Electrophysiological Network Mapping of Deep Brain Stimulation Outcomes in Parkinson’s disease

Deep brain stimulation (DBS) is one of the most successful advances in translational neuroscience and an established treatment for individuals with Parkinson’s disease. However, the remarkable effects on motor symptoms and quality of life strongly depend on accurate electrode positioning and precise DBS programming. Despite its benefits, DBS programming remains a time-consuming task that burdens both patients and healthcare providers. Therefore, biomarkers are needed to inform and streamline the DBS programming process. 

Electrophysiological network mapping is a novel approach that can map DBS outcomes to brain networks defined by electrophysiological markers of connectivity between the stimulation site (subthalamic nucleus, STN) and the cortex. We tested two electrophysiological measures: (1) cortical responses to subthalamic stimulation pulses (DBS-evoked potentials) and (2) Cortico-STN connectivity measures in the frequency domain (e.g., coherence). 

DBS-evoked potentials capture the cortical response to each DBS pulse delivered to the STN. In our previous work, we identified a cortical pattern of DBS-evoked potentials aligning with the basal ganglia-thalamo-cortical network (Bahners et al., 2023). By extracting the DBS-evoked potential amplitudes from these regions, we found a relationship between motor cortex evoked potential amplitudes and motor performance. Given the previous lack of systematic studies on this relationship, our results represent an important prerequisite for using DBS-evoked potentials in clinical programming. 

In a recent study involving 30 individuals with Parkinson’s disease, we developed a novel approach that leverages both the temporal and spatial patterns of evoked potentials (Bahners et al., 2024). This method generates an evoked potential map across all recorded dry EEG channels over time (time x channel map) and correlates evoked potential amplitudes with individual improvements in motor performance. The outcome is a correlation matrix (R-matrix) representing the “optimal” evoked potential pattern. By spatially comparing this optimal pattern to an individual evoked potential pattern, spatial similarity can be used to estimate individual improvements. Notably, this method successfully identified the optimal DBS contact in a prospective cohort unseen by the R-matrix model. Given the use of dry EEG, this method could be easily implemented in DBS outpatient clinics to optimize DBS parameters in a time-efficient manner. 

The second measure used to map DBS outcomes to brain networks was Cortico-STN coherence, a measure of connectivity in the frequency domain. To this end, we utilized a unique dataset of combined STN local field potential and MEG recordings collected over almost 15 years across two German movement disorder centers in Düsseldorf and Berlin. This dataset enabled us to identify specific cortical regions that exhibit synchronized activity with the STN in different frequency bands. Applying the same method as in the case of DBS-evoked potentials, we mapped frequency- and symptom-specific outcome networks, reflecting the optimal connectivity pattern with the STN stimulation site. 

These results pave the way for a new approach to DBS network mapping that enables us to resolve the electrophysiological signatures relevant for DBS outcomes in Parkinson’s disease and other movement disorders. Ultimately, we envision a comprehensive electrophysiological examination after DBS surgery that will objectively identify the optimal DBS settings for individual patients. 

References

1. Bahners, B. H., Goede, L. L., Meyer, G. M., Poser, L., Hart, L. A., Pijar, J., Rajamani, N., Hollunder, B., Madan, S., Oxenford, S., Waterstraat, G., Curio, G., Schnitzler, A., Florin, E., Kühn, A. A., Fox, M. D., & Horn, A. (2024). Evoked response signatures explain deep brain stimulation outcomes. medRxiv, 2024.10.04.24314308. https://doi.org/10.1101/2024.10.04.24314308

2. Bahners, B. H., Spooner, R. K., Hartmann, C. J., Schnitzler, A., & Florin, E. (2023). Subthalamic stimulation evoked cortical responses relate to motor performance in Parkinson’s disease. Brain Stimulation, 16(2), 561–563. https://doi.org/10.1016/j.brs.2023.02.014