Optimal Target for Deep Brain Stimulation for Depression

The strongest evidence exists for Broadman Area 25 in the subcallosal cingulate gyrus (SCG) as target for deep brain stimulation in treatment resistant depression. This area in the brain is depicted in the figure above and is from the most important publication about DBS and depression in Neuron march 2005 by Helen Mayberg. Functional neuroimaging as well as antidepressant treatment effects suggest that this area plays an important role in modulating negative mood states. A decrease in activity is reported with clinical response to antidepressants and electroconvulsive therapy (ECT).

But depression is not a disease of a single brain region nor neurotransmitter system. It is now generally viewed as a systems-level disorder affecting integrated pathways linking select cortical, subcortical, and limbic brain regions with their related neurotransmitter systems.

Suggestions of other brain localizations for treatment with DBS for depression comes from case reports with DBS for other indications than depression. These localizations have been described in a peer reviewed article with excelent graphics.

In a recent study done by the “Mayberg group”, Toronto, Canada, the autors compared the location of the electrode contacts in responders and nonresponders to DBS of the subcallosal cingulate gyrus (SCG) and correlated the results with clinical outcome to help in identifying the optimal target within the region.

On postoperative MRI scans the researchers did complicated mapping procedures to pin point the locations of the active contacts on the implanted electrodes. There was no difference when the right and left electrodes were compared in patients. So both electrodes were exactly placed on each side (hemisphere). The only significant difference they found between responders and nonresponders was that electrodes in patients who responded were in a slightly more ventral position relative to the anatomical landmarks used in the medial prefrontal lobe. This difference between responders and nonresponders did not exceed 1,5 mm. The authors is not likely to be of clinical significance, according to the authors. This small difference is probably unimportant compared to the clinical features of the patient for the outcome of the DBS procedure in depression. Another limiting factor on this research is the small sample size, in larger groups these results might differ.

What we can conclude based on our findings is that within the small targeted region of the SCG, the location of the electrode contacts did not determine outcome.

This article also describes a detailed method for a more standardized method for targeting the SCG with DBS for depression. This is to technical to reproduce in this post but those working with DBS for depression should have a look at this procedure. From this study it is still not clear whether DBS of other brain areas might be more superior in efficacy. And is brain area more important than clinical features of the patient or do the areas differ for different types of depression? All very interesting questions and topic for more research on DBS.