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The Electric Brain
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NOVA: How else can consciousness get damaged?

Llinás: The other thing that can happen is that deep in the brain there is a structure called the thalamus. If the thalamus is damaged—and this is a central entity of the brain, some sort of gateway into the brain—if the gate is damaged then you have the same problems that you have with cortical damage. If the part of the thalamus that connects to the visual cortex is damaged then you don't see.

NOVA: So externally they'll look like the same problem, or for the person they will feel like the same problem?

Llinás: Absolutely the same. Even a neurologist cannot tell the difference, so he or she will have to do an MRI to see where the lesion is, either cortical or thalamic. So this central nucleus, the thalamus, and the cortex seem to be very deeply related. Consciousness can be damaged at the cortex, at the thalamus, or at the connections between the thalamus and the cortex. These two levels are organized as a feedback system in which the thalamus speaks to the cortex and vice versa in a dialogue.

The cortex, also known as "gray matter," is a thickly folded band of tissue responsible for higher mental functions. It is connected to the thalamus, shown here in green, an older structure in the center of the brain.
NOVA: If the thalamus and the cortex weren't able to "bind" all these different sensory inputs, what would the world look like?

Llinás: It wouldn't look like anything. It would be a hodgepodge of things, like when people drink too much and get into problems of timing and cannot move properly or think properly and see things that might not be the way things actually are. You can also have binding problems in neurology. A German colleague told me about a patient diagnosed as having a psychiatric condition. When they did a brain scan they found that she had a bilateral lesion on the temporal lobe. The problem was that she couldn't see things that were in motion, so things were continually appearing and disappearing. If she had to cross the street she would be terrified because she wouldn't see cars coming.

NOVA: Until they stopped.

Llinás: Yes, but then they just appeared, and where did they appear from? So she had a problem of binding movement with objects. There are issues of binding that are less complicated. For instance, some dyslexic children have binding problems and so their timing is slightly off, they think a little slower. To them everyday events happen a bit too fast for them, a bit like action movies, so they have problems following fast events or reading or even hearing the sounds of words properly.

NOVA: This goes back to the concept of the brain's need for rhythm?

Llinás: You need rhythm to put everything together. It is like dancing. Rhythm tells you when to move and at what speed to move, whether you are dancing a waltz or doing the cha-cha. Likewise the brain has a rhythm. In order to bind things many parts of the brain must fire and be active together, and they must have a rhythmicity. By having this rhythmicity—the thalamo-cortical rhythm—they make one function into an event.

"Consciousness is soluble in a local anaesthetic or even in alcohol."

NOVA: Is the binding, this rhythm, where consciousness comes from?

Llinás: Yes. Binding allows the different parts to be transformed into one cognitive experience. Now, interestingly enough, all of these things can be dissolved with a local anaesthetic. So if we put a local anaesthetic in someone's visual cortex, although we are not damaging the brain or changing the synapses or the neurons, the neurons are now not capable of having electrical activity. That function disappears. So consciousness is soluble in a local anaesthetic or even in alcohol.

NOVA: How is this thalamo-cortical rhythm generated?

Llinás: The cells in the brain, like the heart, have intrinsic rhythm. They move, they oscillate, like the waves in the ocean at a certain speed, a certain velocity, a certain frequency. Cells can have different frequencies. They can oscillate very slowly, and when that happens consciousness disappears. You are asleep, deep asleep; you are not dreaming. Cells are negatively charged; they are negative with respect to the outside world, by about 60 to 70 millivolts. If the membrane potential, the voltage across the membrane of the cells, is modified so it becomes a little less negative, the rhythm of the cells changes. They wake up. They oscillate at a high frequency.

NOVA: When you are asleep, how many times per second do the cells oscillate?

Llinás: When we are asleep most neurons oscillate at a very slow rhythm. That's how cells control consciousness—by voltage, by becoming electrically inactive or active. If you take a drug, if you fall asleep, if you get hit in the head, the brain does not generate the functional state that is you. The you disappears.

"I tell my students when they fall asleep that they disappear."

NOVA: Your image of yourself disappears.

Llinás: Yes, but to you that's all that being you is! I tell my students when they fall asleep in my lecture that they disappear. Their body is there but they're not there. As someone gently elbows them on the ribs they reappear. This is known as waking up.

NOVA: If the thalamus is so important in maintaining consciousness, can you trace specific psychiatric or neurological disorders to problems in the thalamus?

Llinás: This is a beautiful story that is just beginning to be understood now because it is such a different point of view. Because of these rhythms, which are known to be related to the sleep-waking cycle and which we have been studying since the beginning of the last century, we ask certain questions. I ask, for example, isn't it incredible that we fall asleep as a single entity and then wake up as a single entity? It would be a tragedy if you were to wake up and you could see but you couldn't hear. The system seems to be able to shut itself off as a whole and turn itself on as a whole.

NOVA: What would happen if for some reason some part just stayed off?

Llinás: If you look at Parkinson's patients, they have a great deal of difficulty moving. They are almost paralyzed—they walk with very small steps, have very little facial expression—and they have tremors. It turns out that their thalamic cell properties make these cells oscillate at a low frequency—four to six times per second—even when they are awake. One part of the brain is asleep while the rest of the brain is awake. That is a problem. These neurons are not dancing the right way. There is friction between neighboring areas, one of which is asleep and one of which is awake. Something called the edge effect apparently occurs, that is, there is a discrepancy. Some parts are stuck in a particular mode while the rest are computing other things. We came to the conclusion that in Parkinson's the inability to move in a coordinated manner was created by the fact that the frequency of oscillations did not allow for generation of proper movement orders to the muscles. And the edge effect, in contrast, was a continuous order to move.

NOVA: The edge effect—the continuous order to move—causes the tremors?

Llinás: Yes. And if that is the case then if you wake up the appropriate part of the thalamus this problem should disappear. If you put an electrode in the part of the thalamus that polarizes it, this problem should immediately disappear.

NOVA: And this has been tried?

Llinás: Yes, we have spectacular films of such results. You can see how when the person is stimulated the results are immediate and the person begins to function. You are bringing the circuit back into the correct timing by either returning the cells to their correct rhythm or by taking them out of the loop. So, the question is, what happens if that occurs in another part of the thalamus? What about focusing on a part that hears? What you would expect to happen happens—the edge effect now produces a sound, rather than a tremor. And what property does this sound have? It is on all the time. It has a certain ongoing frequency, like a persistent acoustic tremor. The person hears something not from the outside but from a signal on the inside. This is the case in tinnitus.

Ear Tinnitus, more commonly known as "ringing in the ear," occurs in millions of people. People suffering from this condition hear a sound even when no external sound is present.

NOVA: Ringing in the ear?

Llinás: Right. So what happens if something like this happens in a part of the brain that feels pain—the cingular cortex? What happens is that you have central pain. Like when you lose an arm but the hand that should be there hurts, you have a phantom limb. [For more on phantom limbs see From Ramachandran's Notebook.] If you put in an electrode, and you stimulate the correct part of the thalamus, you get rid of the pain. And what happens to depression? Same thing. Hallucinatory events in the visual system are probably the same thing too. So there are a whole lot of psychiatric and neurological problems that might be related to a thalamo-cortical dysrhythmia.

NOVA: Do you think that someday you might be able to insert electrodes in the appropriate part of the brain to solve all these different problems?

Llinás: Well, hopefully it is only a temporary solution while we think of better ways to solve the rhythm problem. A pacemaker with an electrode is a very rough solution.

NOVA: Most people, it seems, don't view the brain as electric—they view it as a big gland secreting neurotransmitters. So that if you have an imbalance of serotonin you might have depression, or if you don't have enough dopamine, you have another problem—Parkinson's. How do neurotransmitters fit into your view of the brain?

Llinás: Dopamine and serotonin work by modifying directly and indirectly the electrical activity of neurons. Too much or too little generates medical conditions. With Parkinson's there is no dopamine. What happens then is that the thalamus becomes hyperpolarized and starts firing continuously. In the case of Parkinson's, dopamine goes down, and then the thalamus begins to oscillate, and you get tremors and paralysis.

NOVA: What other diseases might involve this timing problem, or lack of rhythm, between the thalamus and the cortex?

Llinás: We think that this thalamo-cortical dysrhythmia is responsible for some types of epilepsy, Parkinson's, depression, obsessive-compulsive disorder, some aspects of schizophrenia, central pain, and tinnitus. They are all part of the same disease.

NOVA: And you think this because you have seen evidence of it?

Llinás: Yes.

During an EEG, electrodes are placed on the scalp to detect electrical impulses within the brain.
NOVA: How do you actually view these rhythms?

Llinás: You can either put the patients in an instrument, like an EEG [electroencephalogram], or better an MEG [magnetoencephalograph], or else you can put electrodes in the thalamus during surgery and see abnormal activity.

NOVA: Supporters of biofeedback therapy have cited your work as support for their theories of why biofeedback could work in treating epilepsy. Does that make sense to you?

Llinás: It makes a lot of sense. With biofeedback, though, there's only so much you can do. If someone had enough of an intact brain to reorganize, then there would be hope. The best way to correct these things is with specialized designer drugs that would go to specific cells and change the properties.

NOVA: But there aren't many of those.

Llinás: Not at the moment, but rational drug development in neuropharmacology will result in some, at some point in the near future. We will dream some up. But you have to know what the problem is first, right?

NOVA: So what is coming out of this research is not necessarily pacemakers for the brain but more targeted drugs?

"Pacemakers aren't my idea of heaven."

Llinás: Pacemakers aren't my idea of heaven. It's the same with cancer treatment. These are molecular problems, and we are attacking them with spoon- or toothpick-sized tools. Obviously it's wrong, but that's all we have. Rational drug design is what's going to happen. At the moment we use drugs that hit everywhere, and so they have unwanted side effects. There are bad side effects to neurosurgery too and to having cables coming out of your head. There are side effects in all of these things we do.

NOVA: Does the normal thalamo-cortical rhythm change as you grow older?

Llinás: Yes, we have looked at that. Forty hertz [number of cycles per second], or beta gamma band activity, as it's known, is not as well organized with age. There are low frequencies that begin to creep in. So people don't hear so well, they have a little ringing in the ears, and they don't see so well. You begin to see how the ability to put things in time very crisply disappears. A 25-year-old is agile, intelligent, sees things better, and can memorize and remember better. He has the disadvantage of not having experience, hence the saying, "if only the young knew or the old could." The young don't know but they can and the old know but they can't.

Neuroscientist Rodolfo Llinás
NOVA: What do you think about this work that has come out recently that suggests that the brain is always generating new neurons?

Llinás: It's a bit controversial. I haven't seen many people getting better with time. There's a very good reason for it, by the way. The nervous system has its own developmental history. Most of the nerve cells are as old as we are, and they have known one another for as long, so they have established their connectivity—they have a common history. So if a new cell comes in, forget about the new-kid-on-the-block problem. How are you going to give functional context to that cell?

The nervous system doesn't repair itself for a very good reason. It lacks context if it starts growing in all directions. A paralyzed leg is a big problem, but worse than a paralyzed leg is one that moves in the wrong direction or at the wrong time. That one can easily kill you.

NOVA: Do you find, spending so much time thinking about how the brain thinks, that it's hard, even when you're not at work, to stop thinking about how how your brain thinks?

Llinás: Sure. I find such thought fascinating and often downright amusing. Esthetically the brain has been beautifully assembled by evolution, and it's also, fundamentally, about the nature of our own existence.

This interview was conducted by Lauren Aguirre, Executive Editor for NOVA Online.

Photos: (1-2,5,7) Photo Researchers; (4) Corbis Images; (6) Rob Meyer for WGBH; (8) Courtesy of Rodolfo Llinás. Video Clip: David A. McCormick, Yale University

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