Quantifying the axonal pathways directly stimulated in therapeutic subcallosal cingulate deep brain stimulation

Area of Science:

• Neuroscience
• Neurosurgery
• Computational Psychiatry

Background:

• Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is an experimental therapy for treatment-resistant depression.
• Current SCC DBS targeting relies on computational models, but simpler models limit precision in estimating pathway activation.

Purpose of the Study:

• To evaluate SCC DBS using detailed patient-specific field-cable modeling in treatment-resistant depression responders.
• To identify specific axonal pathways activated by SCC DBS and their correlation with therapeutic response time.

Main Methods:

• Utilized field-cable modeling, the most detailed patient-specific approach, for SCC DBS evaluation in six responders.
• Quantified activation of forceps minor (FM), cingulum bundle (CB), uncinate fasciculus (UF), and frontal pole connections (FP).
• Employed linear regression with percentage of activated axons as predictors for time to stable response (TSR).

Main Results:

• Stimulation of left and right cingulum bundles (CB) and forceps minor (FM) appear to be the most likely therapeutic targets for SCC DBS.
• The right CB alone predicted 84% of the variation in TSR.
• A positive correlation between right CB activation and TSR suggests excessive stimulation may delay recovery.

Conclusions:

• Left/right CB and FM are probable therapeutic targets for SCC DBS in treatment-resistant depression.
• Right CB activation is a strong predictor of stable response time.
• Optimal stimulation parameters for the right CB are crucial to avoid protracted recovery.