SCC-DBS Pathway Engagement Linked to Depression Response

Key Takeaways

• Among patients with treatment-resistant depression receiving bilateral SCC-DBS, responders had less spatial variation in reconstructed activated-tissue volumes than nonresponders.
• A focal stimulation cluster was associated with improvement in depressive symptoms.
• Failure to engage the left cingulum bundle and medial uncinate fasciculus was associated with less therapeutic benefit.

For patients with treatment-resistant depression, subcallosal cingulate (SCC) deep brain stimulation (DBS) electrical stimulation can extend beyond the immediate electrode location, making the relationship between circuit engagement and changes in depressive symptoms difficult to characterize.

Investigators retrospectively assessed 131 patients with treatment-resistant depression from three independent cohorts in an American Journal of Psychiatry connectomic study. All had received bilateral SCC-DBS using site-specific targeting methods.

Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale (HAM-D), and response was defined as a reduction of at least 50% in HAM-D score. Using each patient's DBS settings, investigators reconstructed volumes of tissue activated by stimulation. They then used voxel-wise probabilistic stimulation mapping to examine where activation aligned with improvement and normative fiber-wise analyses to assess engagement of white-matter connections. These methods compared observed stimulation patterns in responders and nonresponders.

Responders' reconstructed volumes of tissue activated showed less spatial variability than those of nonresponders. Probabilistic mapping also identified a focal cluster whose stimulation was associated with clinical improvement. Fiber-wise analyses associated engagement of predefined white-matter tracts used in connectome-based targeting with therapeutic benefit. Specifically, failure to activate the left cingulum bundle and medial uncinate fasciculus was associated with diminished therapeutic effects.

Because patients had already undergone SCC-DBS using site-specific targeting methods, the pathway associations do not show what would have happened if the same patients had received a different targeting approach. The comparison was between observed clinical outcomes and reconstructed stimulation patterns, not between prospectively assigned surgical strategies. Consequently, the association between pathway engagement and improvement cannot establish that changing the targeting method would improve outcomes for people with treatment-resistant depression.

The authors interpret engagement of the lateralized cingulum bundle and medial uncinate fasciculus as potentially relevant to sustained improvement after SCC-DBS.

Clinician Questions

Does connectome-based SCC-DBS targeting outperform anatomical-landmark targeting for treatment-resistant depression?

For SCC-DBS in treatment-resistant depression, the authors suggest that connectome-based targeting might have an advantage over approaches based solely on anatomical landmarks or normative atlases.