Specific DBS Targets under Investigation

Subcallosal Cingulate (SCC)

THE CIRCUITS INVOLVED IN DEPRESSION - CASE STUDY
Table of Contents
Introduction.............................................................................................................................................2
Rationale.................................................................................................................................................2
Results to Date........................................................................................................................................3
Surgical and Device-Related....................................................................................................................4
Discontinuation.......................................................................................................................................4
References...................................................................................................................................................5

1
Introduction
Major depressive disorder (MDD) is increasingly recognised as a multidimensional disease that
is responsible for the wide range of depressed signs of diverse underlying circuits. Target circuit
function neuromodulator approaches to relieve symptoms. In some neurological conditions with
recognised circuit disorder (MSD), including motion disorders, deep brain stimulation (DBS) is
an effective therapy. DBS has been proposed as a therapy possible for estimated 10 percent of
patients with treatment-resistant depression due to this effectiveness (TRD). The collection of
theoretically appropriate stimulus goals is an apparent first criterion. Additional logic lines led to
many applicant goals for TRD DBS research. The following tactics are highlighted.

Rationale
The SCC was originally designated as a target for DBS depression because of elevated sadness
involvement, over-activity in MDD and normalization with antidepressant therapy. Pathological
over-activity is hypothesized in order to free from a recurrent depressive mood condition.
Modulation of SCC also has the ability, considering how interconnected it is to regions that have
nonmood symptoms of depression, to influence other symptoms of depression. Hypothalamus,
brains and insula connections make it possible to modulate neurovegetative effects of the
abnormal SCC. Reciprocal relations of pre-facing, orbit-frontal, anterior and posterior cingulate
medial and subcortical systems such as the SCC medium affect emotional, hedonic and
motivating signs of depression.

2
Results to Date
DBS of the white substance next to Brodmann Area 25 has been treated to six subjects in 2005.
From this time, forward findings have been released from eight treatment centers for 77 patients
(including seven patients with Type II bipolar disorder). Most trials included open label
stimulation, with one blind placebo lead-in month and a minimal blind discontinuation period
stopped due to health issues about sluggish recuperation of previously achieved clinical reaction
after few weeks of reactivated stimulation.

The aforementioned findings show the clear trend and timeframe of persistent behavioural results
in several individual trials, although a large randomized sham-controlled clinical trial has yet to
be conducted. Of course, while the requirements for inclusion and removal, surgical procedures
and algorithms are straightforward, these identical findings are used in order to optimize the
operation – both of them possibly vital to the process. To date the best SCC white matter goal
has been established and the surgical technique has been refined. Traditional anatomical
targeting did not identify responsive vs. non-responders target regions specifically. New
evidence shows that the optimal goal requires the intersection and stimulation of three separate
tracts which meet at the centre of the subcallosal — the unclosed fasciculus, cingulum and minor
forceps.

3
Surgical and Device-Related
Complications of DBS can include stroke, seizure, bleeding, and adverse consequences of
anesthesia, as can other neurosurgical treatments. The discomfort and infections are normal after
surgery. Battery failures or scar-tissue formation may result in device-related problems such as
broken leads or extension cables. This possible adverse effect may be anticipated in the case of
an international surgical implantation and there are inadequate evidence to identify any
discrepancies between instruments or surgical objectives, considering the comparatively limited
number of studies up to now. In addition to surgery, adverse effects of DBS may indicate the
malfunction of the drug, symptoms related to stimulus, non-response therapeutic impact or
therapy loss.

Discontinuation
Depression symptoms are systematically exacerbated with a deliberate or unintended
interruption. Several reports explain unintentional discontinuations due to battery fatigue,
unintended turning off or other system malfunction. They also result in a lack of anti-depressant
impact, even after years of chronic stimulus. The return to signs of depression normally occurs
for 1 to 6 weeks. Notably, no sudden mood shifts with an acute stop make the conduct of medical
tests such as an EKG at risk.

4
References
Crowell, A. L., 2014. Toward an Understanding of the Neural Circuitry of Major Depressive Disorder
Through the Clinical Response to Deep Brain Stimulation of Different Anatomical Targets. Current
Behavioral Neuroscience Reports volume, Volume 1, p. 55–63.

PE, H. & HS, M., 2011. Stuck in a rut: rethinking depression and its treatment. Trends Neurosci.. 34(1), p.
1–9.

RA, G. & PJ, H., 2011. A morphometric study of glia and neurons in the anterior cingulate cortex in mood
disorder.. Affect Disord, 133(2), p. 328–32.