Mind, Brain, and Behavior

Adolfo Plasencia:

Alvaro, in life, do we have to learn and unlearn?

Alvaro Pascual-Leone:

Undoubtedly! I reckon that is one of the greatest teachings of Eric Kandel’s marvelous work, and part of why he won the Nobel Prize. Learning is no longer just understanding the mechanisms of memory in the sense of how new memories are created but also how memories are forgotten, which memories should be forgotten, and, since Luria and many others, we now know that those who are unlucky enough never to forget, as is normal, suffer enormously from having an excessive memory. It is very important to forget.

A.P.:

You’ve done a lot of research using transcranial magnetic stimulation (TMS), a noninvasive method for stimulating the brain’s neurons, and you and your colleagues are trying to improve the situation of the ill or at least reduce the suffering from illnesses such as migraines, Parkinson’s disease, depression, and many more.¹

Can you explain what TMS technology is?

A.P.-L.:

First we have to ask ourselves what the brain is.

Generally speaking, we think of it as a complicated chemical organ inside the cranium. It uses different chemical substances to do different things. But above all, it’s electrical! The brain has as many neurons as there are stars in the Milky Way, and each of them is supported by and connected with thousands of other cells, which in turn are generators of electricity. The connections are like electrical cables. So, although it’s true that there are chemical substances in the brain and in the transmission of information between neurons, the brain is above all an electrical organ.

Hence the question: Is it possible to use electricity to modify the brain’s electricity and thus its activity?

The idea of using electricity to modify the brain’s activity is old, but it’s very difficult to do, because the skin and the cranium are wonderful insulators. If you want to put electricity inside, without opening the cranium and skin, it can hurt a lot! Even so, there are techniques still in use, such as electroconvulsive therapy for cases of depression. The patient, however, has to be anaesthetized, and a fairly strong current has to be applied.

Alternatively, you can open the cranium and directly stimulate the brain, as the pioneering work of Wilder Penfield clearly showed in Montreal in the last century. We can learn a huge amount about the organization of the brain thanks to this type of intervention, and I wanted to do the same, but without having to open the cranium and without being limited to patients needing surgical operations.

TMS is a technique that allows us to use a magnetic field to “make the bridge” between the current applied outside the cranium and the current that is induced in the brain. The bridge is created by the magnetic field, according to Faraday’s laws of induction. You pass a current through a coil and the current flow generates a magnetic field perpendicular to that coil. That magnetic field, as time passes, will induce a secondary current in any conductor suitably directed toward it. If you then position a coil of electric cable—copper, for example—and discharge a sufficiently strong electrical impulse, a perpendicular magnetic field is created; the magnetic field contrary to the electrical one can indeed penetrate skin and bone without problem and on arrival in the brain a current will be induced, as the brain is an electrical organ and a great conductor. That’s the principle.

Clearly, the difficulty is always in the details. What we want to do is stimulate a very specific point of the brain, and so coils of an appropriate geometry have to be designed to create well-focused electrical fields. We also need to know where to apply that electrical field in relation to the brain of the individual whose activity we want to modify or modulate.

All these technological problems can be solved and have mostly been solved over the last twenty years. Currently, we have very reliable techniques that allow us to stimulate areas of the brain the size of a fingertip or a pinhead, and to stimulate a specific point on the cerebral cortex in the convexity of the brain.

A.P.:

Modify here means to improve, doesn’t it?

A.P.-L.:

That’s another important point. Often when we think about what our brain does, when, for example, our hand is at rest, we know there are neurons that allow us to move the hand, and we assume that if we are not moving our hand, these cells are silent and doing nothing. But it’s not true! The neurons that move the hand are discharging 50, 60, 80 times per second but don’t cause movement because to cause movement, two things have to happen: those cells must increase their firing rate to about 110 times per second, and they must connect with specific other cells for a set purpose, and even modify the cell activity that normally exercises an inhibiting effect. It is always networks of synchronized cerebral activity that cause movement, a certain thought, and so on

We know we can modify activity in the neural networks in a controlled manner using, for example, transcranial stimulation. However, the consequences of that modification may be beneficial or harmful to the individual. So modifying doesn’t always mean improving. The challenge is to modify in such a way that the result is truly beneficial for the individual, and the acute effect may be different from the long-term effect.

A.P.:

Let’s move on to a mystery, namely, the functioning of the mind in the brain. Do you remember the verses of Calderón de la Barca:

“¿Qué es la vida? un frenesí.

¿Qué es la vida?, una ilusión,

una sombra, una ficción.

y el mayor bien es pequeño;

Que toda la vida es sueño,

y los sueños, sueños son.”

(What is life? A frenzy.

What is life? An illusion,

A shadow, a fiction,

And the greatest good is small;

For all of life is a dream,

And dreams are only dreams.)

I quote those verses of Calderón because of what you said about the brain creating its own reality in its interior, it being a formulator of hypotheses, a generator of expectations.

Why are you convinced of that?

Does the brain generate its own fictions, its own illusions?

A.P.-L.:

Absolutely! There are a lot of data in cognitive neuroscience and there is a lot of common knowledge about the fact that the brain is really a generator of hypotheses. The brain only sees what it’s looking for.

A.P.:

“Look” is not the same as “see,” is it?

A.P.-L.:

No, it’s not the same. There is a concept we call “inattentional blindness,” according to which if you’re attending to one thing and something else happens, you may not see it. The experiments I’m talking about are dramatic; for example, a study was undertaken where participants were asked to watch a group of six to seven people passing a basketball to each other and to count the passes. What nobody noticed was that someone dressed as a gorilla appeared on the court, turned, and passed! The participants didn’t see it! People are literally blind to what they do not have to look for. This is inattentional blindness. This type of cognitive experimentation shows that our expectations determine what we see and experience.

A.P.:

The brain concentrates on what it likes, and what it does not like, it rejects.

A.P.-L.:

It doesn’t necessarily focus on what it likes, but it fixes on something, on what it’s seeking, what it wants, what it likes or sometimes doesn’t like, but it has a series of expectations. The thing is, the brain does not face a situation without creating an expectation to compare it with. When reality doesn’t match that expectation, surprise and discord are generated. Mostly it fits. Everybody knows that! We all know that none of us turns out to be who we really are!

A.P.:

But Alvaro, when we talk about the brain, aren’t we talking about ourselves?

A.P.-L.:

Ah. That goes right to the heart of the question, whether the brain, the mind, and the soul are different things or not!

A.P.:

And if will has got something to do with it? The brain goes its own way and drags us with it. Are we its slaves?

A.P.-L.:

That’s a very difficult question!

On the one hand I am a convinced believer in quantum physics, where chance ceases to exist. The mind and what we are are a consequence of the brain and its structure. But the brain and its structure are also a consequence of the mind. According to Daniel Dennett, “the Mind, the Soul, etc. are emergent properties of the brain.” That doesn’t mean that the soul and the mind don’t exist as different realities. My godfather, Antonio Ferraz, is a philosopher, and one of his mentors, Xavier Zubiri, cites the example of watching television and says that the viewers who are watching see us and generate a hypothesis of what we are, and so we are a reality for them. Really, however, they are not seeing us but seeing phosphorescent or liquid glass points, pixels! However, their brain does see us! So there are two realities, both correct and both being captured at the same time. Just as in the verses of Calderón, the brain has an image of an inner life, of several dreams that are real and distinct from the hypotheses contrasted with outer life. From a neurological and physiological perspective, what is inside is important; one’s dreams are important because if those dreams are a consequence of and generators of other realities, that changes your brain. If you dream of greatness, you will be greater. If you have positive dreams, you will enjoy better health, be more hopeful. If you think about what you’re thinking you have to be careful because those thoughts are going to change your brain! And changes in the brain will change your reality. William James advanced such ideas when he said, “Believe that life is worth living, and your belief will help create the fact.”²

A.P.:

Be careful with your desires; they may come true!

A.P.-L.:

Exactly! And therefore, it’s important to realize that everything we do, think, experience changes our brain, even though we may not like the change.

A.P.:

You mentioned at a conference an experiment in which a group of randomly selected children at a school were sent and received the message that they were the best, the cleverest and, indeed, in the end, they were. It has also been shown that two individuals exposed to the same virus can infect each other or not, depending on the extent to which they are convinced they are going to become ill.

A.P.-L.:

What is really important in all this is to realize that when one thinks in a certain way or when one has an attitude or motivation, this induces changes of the nervous system, which in turn induce changes in health, in resistance to illnesses, or in success in daily life. This isn’t magic; it’s to the result of the activity of certain physiologically demonstrable connections in the nervous system. That’s why, when you believe you are going to recover, when you are aware of the situation you’re in from a health perspective and you’re sure the help you receive is the best, you get better.

The circuits that have to do with “feeling safe” generate a certain activity that sets substances free and make the leukocytes, the cells that defend us from illnesses, stronger. So there is an axis, a connection between certain cerebral networks and the immune system. That fails when, for example, you lose a loved one and see no reason to continue to live. And when there is no reason to continue to live, you’re more likely to become ill. Why is that? After all, we are constantly exposed to illnesses. We are literally continuously generating cancer. And yet most of us have sufficiently strong defense systems to kill off those cancer cells as they appear. Why, then, do we not always defend ourselves? Well, using the terminology of Susan Sontag, it’s because we are “cancerizing”; that is, it’s not the external agent that causes the illness: you have to have a bacterium that gives you the infection, but even that is not enough. Apart from that, there’s a series of host factors in ourselves that make us more or less prone to contracting illness.

Those factors are governed by our brain, dreams, thoughts, internal motivation, beliefs, and well-being. It is therefore very important to control the brain’s expectation chains, and this is possible because the cerebral networks of control are trainable.

A.P.:

Alvaro, another issue that concerns me is will.

Is it us that decides, or not?

Does our brain activate certain parts, certain circuits, beyond the will?

Does free will override external stimuli?

A.P.-L.:

Well, volition and free will pose problems in ethics and physiology, philosophy, psychology. As a physiologist, what I say is that from the physiological perspective, there’s no evidence that there is a change in the patterns of cerebral activity when facing decision making. What we do see is compatible with something happening and our brain generating an explanation. Rather than making a decision, it comes up with an explanation.

We still cannot identify the cerebral activity associated with intention, with decision making. It is as if cerebral activity was changing at random or by environmental influences, and our brain was continuously incorporating explanations of what was happening and generating a story from unrelated events.

The fact that physiologically we still have not found, and perhaps never will be able to see, evidence of free will and voluntary decision making doesn’t mean that those things don’t exist. All of us, I believe, know from experience that we can make decisions, that there is an “I” separate from the connections involved in the movement of a hand. The challenge, from the physiological perspective, is how to prove it.

What we do know is that we can change the knowledge of the decision we have made. For example, in one of the experiments we did, we said to the participants: You’ll see a light, and when the light comes on I want you, yourself, to make a decision, on whether to move your right hand or the left hand. Once the light goes off I want you to stick firmly to that decision until the light comes on a second time and then execute whatever you had decided.”

We showed that if you apply cerebral stimulation on certain frontal parts of the brain at a specific moment, the participant doesn’t decide, but “you decide” which hand to move for him, right or left, depending on where the stimulation is applied. We know this because the physiological pattern is fixed, so we know that we have done it. However, if we do it soon after the participant has had to make his or her decision, it is as if that decision had not settled in sufficiently, and the participant says to you, “This time I was very quick to move my hand!” and is convinced that she has made the decision, when actually you have induced the movement and she is interpreting it as something of her own volition.

A.P.:

They interpret it a posteriori, you mean?

A.P.-L.:

In this case, yes, but they are wrong. Clearly, our nervous system has an enormous capacity for interpreting things that happen to us, beyond our control, in order to make us think that we control them. But that doesn’t mean that situations where the brain may really control initiative don’t exist. By the brain, I mean “I.”

A.P.:

We also have to talk about intelligence.

Bertrand Russell wrote: “The difference between mind and brain is not a difference of quality but a difference of arrangement,” that is, of the organization of the parts of the brain.³ And for Marvin Minsky, the construction of a principle of intelligence can be made by starting with a fairly simple set of basic principles. It is the connectivity among them that generates the resulting complexity from which behavior arises. What do you think?

A.P.-L.:

I think that when we speak of intelligence, we are often referring to a fluid intelligence or what my uncle, Juan Pascual-Leone, calls “mental capacity.” We don’t refer to the activity of a specific neural network but to the capacity to activate neural networks that pass activity from one network to the other for a certain purpose—the motor of activity in neural networks. The great challenge for a neurologist or a neurophysicist is to discover what the neurobiological substrate of that capacity is that allows one person to have more and another person less and how we can—if we can—increase it.

A.P.:

Alvaro, don’t these technologies and means with which you are capable of penetrating and modifying the functioning of the human brain sometimes make you neurologists feel dizzy?

Are you going to be able to model the human soul, or am I going too far?

A.P.-L.:

The reason why I dedicate myself to this field is to increase skills that may be transferable so as to help alleviate suffering. No, I don’t feel dizzy. I have a feeling of true happiness. When we find something that really helps reduce the symptoms and disorders of a sufferer, first, it is a huge honor that we are allowed to experimentally apply these techniques until we discover how they work and how to better apply them, and second, it is the best reward for work that one can receive. That’s why we do it, basically. It not only fills you with very deep satisfaction when you realize that what you have dreamed of doing is possible, it also is very surprising to learn that things you never even caught a glimpse of are possible. In neurology and neuroscience, the field is moving so quickly that there is a whole mix of feelings.

As for the human soul, here we are entering the religious field. The question of whether there is a transcendental being we may call the soul is not physiology, it’s a question of metaphysics and personal religious belief.

A.P.:

In 2006 the neurologist Marcus E. Raichle published in Science an article titled “The Brain’s Dark Energy.”⁴

What do you think of what he said and that theory?

A.P.-L.:

It’s a huge problem. Let me give you some figures to give you an idea of the magnitude of the problem. The brain is approximately 2 percent of a human being’s weight. Nevertheless, it consumes 20 percent of the energy used by the human body. Shocking! Why does it need so much energy? The traditional answer is that we relate to the outside world through the brain. That’s no doubt true, but it’s not the main factor for explaining the huge energy consumption of the brain.

First, most of the energy consumed by the brain has nothing to do with information about the world that enters the brain through the senses but with what it wishes to inhibit. The brain consumes an enormous amount of energy-inhibiting information that enters through the senses. Obviously, this begs the question: Why does the brain allow so much information in. Why not filter it? We don’t know why, but it doesn’t filter it. It inhibits it later, and thus generates a reality. I mean, to see a tree, the brain doesn’t capture every leaf and branch and from each detail build up a tree. We don’t “see” the leaves and branches but this “new” tree created from the original tree.

However, even including that energy consumption used for inhibition, the brain needs only 1 to 2 percent of body energy for its relationship with the outside world. We still don’t know why the other 18 or 19 percent of the body’s entire energy consumption is dedicated to this organ. It’s more, much more, than your heart, liver, pancreas, or all of the other organs put together use. It’s a huge quantity. What’s it for? Marcus calls it the “dark energy” of the brain. Currently, one of the most influential hypotheses is that it has something to do with the self-reference effect, the concept of I, the conscience. But I don’t believe that. It may have something to do with it but if it does, it is by accident. From the evolutionary perspective, the brain is not like that. Chance made us self-aware, but the brain was designed to control and regulate the entire organism. I believe that that energy is “dark” only because we still don’t know for certain what the brain does with it, but things will change. We’ll find out what it is used for. I have the impression that the brain uses it for supporting a critical and fundamental role in organistically regulating the homeostasis of the individual’s organism, that is, health, in its widest sense.

A.P.:

The plasticity of the brain has become the holy grail of neuroscience. Is that true, or am I exaggerating?

A.P.-L.:

The nervous system is plastic, not in the sense that you can “plug in” the plasticity and use it but in the sense that it is changing constantly, and that change may develop into a benefit or harm to a specific individual. The real challenge is to sufficiently understand that plasticity in order to guide it, to increase certain changes and reduce others for the benefit of the individual at a given moment.

For a long time in my laboratory we have dedicated ourselves to the question of how to measure and guide the plastic capacity of the brain. That has produced very interesting results and we have learned a lot. Something of particular interest that has to do with what we were talking about before is that the brain is dedicated not only to its relationship with the external world but also to its internal world, to monitoring the internal organs of the body itself.

If when I relate to the external world my brain changes, does it change when it’s interacting with my insides, with my pancreas, for example? And if my pancreas changes because I have diabetes or pancreatitis, does this also change my brain? And if my brain changes, does this have an effect on my pancreas again? In the end, what this means is that the brain is healthier in a healthier body, but also, simultaneously, the body is healthier with a healthier brain. So the impact of the brain is two-directional and implies that if you maintain a full and flexible cognitive function throughout your life, you will be healthier. Or expressed another way: part of the reason why we end up having health problems beyond our control may have something to do with a loss of cerebral plasticity as time passes. So, perhaps plasticity really is the holy grail. At my center, we have been searching for it for years, and increasingly we are studying cerebral plasticity in relation to internal means, to the organismic relationship with the body and to the concept of whether cerebral health, in the sense of optimal cerebral function, translates into better control of overall health.

The challenge we face is to understand these relationships between brain and mind, on the one hand, and brain and the body on the other, so as to develop interventions that can modify, restore, or optimize the cerebral plasticity of each individual. We’ve been developing methods to measure in vivo the cerebral plastic capacity of humans. It‘s an enormous challenge because that has an effect on the well-being of each individual, of all humans. It has a lot to do with preventive action for everyone—for my father, for me, for my wife, for my kids—regardless of the disease being treated or prevented.

That’s the challenge we face, a challenge so huge that I see it as the main challenge for the rest of my academic life.

A.P.:

Wonderful. Thanks a lot, Alvaro.

A.P.-L.:

A pleasure, Adolfo.

24 Mind, Brain, and Behavior

Notes