etc.  However, there is the stuff inside the brain too. There's a lot of interesting electricity and chemistry that goes on inside the brain; which has its own rules and rhythms. The match between the rules of the brain and rules of the world define space. It's pretty interesting.

Are you doing this by mapping neurons?

Dr. Mehta: Yes. We have been mapping the activity of lots of neurons simultaneously while the animals are forming maps of the world. Surprisingly, the formation of the map also depends on what goes on during sleep after you have formed the map. There's a huge amount of research which shows that the map you have formed during exploration is not the full story, it's only a part of the story. When you go to sleep, when you think you're not doing anything, that map is getting changed.

Is it taking everything that it's learned through the day?

Dr. Mehta: It seems like it. The process is called consolidation. It seems like what goes on is you're taking in what you learned during the day and what you learned in your life before that and consolidating all of that to generate a map.

Right now what has been the most surprising finding to you?

Dr. Mehta: The most surprising finding is that when these maps have been formed they are dynamic; that's number one. You think the world is the same as you're walking around. We did a very careful experiment and a rat walks in a very simple world; nothing complicated, his behavior doesn't change. Walks once, then walks a second time, in the same simple room on precisely the same path, and everything seems constant, unchanged. But already the brain's activity changes within one trial. Neurons become twice as active within two trials and neurons start to predict where the mouse is going to be based on just one experience. So in the first trial, the neurons are simply telling him you are next to the chair, you are next to the table, so on and so forth. Within one or two trials those neurons start to tell where you are going to be in a few steps, which is crucial for navigation. In other words the neurons were initially saying where you are but after a few trials they start to generate a mental image of where you will end up along the path, based on that brief experience. Put it simply, the neuron starts to predict your future position in space! If you're going anywhere you not only need to know where you are but you also need to know where you're going to end up. This is precisely what we found neurons are doing, very quickly. That's one surprising finding. The second surprising finding is that when these rats or humans are walking around, our brain's activity apart from having this map develops another interesting thing called rhythm. The whole activity of the space-mapping part of the brain becomes rhythmic. This rhythm is generated by the brain on its own!   We found very recently that this rhythm codes the speed at which you are going. So the faster you go, the bigger and faster is the rhythm. Even more fascinating is that very rhythm that gets bigger when you run faster is actually crucial for learning and memory and formation of maps of the world. If you're simply sitting and do some other mechanism, that rhythm became stronger and you would learn better. On the other hand, when you go to sleep the rhythm goes away.

So I should always walk on a treadmill and read a book?

Dr. Mehta: We recently did similar  experiment on a treadmill. We found that the rhythm does become bigger with increasing running speed on a treadmill, just like running in the real world, but the rhythm does not get any faster at higher speeds on the treadmill but it does in the real world. We are now working hard to understand why this happens and what does this do to learning and memory. .

From what you do here, will it have any impact on human brains of why Alzheimer's happens or memory loss?

Dr. Mehta:  We hope that this will help us understand what goes wrong in Alzheimer's disease. In another study that we just did which we published last year, we were looking at a part of the brain called the entorhinal cortex where the Alzheimer's disease starts. So, we were looking at the activity of those neurons when the rat was not doing anything; the rat was simply sleeping. You would think nothing should go on because he's not going anywhere. Turns out throughout the period of sleep there are these special neurons in the entorhinal cortex behave as if they were remembering something. Not just every now and then during sleep but for pretty much the whole duration of sleep. These neurons were behaving as if they were remembering something. Even more fascinating, this memory like activity in the entorhinal cortex was very powerful in driving the activity of map making neurons in the hippocampus. So now you can see the connection that there's this memory-like processes that are going on in the brain even when you're not actively trying to remember anything. The brain has its own dynamics and its own laws of physics or biophysics that govern what the brain is doing. Those things are processing stuff and if that goes wrong, clearly that will play a crucial role in loss of memory such as in Alzheimer's disease or PTSD where the memories are pathological. It's a long way off from here to Alzheimer's disease, but we're working on that.

Do you think we've got it?

Dr. Mehta: We are getting there, especially with the new technology we are now developing. In a few moments you are going to see two experiments that we are doing. One is the experiment where the rat is trying to find his way in a virtual world. Why virtual world? Because there we can control the stimuli provided to him to form a map of space, he cannot find his way based on some scent marks that he left on the track; that's one experiment. You're going to see the rat actually behaving in the virtual world, finding his way, getting a reward, being happy, falling asleep in the virtual world as his virtual nest, and behaving perfectly naturally except that he's not going anywhere in reality. He's fixed in one place the world is going by him but he believes he went to the world. Another experiment you are going to see is now instead of the rat being in one place and the world going by, the rat actually goes to different places so he can see there are differences. We can compare those two things. You're also going to see is how the brain signal looks when the rat is going somewhere in the real world or the virtual world, or even when the rat is sleeping. You'll see amazing patterns of activity come and go in the brain as a function of different behaviors. You'll be able to hear the activity of lots of neurons simultaneously while the rat is doing these things. 

FOR MORE INFORMATION, PLEASE CONTACT:

Mark Wheeler
Senior Media Relations Rep
UCLA Health Sciences Media Relations
mwheeler@mednet.ucla.edu

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