Where Should Deep Brain Stimulation Be Applied to Best Treat Obsessive-Compulsive Disorder?

What you need to know

• Deep brain stimulation of two key brain regions - the anterior limb of the internal capsule and an area near the bed nucleus of the stria terminalis - was associated with the best improvements in obsessive-compulsive symptoms.
• Stimulating the nucleus accumbens led to less optimal outcomes compared to surrounding areas.
• The optimal stimulation sites for improving obsessive-compulsive symptoms overlapped partially with those for depression and anxiety.

Targeting Deep Brain Stimulation for Severe OCD

For patients with severe, treatment-resistant obsessive-compulsive disorder (OCD), deep brain stimulation (DBS) can offer hope when other therapies have failed. However, figuring out exactly where in the brain to apply this stimulation has been challenging. Different research groups have targeted various brain regions, but it’s been unclear which locations work best.

A new study brings some clarity to this issue by analyzing data from 82 patients with OCD who received DBS at multiple medical centers. The researchers used advanced brain imaging and modeling techniques to map out which stimulation sites were associated with the greatest symptom improvements.

Two Key Target Regions Identified

The study found two main “sweet spots” in the brain where DBS was linked to optimal reductions in OCD symptoms:

1. A region in the anterior limb of the internal capsule (ALIC). The ALIC is a bundle of nerve fibers that connects areas of the frontal lobe to deeper brain structures.

2. An area behind the anterior commissure, near the bed nucleus of the stria terminalis (BNST) and inferior thalamic peduncle (ITP). The BNST is part of the extended amygdala and plays a role in anxiety and fear responses. The ITP connects the thalamus to other brain regions.

Importantly, stimulating the nucleus accumbens - a region that has been targeted in some previous OCD studies - was associated with less optimal symptom improvement compared to the surrounding areas.

How the Study Was Conducted

The researchers combined data from 58 patients at 6 different medical centers to create detailed 3D maps showing how DBS outcomes related to stimulation location. They then validated their findings using data from an additional 24 patients at two other centers.

For each patient, they used brain scans to pinpoint exactly where the DBS electrodes were placed. They also modeled the electrical field produced by the stimulation. By correlating these electrical field maps with patients’ symptom improvements, they could identify the most effective stimulation sites across the whole group.

This “sweet spot” mapping approach revealed consistent patterns across patients, despite differences in the exact surgical targets used at different medical centers.

Overlapping Effects on Depression and Anxiety

Many patients with OCD also experience depression and anxiety. The researchers found that the optimal stimulation sites for improving OCD symptoms partially overlapped with those for depression and anxiety:

• The ALIC sweet spot was associated with improvements in OCD symptoms, depression, and anxiety.
• The more posterior sweet spot near the BNST/ITP was linked to improvements in OCD and depression, but not anxiety.

This suggests that carefully targeted stimulation may be able to address multiple symptoms simultaneously in many patients.

Implications for DBS Therapy

These findings have important implications for refining DBS therapy for OCD:

1. They provide a roadmap for neurosurgeons to more precisely target electrode placement.

2. For patients who have already had DBS electrodes implanted, the results could guide programming of which specific electrode contacts to activate.

3. The identification of two distinct sweet spots opens the door to potentially tailoring the stimulation target based on a patient’s specific symptom profile.

4. The finding that stimulating the nucleus accumbens proper leads to suboptimal outcomes suggests that targeting just above or behind this structure may be more effective.

Dr. Andreas Horn, one of the study’s senior authors, commented: “Our results suggest how to refine targeting of DBS in OCD and may be helpful in guiding DBS programming in existing patients.”

Limitations and Future Directions

While this study represents a major step forward, the authors note some limitations:

• The data came from multiple centers with some differences in assessment methods and follow-up times.
• The study was retrospective, analyzing existing data rather than prospectively testing different targets.
• The modeling of electrical fields in the brain, while advanced, still involves some approximations.

Future research could address these limitations through prospective, standardized studies directly comparing different stimulation targets. Additionally, as DBS technology advances to allow more precise steering of electrical fields, it may become possible to stimulate the identified sweet spots even more selectively.

Conclusions

• This large study identified two key brain regions where deep brain stimulation produces optimal improvements in OCD symptoms.
• Stimulating the nucleus accumbens itself appears less effective than targeting nearby regions.
• The findings provide a guide for neurosurgeons to refine DBS targeting and programming.
• Further research is needed to prospectively test these optimal stimulation sites and tailor targeting to individual patients.

For patients with severe, treatment-resistant OCD, these results offer hope for more consistently effective DBS therapy. As Dr. Garance Meyer, the study’s lead author, noted: “By mapping the brain’s ‘sweet spots’ for DBS in OCD, we’re moving closer to reliably providing relief for those suffering from this debilitating condition.”