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Printable Handouts
Navigable Slide Index
- Introduction
- A short trip round the brain
- The usual scheme of the basal ganglia
- Human brain drawing
- Rat brain section
- Why 2 pathways from striatum
- An idea about the system
- Evidence that D2SPN’s are overactive
- Maybe STN is the problem
- Removing STN helps monkeys
- Removing STN is dangerous
- Deep brain stimulation of STN
- Stimulation does help but not via STN
- Human brain: looking for another target
- Human recordings support the change in target
- More support through intracellular recording in rats
- Optogenetics support a cortical action
- Freely moving rat experiments
- Evidence of cortical excitation
- Proof of antidromic activity
- More proof - timing is everything
- Explaining the effectiveness of cortical activation
- Striatal cell activity with and without dopamine
- D1 & D2 neurons are involved in increased activity
- 20 Hz rhythm after dopamine blockers
- Synchrony is toxic
- The theory in summary
- Acknowledgements
Topics Covered
- Deep Brain Stimulation has been a huge success for the relief of motor symptoms in Parkinson’s disease but no-one is sure how it works
- DBS was designed to resolve problems that fitted an out of date version of how the basal ganglia are changed by the disease
- This talk suggests an alternative, more modern, explanation of its effects.
Links
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Therapeutic Areas:
Talk Citation
Arbuthnott, G. (2014, June 2). Deep brain stimulation: a mysterious success or a clue to help localize the causes of Parkinsonism? [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 26, 2024, from https://doi.org/10.69645/LYSS7134.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Gordon Arbuthnott has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
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 Clinical Practice
Transcript
Please wait while the transcript is being prepared...
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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