Deep brain stimulation evokes long-lost memories

Canadian surgeons have made a serendipitous discovery. While using deep brain stimulation to try suppressing the appetite of a morbidly obese patient, they inadvertently evoked in the patient vivid autobiographical memories of an event that had taken place more than 30 years previously. They also found that the electrical stimulation improved the patient's performance on associative memory tasks.

These unexpected findings raise the possibility that deep brain stimulation could be used to treat patients with Alzheimer's Disease, and the research team is now beginning a small clinical trial involving 6 patients who have been diagnosed with that condition.

Deep brain stimulation (DBS) is an invasive technique involving the implantation of an array of electrodes into the brain. The implant, which is usually attached by thin wires to a small battery which is itself implanted under the skin near the collarbone, acts as a " brain pacemaker" - it emits regular electrical pulses, which activate or inhibit specific regions of the brain.

DBS began as an experimental surgical technique about 10 years ago, but has since been used quite widely- and often successfully - to treat a various conditions. Following FDA approval in 2003, for example, the technique has been used to treat more than 30,000 patients with Parkinson's Disease (see this film clip); more recently, it has been used to treat depression and Tourette's Syndrome, and has even improved brain function in a patient in the minimally conscious state.

The patient in the current study question is a 50 year-old man who weighs 190kg; he had refused a gastric bypass and did not respond to numerous other treatments, including dietary regimes and medication. He was subsequently referred to a team of neurosurgeons, who later implanted electrodes into a nucleus in the ventral hypothalamus.

The hypothalamus controls the release of hormones, and is also involved in various metabolic functions. It is also known to contain a satiety centre, and surgeons have in the past treated obesity by lesioning the ventral nucleus. In this case, DBS was preferred over a hypothalamic lesion, because it is reversible. The surgical team, led by Andreas Lozano, a professor of neurosurgery at the University of Toronto and Toronto Western Hospital, report their findings in the Annals of Neurology:

Unexpectedly, the patient reported sudden sensations that he described as "deja vu"...the perception of being in a park with friends, a familiar scene to him. He felt he was younger, around 30 years old. He recognized his epoch-appropriate girlfriend among the people. He did not see himself in the scene, but instead was an. The scene was in color; people were wearing identifiable clothes and were talking, but he could not decipher what they were saying. As the stimulation intensity was increased from 3.0 to 5.0 volts, he reported that the details in the scene became more vivid.

Equally remarkable was the effect of hypothalamic stimulation on the patient's performance on a standardized neuropsychological assessment and various memory tests. After 3 weeks of DBS, the patient performed significantly better on verbal learning and spatial associative memory tasks, as compared with before the surgery. His IQ score also apparently increased by 9 points following the treatment.

These effects were attributed directly to the electrodes embedded in his brain. In a double-blind experiment performed 3 weeks after implantation, the patient's scores on all the tasks returned to pre-operative levels when the electrodes were switched off, but improved again when they were switched back on.

The hypothalamus is not normally associated with memory, and the researchers believe that what they had observed was due to an adjacent and connected structure called the fornix. This is a component of the limbic system, a network of structures which includes the hippocampus and amygdala, and which is known to be involved in memory and emotion. Brain imaging confirmed that stimulation confirmed that stimulation of the hypothalamus led to increased activity in the hippocampus and other medial temporal lobe structures (see image at the top).

Now that it is known to alter memory function, electrical stimulation could be used by researchers to gain a better understanding of the substrates of memory in humans. And, because of the significant improvement in memory tasks demonstrated by this patient, Lozano and his colleagues have started a small clinical trial, in which 6 Alzheimer's patients will be treated with DBS. 3 of these have already had electrodes implanted into the hypothalamus, but it is still unclear if the findings of this study can be reproduced.

Reference:

Hamani, C. et al (2008). Memory enhancement induced by hypothalamic/fornix deep brain stimulation. Ann. Neurol. 63: 119-123. [Abstract]