Towards human circuit analysis, for clinical benefit?

This article in the latest issue of the Journal of Neuroscience is interesting in the sense that they are do human brain stimulation of the hypothalamus, for the treatment of cluster headaches – but they then do positron emission tomography (PET) to examine the downstream neural circuits responsible for the abolition of the perception of headache.

Hypothalamic Deep Brain Stimulation in Positron Emission Tomography

This moves the field of brain stimulation from simple stimulate-and-see-what-happens, towards more of a study of human neural circuitry and how stimulation drives activity in connected locations. It’s possible this will lead, in the future, to better and more focal stimulation protocols, as people figure out what the “circuit-level” phenomena are that correct particular aspects of neural dysfunction. Perhaps someday we will have a map of the “hot spots” where stimulation of a small chunk of matter can modulate a wide degree of neural circuitry for the better.

(Last year, Helen Mayberg and colleagues’ deep-brain-stimulation-and-depression paper got at this issue as well, in which they stimulate the cingulate and (perhaps surprisingly) sent depressed patients into remission, and furthermore changed the activity of frontal structures from the abnormal state, back to a more normal pattern of activity.)

These studies are perhaps setting a good precedent for brain-stimulating neuroclinicians to follow.

Ed

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5 thoughts on “Towards human circuit analysis, for clinical benefit?

  1. The brain-stimulation-for-depression-thing most certainly has my attention, though if one stands back and thinks about it, it seems to be a more focused version of ECT (shock therapy) which shows a similar success profile for TR Depression. The vagus nerve stuff is pretty neat, too. Unfortunately, I think the public has been pretty stigmatized by the frontal lobotomy fiasco of the 20th century, and rightly so, so psychosurgery is going to have an uphill battle to win the hearts and minds of the average joe and jane.

    Nice post.

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  2. Hi

    Excellent post on a growing field. You hit the nail on the head when you talk about identifying the circuitry. Much of the fMRI identifies local hot spots of cognitive activity but not so much about the integrated circuitry of behaviour etc.

    You cite the Mayberg ‘s et al paper as an example of brain stimulation. This was a very small study and in reality only two of the six really got good recoveries from the stimulation. Two did OK and two did not. Our ability to generalise from this is limited although just out in the AJP is a brief paper indicating the ability to predict who will respond to psychotherapy based on the activity level of the cingulate gyrus.

    see
    http://gandalwaven.typepad.com/psychology_and_the_singul/2006/04/brain_scans_pre.html

    I suspect what we will begin to see is not single focussed situation but multiple focussed stimulation of different points either in parallel or serially. It just get better and better.

    Regards
    Chris Allan
    http://gandalwaven.typepad.com/psychology_and_the_singul/

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  3. Just to develop on this. One of the exciting thing about actual brain stimulation is to allow the devleopment of testable hypotheses about brain circuitry. This allows to predict outcomes and then test them out it a much more controlled way.

    Chris

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  4. I don’t know if this post was triggered by today’s NYT Magazine article on DBS to treat “untreatable depression”. Mayberg is interviewed in the article, which focuses on stimulation of area 25 as a network foci for depression.

    Also, I like the long-range thinking of how neuromedicine improvments mimic neuroscience improvements, i.e. how focal, low-voltage DBS of Area 25 is like a more targeted form of electroconvulsive shock theraphy (100V over the whole brain). What’s the next step? Targeting specific cells?

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  5. > Just to develop on this. One of the exciting thing about
    > actual brain stimulation is to allow the devleopment of
    > testable hypotheses about brain circuitry. This allows to
    > predict outcomes and then test them out it a much more
    > controlled way.

    Absolutely. Especially, noninvasive methods of stimulation could be very useful as screening methods for deep stimulation methods. For example, transcranial magnetic sitmulation (TMS), which can be done presurgically, could be useful in principle for screening many candidate sites for stimulation using more enduring methods (deep brain stimulation with implanted, low-voltage electrodes). This could open a whole new field of interventional brain stimulation.

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