Repetitive Transcranial Magnetic Stimulation Update

Jonah posted an href="http://scienceblogs.com/cortex/2008/05/tms.php">interesting
video of  href="http://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation"
rel="tag">Transcranial Magnetic Stimulation (TMS)
on The Frontal Cortex.  That got me to
wondering if there was anything new.  



In January 2007, the US FDA href="http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4273b1_00-index.htm">concluded
that rTMS was safe, but they were unconvinced of its effectiveness.
 Their conclusion href="http://www.spectrum.ieee.org/jan07/comments/1697">was
arguable,
but the arguments fell short.  For one thing, the initial
application compared rTMS to ECT.  It was safer, but less
effective.  Also, another study compared rTMS to sham
treatments.  The stats showed it was statistically effective,
but the p-value was 0.057.  It had to be 0.050, or less, to be
convincing.



TMS, by the way, is a way of manipulating brain function.  It
can be used for href="http://scienceblogs.com/developingintelligence/2008/01/magnet_to_the_head_tmss_effect.php">research.
 It also can be used clinically, especially if done
repetitively in the same area (rTMS).  It is being
investigated for use in treatment of href="http://www.ncbi.nlm.nih.gov/pubmed/12377400">depression,
href="http://scienceblogs.com/retrospectacle/2006/06/brain_ray_gun_cures_migraines.php">migraine,
href="http://scienceblogs.com/corpuscallosum/2007/01/transcranial_direct_current_st.php">fibromyalgia,
href="http://www.ei-resource.org/news/autism-news/autism-helped-by-transcranial-magnetic-stimulation/"
rel="tag">autism, and other conditions.



One limitation is that the devices generally used can't stimulate brain
that it deeper than about 1-2 centimeters into the cortex.
 Now, there is a company called Brainsway that has developed a
device that can penetrate 5-6 cm in a clinically useful fashion.
 

Of course, it has been possible to generate deep magnetic fields for a
long time.  Just use more power.  The problem is that
the brute-force approach increases the risk of tissue damage, or of
nasty adverse events, such as seizures.  The Brainsway device
uses multiple small coils.  These produce fields that overlap.
 It is possible to position them so that the greatest overlap
occurs in the area where the stimulation is desired.



This is explained in a recent article in the MIT magazine, Technology
Review.  

href="http://www.technologyreview.com/Biotech/20789/">

href="http://www.technologyreview.com/Biotech/20789/">A
Gentler Way to Jump-Start the Brain

By Jennifer Chu

May 19, 2008



...In order to reach deeper regions, researchers would have to increase
the intensity of the electric current flowing through the coil, which
could induce painful side effects such as seizures and tissue damage.



Instead, Abraham Zangen, one of two inventors of Brainsway's deep TMS
approach, and his colleagues designed a new coil configuration that is
able to excite neurons at a depth of four centimeters, using the same
intensity of current used in standard TMS coils. Instead of a single
coil generating a single magnetic field through the brain, Zangen has
outfitted a helmet with a number of small coils, each producing a
separate magnetic field. As researchers run a standard current through
the helmet, the coils, which are connected in a series, produce
multiple fields that add up, generating a much stronger magnetic field
that goes deeper into the brain before dropping off...

They had good reults in a preliminary study with 50 persons with
treatment-refractory depression.  Perhaps more interesting, is
the potential to broaden the clinical applications:

Meanwhile, Brainsway is designing different coils to
tackle brain regions associated with other conditions, such as
post-traumatic stress disorder, autism, and drug addiction. Zangen says
that in addition to stimulating underactive areas of the brain such as
those associated with depression, deep TMS can be used to inhibit brain
regions that may be abnormally overactive, such as during addiction.

A quick fix for addiction?  Probably not.  But if
they could reduce or eliminate drug craving, that would be a useful
adjunct to traditional abstinence-based treatments.  



On the other hand, if it is possible to treat
addiction, it might also be possible to cause
addiction.  That is a bit of a disturbing notion.
 (In fact, it was href="http://en.wikipedia.org/wiki/Tasp">anticipated
by the science-fiction author Larry Niven.)



But we already have plenty of things that cause addiction, so I don't
think this would change the world, really.



As for the treatment of mood disorders, the folks at Brainsway think
that their device will be better than regular rTMS, because it can
penetrate deep enough to reach the href="http://en.wikipedia.org/wiki/Limbic_system">limbic
system.  This has led them to posit a hypothesis:

href="http://www.israel21c.org/bin/en.jsp?enZone=Health&enDisplay=view&enPage=BlankPage&enDispWhat=object&enDispWho=Articles%5El1233">

href="http://www.israel21c.org/bin/en.jsp?enZone=Health&enDisplay=view&enPage=BlankPage&enDispWhat=object&enDispWho=Articles%5El1233">Israel's
Brainsway stimulates a magnetic remedy for depression

By Nicky Blackburn  

February 19, 2006



...The magnetic coil, which is placed on specific areas of the
patient's scalp, sends strong directed magnetic pulses through the
brain to stimulate the Nucleus Accumbens (the part of the brain
responsible for positive stimuli) and the neurons connected to it. "By
repeated artificial stimulation of electrical activity created by the
coil, we boost the sensitivity of these circuits so they will work more
efficiently," says Dr. Hilik Lewkovitch, at Brainsway.



The result is that the next time natural stimulation occurs, such as
something pleasant that the brain responds to, the patient will respond
more strongly, enjoy it more, and seek to repeat the experience. By
intensifying sensitivity this causes the patient to respond normally to
the environment...

This hypothesis strikes me as dreadfully simplistic, so I am skeptical
of its value.  With the human brain, as complex as it is, most
initial hypotheses are false.  But you have to start somewhere.



The FDA still has to figure out how they are going to evaluate the
treatment.  It is a novel treatment, so companies that try to
get approval from the FDA have to do some guesswork to try to
anticipate what will be needed.  That is unfortunate, but
true.  



Despite the bureaucratic hurdles, the Brainsway approach sounds
promising.  Perhaps they will be able to get that magic
p-value of 0.050.