'When we turn the current on, the patients report the emptin

http://www.guardian.co.uk/science/story/0„1743846,00.html

‘When we turn the current on, the patients report the emptiness suddenly disappears’

· Operation offers hope to the previously untreatable
· Hair-thin electrodes used to stimulate parts of brain

Alok Jha, science correspondent
Friday March 31, 2006
The Guardian

Sufferers from depression who do not respond to existing treatments could soon benefit from a new procedure in which electrodes are inserted into the core of the brain and used to alter the patient’s mood.
Later this year, scientists at Bristol University will conduct the first trials of the so-called deep brain stimulation method on sufferers from depression. They will use hair-thin electrodes to stimulate two different parts of the brains of eight patients who suffer from an extreme form of recurrent unipolar depression - where mood only swings in one direction.

If the trials are successful, deep brain stimulation could be extended to the estimated 50,000 people in the UK who suffer from depression but cannot be helped by drugs or electroconvulsive therapy.

“There are thousands of people in this country who have depression who are not responding, who are disabled by it,” said Andrea Malizia, a consultant senior lecturer at Bristol University’s psychopharmacology unit. He will lead the experiments with David Nutt, head of Bristol’s psychopharmacology research unit, and Nik Patel, a surgeon at the nearby Frenchay hospital.

Deep brain stimulation is already used to treat people suffering from Parkinson’s disease, a neurodegenerative disorder that results in uncontrollable tremors and affects mobility. Thousands of people worldwide have benefited from the surgery, which involves implanting the electrodes several centimetres into the brain. Brain scans are used to pinpoint which parts of the brain are acting incorrectly, and the electrodes then interfere with the electrical activity there, blocking the signals and easing the symptoms.

Currently, last-resort measures to help people with intractable depression have included cutting out or lesioning parts of the brain. Deep brain stimulation would largely give the same results, without the need for such drastic surgery.

Preliminary research by neuroscientists in Canada and the Netherlands has already suggested that the treatment could prove effective. Last year, Helen Mayberg, a neurologist at Emory University’s school of medicine in Atlanta, published the results of a decade of research which pinpointed a 2.5cm-wide part of the brain called the subgenual cingulate region (SCR) as playing a major role in dealing with affective information. The SCR is the lowest part of a deep band of tissue running along the central part of the brain. Dr Mayberg had noticed that this region was overactive in depressed people and that its activity correlated with their changing symptoms. When they were treated with antidepressant drugs, the activity went down.

By inserting electrodes into the brain while the patient is conscious (so that the surgeon knows if they have hit the right spot), Dr Mayberg found remarkable results. When she published her work, she said: “In the operating room, when we first turn the current on and get into the right location, the patients report that the heaviness or emptiness suddenly disappears. If they had a sense of a black cloud, they report it physically lifting.”

The moment the electrodes were turned off, some of the positive effects vanished, but the overall results - four out of six patients were lifted from depression for six months - were encouraging.

The Bristol trials will, in addition, target an area of the brain called the ventral anterior capsule, identified as playing a role in determining mood by a research team in Utrecht. “This connects the orbito-frontal cortex - which is more related to emotion, assessing of certain situations - to the thalamus, which is the big relay station of the brain,” Dr Malizia said. This part of the brain has already been targeted for conditions such as obsessive compulsive disorder, but researchers noticed that stimulating this area also affected the mood of most of their patients.

Because of the preliminary results from both areas of the brain, Dr Malizia’s team will aim to stimulate both. “The reason is that neither have a 100% success rate,” he said.

Identifying suitable volunteers for the trial will be crucial. “It can either be people referring themselves or health professionals referring them,” said Dr Malizia. “They must have good medical information from the past and they must be anchored to a local clinical service that will carry on looking after them.”

The experiments will answer several questions, not least how long each part of the brain needs to be stimulated for the treatment to work, in which order the parts are best stimulated and for how long the treatment should be used. The first results will be available within a year of the trials.

If the technique is successful, there is no theoretical reason why it could not be adapted to improve memory or treat addiction, which some scientists see as a form of retained long-term memory.

“The answer to the generic question has to be that it is possible for a variety of conditions. Where things become difficult is specifics,” said Dr Malizia. For something like Parkinson’s disease, deep brain stimulation works because there is solid scientific evidence showing which parts of the brain are responsible and, therefore, can be usefully targeted.

But Dr Malizia does not rule out the possibilities, arguing that whatever technology there is, people are bound to use it if it works, for example if, in 30 years or so, someone can improve memory by deep brain stimulation.

“I never cease to be surprised by what not only people but what society finds tolerable and desirable,” he said. “Would you have thought 100 years ago that people would go around having things injected in to their lips and breasts and bits cut out of their skin?”

Footnotes

Recurrent unipolar depression A state of melancholia that has become disruptive to people’s lives. Being in a sad mood is colloquially referred to as being depressed but clinical depression goes much further and symptoms can last two weeks or longer.

Deep brain stimulation A technique used to disrupt the brain’s electrical activity, thereby changing behaviour. Thin electrodes are inserted into the brain at a specific point and the electrical signals present there either boosted or blocked, depending on the condition being treated.

Subgenual cingulate region The lowest part of a deep band of tissue running along the central part of the brain. It has a vital role in modulating our negative moods.

Ventral anterior capsule A region of the brain that connects the frontal cortex, which deals with emotion, to the thalamus, which processes information from the senses and transmits it to the other parts of the brain.