BioEd Online

Electrodes implanted into the brain of a patient undergoing an experimental treatment for obesity have surprisingly improved his memory skills.

The startling and unexpected effects — reported in Annals of Neurology¹ — have prompted the Canadian team of neurologists to launch a new deep-brain stimulation (DBS) trial in patients with early Alzheimer’s disease. Three patients have already had electrodes implanted, says neurosurgeon Andres Lozano from the University of Toronto's Toronto Western Research Institute. “The surgery seems safe and the results are promising,” he says.

During DBS, a hair-thin electrode with four contact points is placed in a very precise area of the brain. Each contact can be stimulated individually with different frequencies of electric current — or switched off — by remote control. The tiny currents are intended to activate specific neural circuits in the brain that under-perform in particular disorders. The procedure is most often used to treat Parkinson’s disease but, in the past few years, neurosurgeons have been experimenting with treating psychiatric disorders including depression and obsessive-compulsive disorder.

The 50-year old patient described in the paper was the first to have DBS for obesity, in 2003. At around 190 kilograms his weight was life-threatening, and he had not responded to other forms of therapy. The surgeons chose to place the electrode in the hypothalamus, a small almond-sized area of the brain just above its base, because stimulating this area of the brain in animals can affect the amount of food they want to eat. In the past, neurosurgeons have tried to treat obesity by removing part of the hypothalamus.

Déjà vu

Lozano was surprised when the patient announced, during test brain stimulations in the operating theatre, that he was feeling a profound sense of déjà vu. The patient recalled what he considered to be a pleasant memory: a scene in a park with friends from about 30 years ago. The more intense the current, the more details of the scene he could fill in.

Prompting a memory from brain stimulation is not uncommon, but the researchers were intrigued that this happened from an electrode in the hypothalamus.

In a battery of neuropsychological tests performed before and after the surgery, the research team found that the patient's general mental performance remained basically unchanged. But his performance in complex memory tests involving interpreting and remembering pairs of words was dramatically improved when the electrodes were switched on. The tests were designed so that neither the patient nor the experimenter knew whether the brain was being stimulated during the test.

This specific type of memory improvement is thought to be linked to an area of the brain called the hippocampus. When the researchers looked at the patient’s brain using electroencephalography, they found that electric stimulation activated areas around the hippocampus. They team propose that the electrodes must inadvertently stimulate a bundle of neurons known as the fornix, which passes through the hypothalamus en route to the hippocampus.

Window into the brain

“The hypothalamus is a crowded place in terms of functions, with lots of things going on,” says Lozano. “That’s why we test the effect of stimulating each of the contact points in turn in the operating theatre — if something untoward happens, then we can just switch them off again.” But the unanticipated side-effect on memory is a positive one.

Although this is a only a single-patient study, Lozano says that the implications are very important. “For the first time we have a window into the neural circuitry of memory in humans — about which very little is known — that we can both access and modify.”

In March 2007 Lozano began a pilot study to investigate whether such stimulation could help to improve the failing memories of Alzheimer’s patients, before their disease is so far advanced that their neural circuits have been destroyed. If the procedure proves safe in six patients, he will start an larger international study to look at efficacy.

Unexpected discussion

“It is very exciting, and it has never been done before,” says Richard Henson, an expert on human memory at the University of Cambridge, UK. “It is one of those rare cases when it is necessary for medical reasons to stimulate the hypothalamus, and it is telling us something about the neural circuitry involved in learning.”

“It’s an interesting example of the sort of unexpected finding we may start to see as different brain areas are tested with DBS,” says Helen Mayberg, a neurologist at Emory University School of Medicine in Atlanta, Georgia. “It suggests that enhanced brain functioning — and not just reversal of abnormal behaviour — is possible with DBS, and that’s going to prompt a lot of discussion among scientists and ethicists.”

Whether the DBS procedure will prove helpful in obesity, as originally anticipated, is less clear. The patient does find his appetite is suppressed when the electrodes are switched on, but he has not lost weight as he tends to switch them off when he wants to eat.