The Deep Brain Stimulation Response Network in Parkinson's Disease Operates in the High Beta Band

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in patients with Parkinson's disease. Using functional MRI, optimal DBS response networks have been characterized. However, neural activity associated with Parkinsonian symptoms is magnitudes faster than what can be resolved by this method. While both spatial and temporal domains of these networks appear critical, no single study has yet investigated both domains simultaneously. Here, we aim to close this gap using subthalamic local field potentials that were concurrently recorded alongside whole-brain magnetoencephalography in a multi-center cohort of patients that underwent STN-DBS for the treatment of Parkinson's disease (N = 100 hemispheres). In every cortical vertex, cortico-subthalamic coupling was correlated with stimulation outcomes. This network spatially resembled fMRI-based findings (R = 0.40, P = 0.039) and explained significant amounts of variance in clinical outcomes (β _std = 0.30, P = 0.002), while theta-alpha and low beta coupling did not show significant associations with DBS response (theta-alpha: β _std = -0.02, P = 0.805; low beta: β _std = -0.08, P = 0.426). The 'optimal' high beta coupling map was robust when subjected to various cross-validation designs (10-fold cross-validation: R = 0.29, P = 0.009; split-half design: R = 0.31, P = 0.026) and was able to predict outcomes across DBS centers (R = 0.74; P ₍₁₎ = 8.9e-5). We identified a DBS response network that i) resembles the previously defined MRI network and ii) operates in the high-beta band. Maximal connectivity to this network was associated with optimal DBS outcomes and was able to cross-predict clinical improvements across DBS surgeons and centers.