Volume-of-Tissue-Activated Matched Deep Brain Stimulation Parameters Can Elicit Spatially Similar, yet Temporally Distinct, Patterns of Cortical Activation Measured by Evoked Potentials

Introduction: Despite the extensive use of deep brain stimulation (DBS) for movement disorders, and novel applications for treatment-resistant psychiatric illness, the biophysics of neural stimulation and the significance and accuracy of often-used volume of tissue activated (VTA) is poorly characterized. To explore the accuracy and functional significance of VTA, we sought to characterize the stimulation-evoked responses in the human brain to varying stimulation parameters while holding constant the total modeled VTA. If VTA models are accurate, we hypothesized that maintaining a fixed VTA would lead to a similar set of activated brain areas.

Methods: In patients undergoing simultaneous implantation of sEEG and ventral-capsule/ventral-striatum and subcallosal cingulate (SCC) DBS as part of an investigational study of DBS for treatment-resistant depression, we delivered trains of single stimulation pulses, matching the VTA between blocks while varying stimulation amplitude and pulse width. We epoched signals from sEEG channels between 10 and 70 milliseconds after each pulse and used a Bayesian method to determine if the channel showed an evoked potential in response to stimulation.

Results: VTA-matched parameters elicited responses in similar brain areas across blocks in both patients (with some variability in the exact set of active sEEG contacts), supporting our initial hypothesis. However, evoked potential waveform characteristics such as the peak amplitude of the waveform, number of phases, and latency of the responses following the stimulation pulse often differed between varying pulse-width levels. This may point to additional functional significance of the underlying stimulation field properties beyond the modeled active volume.

Conclusion : Our results suggest that while VTA-matched stimulation parameters likely evoke neural responses in similar anatomic areas, the specific pattern and temporal dynamics of activation may depend on both patient-specific neuroanatomy and the exact electric field generated by each parameter set. Further characterization may lead to an improved understanding of the underlying biophysics of DBS.