Subcortical short-term plasticity elicited by deep brain stimulation

Objective: To investigate local short-term neuroplasticity elicited by subthalamic, thalamic, and pallidal deep brain stimulation (DBS) for movement disorders. Methods: During DBS surgery, we delivered pairs of stimulus pulses with both circular and directional leads across 90 interstimulus intervals in 17 participants and recorded local field potentials from unused contacts on the implanted electrode array. We removed the stimulus artifact, validated the neural origin of the underlying signals, and examined short-term plasticity as a function of interstimulus interval and DBS target, using linear mixed effects models. Results: DBS evokes short latency local field potentials that are readily detected with both circular and directional leads at all stimulation targets (0.31 +/- 0.10 msec peak latency, mean +/- SD). Peak amplitude, area, and latency are modified strongly by interstimulus interval (P < 0.001) and display absolute and relative refractory periods (0.56 +/- 0.08 and 2.94 +/- 1.05 msec, respectively). We also identified later oscillatory activity in the subthalamic-pallidal circuit (4.50 +/- 1.11 msec peak latency) that displays paired pulse facilitation (present in 5/8 subthalamic, 4/5 pallidal, and 0/6 thalamic trajectories, P = 0.018, Fisher's exact test), and correlates with resting beta frequency power (P < 0.001), therapeutic DBS frequencies, and stimulation sites chosen later for therapy in the ambulatory setting (P = 0.031). Interpretation: Paired DBS pulses synchronize local circuit electrophysiology and elicit short-term neuroplasticity in the subthalamic-pallidal circuit. Collectively, these responses likely represent the earliest detectable interaction between the DBS pulse and local neuronal tissue in humans. Evoked subcortical field potentials could serve as a predictive biomarker to guide the implementation of next-generation directional and adaptive stimulation devices.