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This might be a little dated now (a year or two), but I had a class with some emphasis on deep brain stimulation. The overall consensus from the professor was t

This might be a little dated now (a year or two), but I had a class with some emphasis on deep brain stimulation. The overall consensus from the professor was that we know that it does work, we know how the electronics and everything work, but we don't know what's happening in the brain to make it work. We don't know why we see the results we do with DBS, and they're sometimes pretty phenomenal results (like this tremor remover). Depression, chronic pain, tremors, and probably many things we don't know yet can be solved by putting some electrodes deep inside your brain and outputting a constant current. The one trouble spot is that the brain really, really does not like when foreign objects are embedded in it. The electrode goes in, punctures the blood brain barrier, and works for a while. When you put something foreign in the brain, astrocytes (brain cells that form the blood brain barrier) will form around the electrode and create a new blood brain barrier around it, causing the electrode that was once inside the brain to be on the outside. Also, the stimulation current seems to 'overdrive' the nearby neurons, causing them to die. This reduces the effectiveness of DBS, as living neurons are now farther away, reducing the effectiveness of the stimulation. Patients need to be awake during surgery so the doctors know when the electrode is placed correctly - https://www.youtube.com/watch?v=M_fjiEOb40M https://www.youtube.com/watch?v=M_fjiEOb40M

jlgreco 13y ago
> When you put something foreign in the brain, astrocytes (brain cells that form the blood brain barrier) will form around the electrode and create a new blood brain barrier around it, causing the electrode that was once inside the brain to be on the outside. Do the electrodes continue to work through this barrier? If they do, this formation seems like a good thing to me, unless there is something else going on.
- kghose 13y ago
  Yes, the current spreads regardless, since everything is basically saline (so to speak). So the more distant neurons are activated at a lower level (due to the r^2 drop in current density)
  - jlgreco 13y ago
    Have there been experiments with implanting numerous electrodes in a sort of shotgun pattern, but only activating the center ones at first so that when they "wear out" the outer electrodes can take over? That might mitigate the need to up the current or perform another surgery, but on the other hand I suppose you want to keep the number of electrodes in there to a minimum.
    - kghose 13y ago
      Well, that's a cool thought: current DBS leads do have multiple contacts. However, the main reason for this is that exact placement of the leads is not possible. Even with structural MRI and CT scans and so on, the placement is only approximate. So, surgeons have the patient awake and talking etc. to make sure they are not hitting the internal capsule (which would be bad for movement etc.) and then have access to multiple leads which they activate in turn to see which leads are best at mitigating symptoms (i.e. are activating/deactivating the appropriate structure) What I am very excited about is the concept of neurotrophic chemicals on electrode leads. These chemicals encourage neurons to grow processes towards them, thereby making a better and longer lasting connection with the electrode. If we ever get to a Neuromancer/Matrix like future where we 'jack in' our brains, I think neurotrophic electrodes with very fine spacing will be part of the technology, so that we can activate many neurons in many different patterns in a well controlled manner.
      - jlgreco 13y ago
        Aaah, very interesting. That is a much more elegant solution.
    - etrautmann 13y ago
      It's currently understood that it's the presence of the electrode that causes buildup of glial tissue, not the stimulation current, so this approach wouldn't really work. It isn't really necessary though, since you can turn up the current slightly to compensate for the buildup around the electrode. It's a relatively coarse manipulation, but we'll be increasingly using optogenetics as a replacement.
Florin_Andrei 13y ago
So, you have to use it wisely, as using it actually makes it less effective?
- kghose 13y ago
  That's an interesting thought. There is some push now to figure out if intermittent stimulation (rather than always on, as is commonly used now) works just as well. The main aim of this, however, is to make the batteries last longer.
kghose 13y ago
Very accurate summary! I would add * The current best guess is that the electrical stimulation inactivates the neurons (acting as a reversible lesion). Older surgeries used to do a real lesion near that brain region. * Parkinson's is, unfortunately, a progressive disease. So the decrease in efficacy of the stimulation is partly related to the fact that this disease itself is getting worse. We typically hear that DBS buys a patient about another decade (which is a lot).
- etrautmann 13y ago
  I'd be very surprised if electrical stimulation simply acts as local inhibition. This is inconsistent with other electrical stimulation experiments (eg: driving muscle movements by stimulating in M1), and would not provide the correct manipulation to the basal ganglia. The problem in Parkinson's is that the Substantia Nigra and a certain class of excitatory neurons start dying off, leading to less dopamine release. The electrical stimulation is thought to stimulate the remaining neurons to release additional dopamine to compensate for this loss.
  - refurb 13y ago
    Remember that the shaking you see in Parkinson's patients is not due to the disease, but that a side effect of the medication. Untreated Parkinson's patients "freeze".
  - kghose 13y ago
    Yes, this is not clear (as far as I know). The direct effect of inserting current pulses is to excite neurons. However, this is followed by a period of inhibition. I am not sure of the cellular mechanisms. A reasonable review (with full text) is found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2200868/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2200868/ The review details the suggestions that there are both excitatory and inhibitory effects of DBS. Another paper I know of is http://www.ncbi.nlm.nih.gov/pubmed/19864437 http://www.ncbi.nlm.nih.gov/pubmed/19864437 which goes into excitatory and inhibitory effects in cortex.
toomuchtodo 13y ago
Can we use transcranial magnetic stimulation as a substitute for deep brain stimulation? This would prevent that need to penetrate the skull, brain, etc.
- kghose 13y ago
  Hmm. I'm not well versed with this technique, but I believe the effect of TMS is restricted to cortex (the superficial parts of the brain). To affect deeper regions we would have to make the induced currents stronger, which would perhaps damage the cortex, and would certainly affect cortex as well as the deeper brain regions.
  - toomuchtodo 13y ago
    I.E. TMS requires more precision before being considered for this.
    - kghose 13y ago
      I'm not sure if it is precision. I think it is a fundamental limitation of the technique, since it involves inducing currents in the brain using a magnet located outside it. Another two interesting stimulation techniques are ultrasound and infrared. I was very, very surprised when I learned this, but infra red can penetrate skull and people are busy making stimulators using infrared.

jlgreco 13y ago

> When you put something foreign in the brain, astrocytes (brain cells that form the blood brain barrier) will form around the electrode and create a new blood brain barrier around it, causing the electrode that was once inside the brain to be on the outside. Do the electrodes continue to work through this barrier? If they do, this formation seems like a good thing to me, unless there is something else going on.

kghose 13y ago
Yes, the current spreads regardless, since everything is basically saline (so to speak). So the more distant neurons are activated at a lower level (due to the r^2 drop in current density)
- jlgreco 13y ago
  Have there been experiments with implanting numerous electrodes in a sort of shotgun pattern, but only activating the center ones at first so that when they "wear out" the outer electrodes can take over? That might mitigate the need to up the current or perform another surgery, but on the other hand I suppose you want to keep the number of electrodes in there to a minimum.
  - kghose 13y ago
    Well, that's a cool thought: current DBS leads do have multiple contacts. However, the main reason for this is that exact placement of the leads is not possible. Even with structural MRI and CT scans and so on, the placement is only approximate. So, surgeons have the patient awake and talking etc. to make sure they are not hitting the internal capsule (which would be bad for movement etc.) and then have access to multiple leads which they activate in turn to see which leads are best at mitigating symptoms (i.e. are activating/deactivating the appropriate structure) What I am very excited about is the concept of neurotrophic chemicals on electrode leads. These chemicals encourage neurons to grow processes towards them, thereby making a better and longer lasting connection with the electrode. If we ever get to a Neuromancer/Matrix like future where we 'jack in' our brains, I think neurotrophic electrodes with very fine spacing will be part of the technology, so that we can activate many neurons in many different patterns in a well controlled manner.
    - jlgreco 13y ago
      Aaah, very interesting. That is a much more elegant solution.
  - etrautmann 13y ago
    It's currently understood that it's the presence of the electrode that causes buildup of glial tissue, not the stimulation current, so this approach wouldn't really work. It isn't really necessary though, since you can turn up the current slightly to compensate for the buildup around the electrode. It's a relatively coarse manipulation, but we'll be increasingly using optogenetics as a replacement.

Florin_Andrei 13y ago

So, you have to use it wisely, as using it actually makes it less effective?

kghose 13y ago
That's an interesting thought. There is some push now to figure out if intermittent stimulation (rather than always on, as is commonly used now) works just as well. The main aim of this, however, is to make the batteries last longer.

kghose 13y ago

Very accurate summary! I would add * The current best guess is that the electrical stimulation inactivates the neurons (acting as a reversible lesion). Older surgeries used to do a real lesion near that brain region. * Parkinson's is, unfortunately, a progressive disease. So the decrease in efficacy of the stimulation is partly related to the fact that this disease itself is getting worse. We typically hear that DBS buys a patient about another decade (which is a lot).

etrautmann 13y ago
I'd be very surprised if electrical stimulation simply acts as local inhibition. This is inconsistent with other electrical stimulation experiments (eg: driving muscle movements by stimulating in M1), and would not provide the correct manipulation to the basal ganglia. The problem in Parkinson's is that the Substantia Nigra and a certain class of excitatory neurons start dying off, leading to less dopamine release. The electrical stimulation is thought to stimulate the remaining neurons to release additional dopamine to compensate for this loss.
- refurb 13y ago
  Remember that the shaking you see in Parkinson's patients is not due to the disease, but that a side effect of the medication. Untreated Parkinson's patients "freeze".
- kghose 13y ago
  Yes, this is not clear (as far as I know). The direct effect of inserting current pulses is to excite neurons. However, this is followed by a period of inhibition. I am not sure of the cellular mechanisms. A reasonable review (with full text) is found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2200868/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2200868/ The review details the suggestions that there are both excitatory and inhibitory effects of DBS. Another paper I know of is http://www.ncbi.nlm.nih.gov/pubmed/19864437 http://www.ncbi.nlm.nih.gov/pubmed/19864437 which goes into excitatory and inhibitory effects in cortex.

toomuchtodo 13y ago

Can we use transcranial magnetic stimulation as a substitute for deep brain stimulation? This would prevent that need to penetrate the skull, brain, etc.

kghose 13y ago
Hmm. I'm not well versed with this technique, but I believe the effect of TMS is restricted to cortex (the superficial parts of the brain). To affect deeper regions we would have to make the induced currents stronger, which would perhaps damage the cortex, and would certainly affect cortex as well as the deeper brain regions.
- toomuchtodo 13y ago
  I.E. TMS requires more precision before being considered for this.
  - kghose 13y ago
    I'm not sure if it is precision. I think it is a fundamental limitation of the technique, since it involves inducing currents in the brain using a magnet located outside it. Another two interesting stimulation techniques are ultrasound and infrared. I was very, very surprised when I learned this, but infra red can penetrate skull and people are busy making stimulators using infrared.