fMRI during active GPi DBS uncovers target-specific networks

Improved understanding of target-specific changes in brain activity during deep-brain stimulation (DBS) for Parkinson's disease (PD) may refine target selection. Here, we study the network effects of active DBS using functional magnetic resonance imaging (fMRI) during stimulation of the subthalamic nucleus (STN) and globus pallidus internus (GPi). About 36 PD patients (62.5 ± 8.1 years, 18 GPi-DBS, 39% female) underwent prospective fMRI during active DBS. DBS produced distributed cortical modulation associated with clinical improvement at the group level. Network modeling revealed symptom-specific coupling, with somatomotor network modulation significantly associated with gait improvement (ΔR² = 0.40, p_FDR = 0.03) and showing a weaker association with bradykinesia improvement (ΔR² = 0.32, p_FDR = 0.06). Unexpectedly, somatomotor network modulation showed a nominal association with variability in verbal fluency outcomes (ΔR² = 0.28, p_FDR = 0.08), whereas language and cognitive networks demonstrated minimal explanatory value. A comparable relationship between network modulation and verbal fluency was not observed in STN-DBS. These findings demonstrate that DBS therapeutic effects are best understood as modulation of distributed functional networks rather than focal regions, with target-dependent network coupling potentially underlying differential cognitive outcomes.