Andres Lozano: Parkinson’s, Depression and the Switch That Might Turn Them Off (Transcript)

We’re able to drive down area 25, down to a more normal level, and we’re able to turn back online the frontal lobes of the brain, and indeed we’re seeing very striking results in these patients with severe depression.

So now we are in clinical trials, and are in Phase III clinical trials, and this may become a new procedure, if it’s safe and we find that it’s effective, to treat patients with severe depression. I’ve shown you that we can use deep brain stimulation to treat the motor system in cases of Parkinson’s disease and dystonia.

I’ve shown you that we can use it to treat a mood circuit in cases of depression.

Can we use deep brain stimulation to make you smarter? Anybody interested in that? Of course we can, right?

So what we’ve decided to do is we’re going to try to turbocharge the memory circuits in the brain. We’re going to place electrodes within the circuits that regulate your memory and cognitive function to see if we can turn up their activity.

Now we’re not going to do this in normal people. We’re going to do this in people that have cognitive deficits, and we’ve chosen to treat patients with Alzheimer’s disease who have cognitive and memory deficits. As you know, this is the main symptom of early onset Alzheimer’s disease.

So we’ve placed electrodes within this circuit in an area of the brain called the fornix, which is the highway in and out of this memory circuit, with the idea to see if we can turn on this memory circuit, and whether that can, in turn, help these patients with Alzheimer’s disease.

Now it turns out that in Alzheimer’s disease, there’s a huge deficit in glucose utilization in the brain. The brain is a bit of a hog when it comes to using glucose. It uses 20% of all your — even though it only weighs 2% — it uses 10 times more glucose than it should based on its weight. Twenty percent of all the glucose in your body is used by the brain, and as you go from being normal to having mild cognitive impairment, which is a precursor for Alzheimer’s, all the way to Alzheimer’s disease, then there are areas of the brain that stop using glucose. They shut down. They turn off.

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And indeed, what we see is that these areas in red around the outside ribbon of the brain are progressively getting more and more blue until they shut down completely. This is analogous to having a power failure in an area of the brain, a regional power failure. So the lights are out in parts of the brain in patients with Alzheimer’s disease, and the question is, are the lights out forever, or can we turn the lights back on?

Can we get those areas of the brain to use glucose once again? So this is what we did. We implanted electrodes in the fornix of patients with Alzheimer’s disease, we turned it on, and we looked at what happens to glucose use in the brain. And indeed, at the top, you’ll see before the surgery, the areas in blue are the areas that use less glucose than normal, predominantly the parietal and temporal lobes.

These areas of the brain are shut down. The lights are out in these areas of the brain. We then put in the DBS electrodes and we wait for a month or a year, and the areas in red represent the areas where we increase glucose utilization. And indeed, we are able to get these areas of the brain that were not using glucose to use glucose once again.

So the message here is that, in Alzheimer’s disease, the lights are out, but there is someone home, and we’re able to turn the power back on to these areas of the brain, and as we do so, we expect that their functions will return. So this is now in clinical trials. We are going to operate on 50 patients with early Alzheimer’s disease to see whether this is safe and effective, whether we can improve their neurologic function.

So the message I want to leave you with today is that, indeed, there are several circuits in the brain that are malfunctioning across various disease states, whether we’re talking about Parkinson’s disease, depression, schizophrenia, Alzheimer’s. We are now learning to understand what are the circuits, what are the areas of the brain that are responsible for the clinical signs and the symptoms of those diseases.

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We can now reach those circuits. We can introduce electrodes within those circuits. We can graduate the activity of those circuits. We can turn them down if they are overactive, if they’re causing trouble, trouble that is felt throughout the brain, or we can turn them up if they are underperforming, and in so doing, we think that we may be able to help the overall function of the brain.

The implications of this, of course, is that we may be able to modify the symptoms of the disease, but I haven’t told you but there’s also some evidence that we might be able to help the repair of damaged areas of the brain using electricity, and this is something for the future, to see if, indeed, we not only change the activity but also some of the reparative functions of the brain can be harvested.

So I envision that we’re going to see a great expansion of indications of this technique. We’re going to see electrodes being placed for many disorders of the brain. One of the most exciting things about this is that, indeed, it involves multidisciplinary work. It involves the work of engineers, of imaging scientists, of basic scientists, of neurologists, psychiatrists, neurosurgeons, and certainly at the interface of these multiple disciplines that there’s the excitement.

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