Deep brain stimulation: a mysterious success or a clue to help localize the causes of Parkinsonism?

Published on June 2, 2014   28 min

A selection of talks on Neurology

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0:00
Hello. This talk is about deep brain stimulation, a kind of surgical treatment for Parkinson's disease. My name's Gordon Arbuthnott. I worked most of my life in Edinburgh University in Scotland, but for the last six years, I lived and worked in the beautiful tropical island of Okinawa at the Okinawa Institute for Science and Technology Graduate University. I'm interested in this subject because of experiments I've done but mainly because I suspect this mysterious treatment is not fully understood, may actually hold an important clue about what actually goes wrong in Parkinson's disease.
0:42
This summary diagram lists the parts of brain that we think go wrong in Parkinson's disease. They represent the various parts of one of the motor systems of the brain. We start in the output layer of the cerebral cortex in layer five. We then go through several basal ganglia nuclei to the thalamus and eventually back to the cortex in layer one. This particular arrow was a big disappointment for me. We spent years tracing the connections from layer five through several basal ganglia nuclei and finally to thalamus and to cortex a few hundred microns from where we started four or five years earlier. But in the basal ganglia, the function is determined by dopamine. And of course dopamine is lost in Parkinson's disease. So it's in this big arrow that we have to find the causes of the symptoms of the disease.
1:38
Now we need to look in a bit more detail at that box that was called basal ganglia. In this diagram, we still have cortex and thalamus just as in the other one. And in between, the basal ganglia has been split up into several different boxes. It's on the striatum that most of the dopamine action happens. The striatal output cells, the SPN-- Striatal Projection Neurons-- are of two kinds, D1 and D2, marked by the kind of dopamine receptors that they make. The D1 cells project directly to the two output nuclei from the basal ganglia, which are marked here SNr and GPi. SNr is substantia nigra pars articulata. GPi is the internal segment of the globus pallidus. Those two output nuclei are also reached by the D2 projection cells. Only they have to go through the subthalamic nucleus-- that's STN in this diagram-- and/or GPe, the external part of the globus pallidus. Both of those then head off to the output nuclei. And incidentally, there's a hyperdirect pathway that goes straight from cortex to subthalamic nucleus. That one may well become more important later. This is the usual scheme of the basal ganglia. Anyone who's looked or listened to other talks about Parkinson's disease will have seen some similar version of this. But the brain's not made of boxes. Let's look at something more realistic.

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Deep brain stimulation: a mysterious success or a clue to help localize the causes of Parkinsonism?

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