Of the study of brain function

Since neurology and psychiatry evolved as independent medical disciplines in the 1960s, the level of understanding of the functions of, and diseases afflicting, the brain has increased manifold. One major development is the acceptance of the "connectionist model" (any brain function is activated by more than one part of the brain) as against the "modular model"(a function by any one part of the brain).

Another important development is the recognition of the dominance of the right hemisphere of the brain, which was for long thought to be a dormant or silent region. More important is the realisation of the link between the right hemisphere and the language function. This was earlier thought to be linked only to the left hemisphere.

A significant contribution to the "connectionist model" and to the understanding of the role of the right hemisphere in brain functions has been made by Dr. Michael R. Trimble, Professor of Behavioural Neurology, Institute of Neurology, London, who specialises in neuropsychiatry and behavioural neurology.

After completing his graduate studies in medicine in Birmingham, England, Prof. Trimble obtained a B.Sc. (Hons) degree in neuro anatomy, an M.Phil and an M.D. He is a Fellow of the Royal College of Physicians (RCP), London and a Fellow of the Royal College of Psychiatrists. Then he went to the Johns Hopkins Hospital, Baltimore, United States. The research unit that he heads at the Institute of Neurology in London specialises in neuropsychiatry and behavioural neurology. The main area of research in his unit relates to epilepsy, especially the effects of seizures on neural patterns in the brain, and the impact of epilepsy treatment on human behaviour. Dr. Trimble has published over 300 papers and authored six books. He has also edited 21 books on neuropsychiatry and behavioural neurology.

Dr. Trimble now works on the relationship between depression and literary creativity as also the dominant role played by the right hemisphere of the brain, which, he says, "is much more linguistic, more appreciative of music and melody." His research has revealed that the right hemisphere is involved in the emotional aspects of language, as also in metaphors, which are central to poetic expression.

Dr. Trimble was in Chennai recently to deliver the T.S. Srinivasan endowment lecture organised under the auspices of the T.S. Srinivasan Department of Clinical Neurology and Research (which provides comprehensive neurological care for patients from the lower middle class and middle class). Dr. Trimble spoke to Asha Krishnakumar on various aspects of brain functioning, diseases, drugs, and his research. Excerpts from the interview:

How do you define neuropsychiatry and behavioural neurology? Are they interdependent?

In the last century there were neither neurologists nor psychiatrists. There were only those who dealt with what are loosely called nervous diseases. This really meant diseases of the nervous system.

As the speciality of neurology developed, clinical skills also developed, and with this developed the skill of identifying lesions and abnormalities in the central nervous system. From this it gradually became clear, for example, that Parkinson's disease could be distinguished from multiple sclerosis. And this was aided by the development of psychiatry, particularly for patients who did not exhibit symptoms of neurological problems. So conditions such as multiple sclerosis and Parkinson's disease became identified with neurology. Various conditions that you could not find in patients when you examined them clinically became identified with psychiatry. So neurology became brain-orientated and psychiatry became psychology-orientated. Thus, the famous comment about the two specialities: "Neurology deals with a mindless brain and psychiatry, with a brainless mind."

By the 1960s you had neurologists who dealt only with brain problems, particularly of the nervous system. And psychiatrists dealt with what used to be called neurosis and psychosis.

But there were a number of patients who had many diseases but displayed only psychiatric problems. With new methods of investigation, these patients could be shown to have neurological problems. An example of a neurological problem with psychiatric symptoms would be epilepsy. You could also have patients with psychiatric problems, for example schizophrenia, but underlying the psychosis of schizophrenia you could find brain changes. The big revolution in this area was the advent of brain imaging.

When did this distinction between the two disciplines emerge? And what did it mean to the understanding of neurology?

This happened mainly in the 1960s and 1970s. And it has accelerated ideas (research) with regard to the way the brain functions. In the past, people very much thought in what I call the modular way. That is, that one part of the brain represents a certain function and that function is represented only in that part of the brain. But gradually people recognised what is called the connectionist view of how the brain works - that there are circuits within the many different brain sites that are involved in overall functions.

Do neurology and psychiatry overlap or are they interdependent?

Neurology and psychiatry are clearly related to each other. The brain is the seat of neural behaviour - all emotions, all passions, hallucinations and delusions and speech and so on. So, clearly, there cannot be psychiatric symptoms without a brain representation. But much of traditional neurology has ignored some important aspects of the brain function. The brain has four lobes. By far the largest are the frontal lobes. For many years the frontal lobes were called the silent area of the brain. People thought they did nothing. Neurological symptoms, such as the loss of the use of an arm, sensory disturbances in the arm or leg and even speech disturbances, were largely related to lesions in the parietal and occipital regions on which traditional neurology concentrated. But it has become quite clear that many of our most important social functions are linked to the frontal lobes. It is now called the region of the brain related to executive functions. It acts as a sort of central control. It not only knows what is going on in the brain but reports back and decides about what should happen next.

Many psychiatric symptoms have to do with the frontal and temporal lobes. So if you stimulate the temporal lobes you probably hallucinate and if you damage it you get memory disturbance or amnesia. If you damage the frontal lobes, you will lose your ability to plan your activities effectively. Central lobe damage will lead to inappropriate social behaviour.

Now, what happened to the other side of psychiatry? Sigmund Freud, whom most people identify as the founder of modern psychiatry, was a neurologist, extremely capable and able. But he was not a psychiatrist. He developed a new psychology - one which goes with psychiatric illness and a psychological treatment that you employ for people with stress-related disorders, which people with disorders such as schizophrenia are susceptible to.

What has tended to happen is that even with a biological approach to the treatment of patients, which alters neural transmitters with chemicals to regulate brain functions, overriding importance has been given to the role of management. This development occurred in the 1970s, and certainly now in the 1990s, when we have a lot of new, powerful, specialised drugs which offer considerable hope, particularly for severe psychiatric and neurological illnesses.

But do these specialised drugs not also have side-effects?

Yes, most drugs are dirty as they have multiple action. And the intent in neuro-psycho-pharmacology has been not to eliminate side-effects but to enhance the therapeutic effects. This does not always work. For example, a breakthrough drug in treating schizophrenia was found to block dopamine receptor, a major transmitter in the brain. If you impair brain dopamine you end up with a disease similar to Parkinson's disease. And to treat Parkinson's disease you give Eldopa, which could lead to the patient developing psychosis, which in some cases is like schizophrenia. Most traditional drugs have this kind of a problem.

In the last few years, drugs have been developed, which have fewer side-effects but still are anti-psychotic. So, there is a tendency to refine the old-fashioned medication. But the old-fashioned medication is still important, particularly in a country like India, as it is considerably cheaper and still effective.

So far only the left hemisphere of the brain has been emphasised. Why is it that now a lot of importance is being given to the right hemisphere?

In the European tradition, which is, of course, the Christian tradition - maybe in your tradition too - God could not be seen to be creating anything asymmetrical. So the brain was considered symmetrical. The right and the left sides of the brain had to be equal. Then, Brola, an anthropologist and neurologist, found patients with left-side brain lesions who could not speak. And, then, gradually it became clear that the left side of the brain regulated speech.

It was also found that there is some link between the dominance of the right side of the body (which is controlled by the left side of the brain) and language function. As it is easy to test language skills, this testing became part of clinical practice, as also paying attention to the left hemisphere of the brain. Difficulties with regard to writing, reading and speaking, which are functions of the left hemisphere, were investigated thoroughly.

The right hemisphere was thought of as non-dominant. There was a failure to appreciate that the right hemisphere had considerable language ability.

Now people are into two things: first, to examine the functions of the right hemisphere by brain-imaging techniques. This has shown that the right hemisphere is activated in normal speech as well as in certain specific situations which had to do more with figurative rather than literal aspects of speech.

That it is clinically important to understand the right brain is a different issue; more important is to understand how the brain works in relationship to human activity as a whole. As I mentioned, the right hemisphere is much more linguistic, more appreciative of melody and music. So, some people have tried music therapy for those who have had a stroke of the left hemisphere.

Through musical intonation maybe you could regenerate some speech in aphasic (speech impairment) patients. This has been tried with some success. It is called music therapy. So, if the left side of the brain is damaged and the right side is not, then we work on the right side by tapping into such musical potential.

In your T.S. Srinivasan endowment lecture you spoke about the association between depression and literary creativity. Can you give an account of the various hypotheses about this association? Why is this association stronger in patients who specialise in the arts rather than in the sciences?

I was looking at associations between the brain and literary creativity. It became clear to me that people who write good prose, on the whole, do not write good poetry. And people who write good poetry, on the whole, do not write good prose. Then I started looking at the distinctions between the two.

The first conclusion I came to was that poetry is a different way of expression. I tried to find out the disease associations of poetry. There is considerable literature that suggests that manic depressive illness is associated with poetry; not with the visual arts, not with being a scientist or a politician.

Now what does this mean? Not that all poets are manic depressives, nor that all manic depressives are poets. I am only using manic depressive illness to understand which part of the brain may be linked more to poetry, in the same way that aphasia is a link between the left side of the brain and the faculty of speech.

And, it just so happens that manic depressive illness is over-represented in poets. To me this means that if you can get to the neurology of manic depressive illness, that is, what brain lesions occur, there can be clues to the link between manic depressive illness and poetry.

If you damage the right side of the brain in some way then it leads to mania. If you damage the right hemisphere you lose the ability to speak with musical rhythms, tones and expressions.

First, it is clear that the right side is associated with poetry and music. Second, by implication, the right side is related to manic depressive illness. When people become manic they often become more musical in their speech and rhyme and repeat as poets do. So there are some links between the manic depressive's language and a poet's.

Is there any study on the evolution of language? Does it have anything to do with the importance given to the right hemisphere of the brain so far?

Anthropologists have written about it. Language must have evolved for emotional purposes - to warn people, to bring groups together, to bind them. The early languages were musical and much of the early transmission of text was in the form of oral tradition.

As our culture became dominated by writing and reading, and now by television and so on, maybe we are retreating from the specific development of the right hemisphere and also from the enjoyment of poetry. With the development of television and radio, we have virtually forgotten poetry.

How does brain imaging work?

You can give somebody an injection of a radioactive material, take a picture of the radioactivity of the brain, wait a few moments and then do exactly the same again. But the second time, have the person doing something like reciting a poem. Then, by comparing one image with the other, you can highlight those parts of the brain that are related to certain activities. That is how people have been identifying the distributive circuits within the brain.

The new imaging techniques based on magnetism and magnetic resonance are really leading to fantastic advances in looking at the brain and its functioning. These techniques will also become much cheaper over time and much more widely available, even for countries such as India.

What are the issues at the frontier of research in the field of neuropsychiatry?

The two main issues of research are: what is going on in the brains of patients with depression, schizophrenia, epilepsy and so on. And this is being unravelled, mainly with the brain imaging techniques. The other question is, what is the chemistry of these conditions.

One grey area we are trying to understand is what it means to have a lesion in one part of the brain for the neurotransmitters to regulate behaviour. This now takes you to altering the neurotransmitters to try to equip the brain into better order. So, that is why research on neurotransmitters is being done now.

People are looking at alterations. How do you put back into order a neurotransmitter system which is out of order? The most interesting example in the last few years has been the development of alteration for dementia and Alzheimer's disease.

The major issue of research at present is neurochemistry and the development in treating Alzheimer's disease and the related dementia.

Have developments in pharmacology kept pace with research in neuropsychiatry? Is there any research on to reduce the side-effects of the drugs used on neuro-psychiatric patients?

There are hundreds of neurotransmitters being developed. But the development of drugs is limited.

But I think there is great hope for the future. The development of better psychopharmacological and neurological drugs and the knowhow, as far as I can see, is going to come from targeting the drugs. For the moment, we take a drug by mouth-first, it goes all over the body - your heart, lungs and so on - and so you get side-effects all over your body, and second, it goes all over your brain.

Now, the idea of targeting a drug is that it goes nowhere else. But, then, the selector is in the brain. This is going to be the way of the future. This may initially mean surgically implanting substances in specific parts of the brain. This is the kind of things drug companies generally are looking at, which may reduce side-effects and increase therapeutic effects.