The Corpus Callosum

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Objective diagnosis is in some
ways the holy grail of medicine.  It has been maddeningly elusive
in psychiatry.  Now comes a paper in which the authors suggest
that they may have found this treasure.

The paper details a method of using magnetoencephalography to assess
human brain function.  They claim that, in a select population, it
can correctly identify patients with PTSD with 90% accuracy. 

href="http://www.iop.org/EJ/abstract/1741-2552/7/1/016011/">The
synchronous neural interactions test as a functional neuromarker for
post-traumatic  stress disorder (PTSD): a robust classification
method based on the bootstrap
A P Georgopoulos et
al
2010 J. Neural Eng. class="cite_volume">7 016011


Abstract. Traumatic experiences can produce
post-traumatic stress disorder (PTSD) which is a debilitating condition
and for which no biomarker currently exists (Institute of Medicine (US)
2006 Posttraumatic Stress Disorder: Diagnosis and Assessment
(Washington, DC: National Academies)). Here we show that the
synchronous neural interactions (SNI) test which assesses the
functional interactions among neural populations derived from
magnetoencephalographic (MEG) recordings (Georgopoulos A P et al 2007
J. Neural Eng. 4 349-55) can successfully differentiate PTSD patients
from healthy control subjects. Externally cross-validated,
bootstrap-based analyses yielded >90% overall accuracy of
classification. In addition, all but one of 18 patients who were not
receiving medications for their disease were correctly classified.
Altogether, these findings document robust differences in brain
function between the PTSD and control groups that can be used for
differential diagnosis and which possess the potential for assessing
and monitoring disease progression and effects of therapy.

The synchronous neural interactions test is a test that is done by
having persons perform a simple task, while the magnetic signals from
their brain are being measured.  The process is called href="http://www.scholarpedia.org/article/Magnetoencephalogram">magnetoencephalography. 
The resulting record is called a magnetoencephalogram (MEG).  It
is similar to an electroencephalogram (EEG).  The difference is
that the EEG measures small electric currents.  The MEG measures
magnetic impulses.  These impulses are only slightly affected by
the intervening tissue (skull, skin, etc).  Therefore, it is
possible to get readings that are more precise.  The downside is
that it requires a more elaborate device, and a special,
magnetically-shielded, room.  Very few of these devices exist.


Patients for the study were recruited from a population of military
veterans.  A total of 74 patients were studied.  The patient
population consisted mostly of persons with PTSD related to
warfighting.  Some had PTSD linked to abuse during
childhood.  Some had non-combat trauma during adulthood.  The
majority were Vietnam veterans.  Fifty-six were receiving
medication for PTSD.

Many potential subjects were excluded:

To minimize subject burden, we did not contact veterans
with indicators of instability within the last 6 months (e.g. inpatient
medical or mental health treatment, significant changes in health or
medications, etc) or those with psychotic disorders based on medical
record review. We also excluded veterans with active substance use
disorders, serious chronic pain and other CNS disorders (e.g.
Parkinson’s disease, dementia, cerebral vascular accidents, etc).

The outcome was more robust than I would have expected:

Finally, of 18 non-medicated PTSD patients, only one was
misclassified and 17/18 = 94.4% were correctly classified. Similarly,
of the 56 medicated patients, only one was misclassified and 55/56 =
98.2% were correctly classified. These two classification proportions
between the non-medicated and medicated PTSD patients did not differ
statistically significantly.

Of course, it remains to be seen if this can be replicated, and if it
can be extended to a more diverse population.  There have been
many previous attempts to find clinically-useful biomarkers for
psychiatric conditions.  So far, none has emerge as being
generally applicable.

One of the problems is that attempts to extend the population under
study tend to lead to loss of diagnostic precision.  Notice the
list of exclusion criteria, applied to potential patients.  That
list would also exclude a large proportion of patients presenting for
assessment in a non-research-oriented clinic.  The exclusion of
persons with substance abuse is particularly troublesome.  Not
only does it narrow the population considerably, but it means that the
patients studied may not be typical of all patients with PTSD. 
(PTSD increases the risk of developing a substance abuse problem by a
factor of 4.5.)

Another problem is that most of the patients had PTSD related to
wartime trauma.  Although the population did include some civilian
trauma, it is not clear at this point how well this technique would
work in a civilian population.

A nice aspect of this study, and its outcome, is that it does not
appear to matter whether or not the patients were taking
medication.  However, it reamins to be seen if this will be true
generally. 

If this works well, can be replicated, and can be extended to a general
population, it could be helpful in clinical use.  As it happens,
there is already a great deal of controversy over the diagnosis,
particujlarly with regard to disability benefits.  Our very own
David Dobbs (Neuron Culture) has been href="http://scienceblogs.com/neuronculture/2009/03/the_ptsd_trap.php">waving
a caution flag for a while.  Mike Dunford (The Questionable
Authority) has a href="http://scienceblogs.com/authority/2009/03/ptsd_mental_health_and_the_mil.php">roundup
of reactions to that issue, including his own take on it.

___________
Citation:
title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.jtitle=Journal+of+Neural+Engineering&rft_id=info%3Adoi%2F10.1088%2F1741-2560%2F7%2F1%2F016011&rfr_id=info%3Asid%2Fresearchblogging.org&rft.atitle=The+synchronous+neural+interactions+test+as+a+functional+neuromarker+for+post-traumatic+stress+disorder+%28PTSD%29%3A+a+robust+classification+method+based+on+the+bootstrap&rft.issn=1741-2560&rft.date=2010&rft.volume=7&rft.issue=1&rft.spage=16011&rft.epage=&rft.artnum=http%3A%2F%2Fstacks.iop.org%2F1741-2552%2F7%2Fi%3D1%2Fa%3D016011%3Fkey%3Dcrossref.48579e6cb5e6612ef21b23501d4e58ca&rft.au=Georgopoulos%2C+A.&rft.au=Tan%2C+H.&rft.au=Lewis%2C+S.&rft.au=Leuthold%2C+A.&rft.au=Winskowski%2C+A.&rft.au=Lynch%2C+J.&rft.au=Engdahl%2C+B.&rfe_dat=bpr3.included=1;bpr3.tags=Psychology%2CHealth%2CNeuroscience%2CPsychiatry%2C+Neural+Engineering%2C+Abnormal+Psychology">Georgopoulos,
A., Tan, H., Lewis, S., Leuthold, A., Winskowski, A., Lynch, J., &
Engdahl, B. (2010). The synchronous neural interactions test as a
functional neuromarker for post-traumatic stress disorder (PTSD): a
robust classification method based on the bootstrap style="font-style: italic;">Journal of Neural Engineering, 7

(1) DOI: href="http://dx.doi.org/10.1088/1741-2560/7/1/016011">10.1088/1741-2560/7/1/016011

Comments

  1. #1 Pietr
    February 8, 2010

    What an exciting post! There are a number of diagnostic problems that truly do exist but biomarkers are not available. Therefore, their diagnosis and treatment is downplayed in allopathic medicine and those in integrative medicine see so many of the sufferers.

    Chronic Fatigue Immunodeficiency
    Fibromyalgia
    Chemical Hypersensitivity

    and other conditions with protean symptoms have many common features with PTSD. IMHO, they will all be found to have diagnostic and therapeutic similarities. I hope that this powerful tool can step in and prove those with these conditions won’t have to fight diagnostic inertia for much longer.

  2. #2 JMG
    February 10, 2010

    One thing I don’t like in this paper is that they don’t give any argument or explanation of the mechanism behind the diagnosis. Shine a light into the eyes of PTSD sufferers, then diagnose? What an auditory stimuli? Where’s the reasoning why. It just seems very naive to diagnose a complicated neurological/psyhological disorder by letting a patient sit and stare into a light and comparing the reaction to a control subject. Maybe I’m just missing something here, as a small-time EEG researcher.

  3. #3 Meremark
    March 18, 2010

    -
    PTSD: Hard to find (diagnostically), easy to fix (therapeutically). Or vice versa. Maybe perhaps.

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    Full text HERE:
    Psychedelic Healing? – Hallucinogenic drugs, which blew minds in the 1960s, soon may be used to treat mental ailments, By David Jay Brown, Scientific American Mind, December 07

    -

    [Original web version behind paywall at http://www.sciam.com/article.cfm?id=psychedelic-healing&sc=WR_20080108 ]

    Mind-Bending Therapies

    * The drugs that put the “psychedelic” into the sixties are now the subject of renewed research interest because of their therapeutic potential.

    * Psychedelics such as LSD and the compound in magic mushrooms could ease a variety of difficult-to-treat mental illnesses, such as chronic depression, post-traumatic stress disorder, and drug or alcohol dependency.

    * Clinical trials with various substances are now under way in humans.

    -

    Mind-altering psychedelics are back — but this time they are being explored in labs for their therapeutic applications rather than being used illegally. Studies are looking at these hallucinogens to treat a number of otherwise intractable psychiatric disorders, including chronic depression, post-traumatic stress disorder, and drug or alcohol dependency.

    The past 15 years have seen a quiet resurgence of psychedelic drug research as scientists have come to recognize the long-underappreciated potential of these drugs. In the past few years, a growing number of studies using human volunteers have begun to explore the possible therapeutic benefits of drugs such as LSD, psilocybin, DMT, MDMA, ibogaine and ketamine.

    Much remains unclear about the precise neural mechanisms governing how these drugs produce their mind-bending results, but they often produce somewhat similar psychoactive effects that make them potential therapeutic tools.

    Current studies are focusing on psychedelic treatments for cluster headaches, depression, obsessive-compulsive disorder (OCD), severe anxiety in terminal cancer patients, post-traumatic stress disorder (PTSD), alcoholism and opiate addiction. New drugs must pass three clinical milestones before they can be marketed to the public, called phase I (for safety, usually in 20 to 80 volunteers), phase II (for efficacy, in several hundred subjects) and phase III (more extensive data on safety and efficacy come from testing the drug in up to several thousand people). All the studies discussed in this article have received government approval, and their investigators are either in the process of recruiting human subjects or have begun or completed research on human subjects in the first or second stage of this trial process.

    Psychiatrist Michael Mithoefer in Charleston, S.C., is running an MDMA study for treatment-resistant PTSD victims of crime, war or childhood sexual abuse. So far 17 out of 20 such subjects have already undergone the experimental therapy. “At this point the results are very promising,” Mithoefer says. “I think we’re seeing pretty strong, robust effects in some people. I hasten to add these are preliminary findings—we’re not ready to draw conclusions yet. But assuming it keeps going this way for the rest of the study, it certainly seems that there’s very good reason to go on to larger phase III trials.”

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