Left Prefrontal Connectivity Links Subthalamic Stimulation with Depressive Symptoms

Area of Science:

• Neuroscience
• Neurosurgery
• Psychiatry

Background:

• Subthalamic nucleus deep brain stimulation (STN-DBS) affects brain networks beyond the targeted area.
• The impact of STN-DBS on non-motor symptoms, particularly depression, is not fully understood.
• Varied effects of STN-DBS on depressive symptoms (improvement, worsening, or no change) necessitate further investigation.

Purpose of the Study:

• To investigate how electrode placement and structural connectivity influence changes in depressive symptoms after STN-DBS in Parkinson's disease patients.
• To identify specific brain network connections associated with mood changes post-STN-DBS.
• To develop predictive models for depressive symptom changes based on connectivity patterns.

Main Methods:

• Collected pre- and post-operative depressive symptom data from 116 Parkinson's disease patients across three centers.
• Reconstructed individual electrode placement and estimated volumes of tissue activated (VTAs).
• Integrated VTA data with normative connectome data to analyze structural connectivity and predict depressive symptom changes.

Main Results:

• Structural connectivity significantly correlated with changes in depressive symptoms following STN-DBS.
• A connectivity map trained on one cohort predicted depressive symptom changes in other cohorts, including an independent test set.
• Worsening of depressive symptoms was specifically linked to connections involving left prefrontal brain areas.

Conclusions:

• Electrode placement in the left subthalamic nucleus that impacts fibers to left prefrontal areas is associated with worsening depressive symptoms.
• Optimizing STN-DBS lead placement by avoiding these specific connections may help maximize mood improvement in Parkinson's disease patients.
• Understanding network-level effects is crucial for refining STN-DBS targeting for non-motor outcomes.