“So we know that deep brain stimulation can be used in motor circuits to improve motor function,” Dr. Lozano commented. “And it looks like deep brain stimulation may be able to be used in mood circuits to control depression.”
Cognitive Function
In 2008, Dr. Lozano and colleagues published a report in which they had performed hypothalamic/fornix deep brain stimulation in a patient with morbid obesity. To their surprise, they found that the stimulation evoked detailed autobiographic memories in the patient.
Following up on that finding, the researchers conducted a pilot study in six patients with Alzheimer’s disease by implanting electrodes in the hypothalamus and fornix to see if they could improve memory. “We’re mapping out what areas of the brain become activated as a consequence of stimulating,” said Dr. Lozano. “By stimulating the hypothalamus, we are able to drive the circuit synaptically and transynaptically as one would expect based on the anatomical connections of the circuit.
“We know that there is a glucose utilization deficit, particularly in the temporal and parietal lobe in patients with Alzheimer’s disease, and by stimulating this area, one of our objectives is to see if we can reverse or reestablish glucose utilization,” he continued. “Although the brunt of the disease is in the hippocampus and the entorhinal cortex, the parietal lobe is relatively spared in Alzheimer’s disease. We think that it might still be open for business and open to stimulation, and we have some evidence now that we are able to activate this area…. We’re going to finish up our study in six patients with Alzheimer’s disease and hopefully report that soon. But so far, we know that it’s safe and it looks promising.”
In addition to inducing physiologic and neurocircuitry-related effects, deep brain stimulation can also produce major biologic effects, noted Dr. Lozano. “It turns out that we can use stimulation to make more neurons in the brain,” he said. “And this has been specifically done in rats…. If you take rats and you stimulate them in the fornix at the same settings that we use for our Alzheimer’s disease patients, we triple the number of new neurons…. So we think that it may be possible to use electricity not only to change the activity of neural circuits to drive circuits that are underperforming, to suppress pathologic activity in the brain, but it may also be possible to change the biology of circuits and maybe have enhanced repair and regeneration in the brain using electricity as the instrument to mediate that change.”
New Frontiers for Deep Brain Stimulation
“We’re going to see an expansion of indications for deep brain stimulation,” said Dr. Lozano. “By far, the greatest opportunity lies in psychiatric illness. There is much more psychiatry than neurology in our society. We have major disorders like depression and obsessive-compulsive disorder that are now being examined. There are multiple targets. In Parkinson’s disease, we have GPi, STN, and others. For the psychiatric illnesses, we also have multiple targets that we should consider. There are other [uses] of deep brain stimulation—for epilepsy, response to stimulation in minimally conscious states, [in combination with] gene therapy … cognitive dysfunction, and Alzheimer’s disease. So stay tuned. There is a lot more to come in this field.”
—Colby Stong