Update on Deep Brain Stimulation

href="http://www.researchblogging.org"> alt="ResearchBlogging.org"
style="border: 0pt none ;">
rel="tag">Deep Brain Stimulation (DBS) currently
is under investigation for treatment of sever, treatment-resistant
depression (TRD).  It is not really news.  I href="http://trots.blogspot.com/2005/03/implantable-devices-for-major.html">wrote
about it in 2005.  The background information in the
earlier post still is pertinent, so I won't repeat that now.
 Briefly, though, the treatment consists of surgical
implantation of a pacemaker-like device.  The device has wires
that go into the brain (area 25, the subgenual cingulate area).

The study reported in 2005 was promising, but it included only six
patients.  Four patients responded, and maintained response
for six months.  That is kind of neat, but the number of
patients and the duration of response were both way too small to get
excited about.  

In the meantime, we've seen reports about the application of href="http://scienceblogs.com/purepedantry/2006/12/brain_stimulation_is_an_effect.php">DBS
for Parkinson's disease; for persons with a
minimally-conscious state after traumatic brain injury ( href="http://scienceblogs.com/retrospectacle/2007/08/implanted_electrodes_boost_bra.php">1
and for Alzheimer's Disease ( href="http://www.shockmd.com/2008/01/31/deep-brain-stimulation-for-alzheimers-disease/">1

In May, href="http://www.shockmd.com/2008/05/24/cognitive-safety-of-deep-brain-stimulation-for-treatment-resistant-depression/">Dr.
Shock provided an update on the cognitive safety of DBS when
used to TRD.  Bottom line: it is very safe, with no cognitive
problems noted.  That is obviously good, especially if one
also plans to use it for treatment of dementia.

In July, Mo, href="http://scienceblogs.com/neurophilosophy/2008/07/clinical_trial_of_deep_brain_s.php">writing
at Neurophilosophy, provided a nice summary of the more
recent report about the use of DBS for TRD; this report described the
results with more patients, with a longer follow-up period.  

At that time, the article had been epublished-ahead-of-print, and only
the abstract was openly available.  Now, the final published
article is available.  Not only that, but the journal selected
it to be one of their few open-access articles.

Cingulate Gyrus Deep Brain Stimulation for Treatment-Resistant


A preliminary report in six patients suggested that deep brain
stimulation (DBS) of the subcallosal cingulate gyrus (SCG) may provide
benefit in treatment-resistant depression (TRD). We now report the
results of these and an additional 14 patients with extended follow-up.


Twenty patients with TRD underwent serial assessments before and after
SCG DBS. We determined the percentage of patients who achieved a
response (50% or greater reduction in the 17-item Hamilton Rating Scale
for Depression [HRSD-17]) or remission (scores of 7 or less) after
surgery. We also examined changes in brain metabolism associated with
DBS, using positron emission tomography.


There were both early and progressive benefits to DBS. One month after
surgery, 35% of patients met criteria for response with 10% of patients
in remission. Six months after surgery, 60% of patients were responders
and 35% met criteria for remission, benefits that were largely
maintained at 12 months. Deep brain stimulation therapy was associated
with specific changes in the metabolic activity localized to cortical
and limbic circuits implicated in the pathogenesis of depression. The
number of serious adverse effects was small with no patient
experiencing permanent deficits.


This study suggests that DBS is relatively safe and provides
significant improvement in patients with TRD. Subcallosal cingulate
gyrus DBS likely acts by modulating brain networks whose dysfunction
leads to depression. The procedure is well tolerated and benefits are
sustained for at least 1 year. A careful double-blind appraisal is
required before the procedure can be recommended for use on a wider

The bottom line is that it still is too early to get excited, but it is
OK to allow yourself to get a warm glow of anticipation.  In a
population of patients with TRD, a response rate of 60% is
astonishingly good.  A remission rate of 35% is equally
remarkable.  The fact that those results held up for one year
is highly encouraging.

Treatment response was seen in the whole package of symptoms:

Deep brain stimulation was associated with global
improvements in
depressive symptomatology as measured by the mood, anxiety, somatic,
and sleep subcomponents of the HRSD scale.

The authors point out that the treatment "is adjustable and stimulation
is reversible."  This is different than other types of
psychosurgery, which are irreversible. ( href="http://scienceblogs.com/corpuscallosum/2008/08/my_picks_and_comments_from_arc.php">1

As sort of an added bonus, Lozano et. al. performed
neuroimaging (PET) in addition to the clinical outcome studies.


This shows definite, specific changes in brain activity.
 Moreover, it shows that the changes progress over time.
 (The changes are relative to baseline.)

The authors note that the changes is the immediate vicinity of the
electrodes are not the same as the effects downstream:

Of interest, opposite metabolic changes were present
at the target of stimulation, the subcallosal cingulate white matter,
and the immediately adjacent gray matter. In contrast to our previous
report using blood flow where only decreased SCG activity was observed,
we noted focal increases in metabolism in the immediate vicinity of the
stimulating electrode with decreases in metabolism in the adjacent
caudal subcallosal gray matter consistent with the previous blood flow
results (Figure 3, sagittal image, left). These results suggest that
there is a direct activation of the white matter at target that can
lead to either metabolic activation or inhibition in distinct remote
brain areas.

While this may not have immediate clinical significance, this kind of
descriptive study can turn out to have implications for further
research in basic neuroscience.  

-------- --------

Groovy citation:

Subcallosal Cingulate Gyrus Deep Brain Stimulation for
Treatment-Resistant Depression Biological
DOI: href="http://dx.doi.org/10.1016/j.biopsych.2008.05.034">10.1016/j.biopsych.2008.05.034

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Did the authors of this study examine potential changes in autonomic nervous system activity that might be produced by direct stimulation of this region of cingulate cortex? (Sorry, I don't have immediate access to the article.)

There is a wide range of evidence that this cortical region can directly influence heart rate, blood pressure and similar functions through inhibition of the sympathetic nervous system. This effect is believed to be mediated by direct projections from area 25 to the nucleus of the solitary tract and other brainstem nuclei (at least in rats). It seems to me that it might be important to examine this cortical-autonomic link because the autonomic nervous system plays an important role in emotions.

If psychiatrists had psychic powers, they would not need to use PET scans.

I did not see any mention in the article of assessment of autonomic function. I would like to think that adverse effects such as bradycardia or postural hypotension (or the opposite) would have been obvious, and would have been mentioned if they occurred, but that is an assumption.