On the neural basis of deep brain stimulation evoked resonant activity

Abstract

Objective: Deep brain stimulation can be a remarkably effective treatment for Parkinson’s disease and other conditions; however, an electrophysiological feedback signal is needed to improve surgical accuracy and for optimising therapy according to patient needs. Evoked responses may provide such a signal, although it is crucial to determine that recorded potentials are of neural origin and not a consequence of stimulation artefacts. Here, we use several in vitro and in vivo methods to establish the neural basis of resonant deep brain stimulation evoked activity. Approach: Recordings were obtained from deep brain stimulation electrodes in saline, in feline brain regions not expected to produce resonant neural responses, and in fourteen subthalamic nuclei in people with Parkinson’s disease following stimulation with 60 μs per phase biphasic current pulses with different polarities. Main results: Electrodes in saline did not exhibit stimulation artefacts beyond 1 ms. Changing the pulse polarity reversed the stimulation artefact. Electrodes in feline brain elicited early latency activity (<5 ms); however, the activity did not resemble a decaying oscillation. Electrodes in human subthalamic nuclei evoked resonant neural activity that was not reversed by changing the pulse polarity. The latency of resonant peaks from stimuli with opposing polarities differed by about the expected amount and were strongly correlated (ρ = 0.998, p < 0.001). Resonant peak amplitudes were also strongly correlated (ρ = 0.945, p < 0.001). Significance: The absence of resonant activity in recordings from electrodes in saline and feline brain, in addition to findings that resonant activity occurs in the subthalamic nucleus but not neighbouring white matter regions, demonstrates that such activity is not an artefact of the stimulation and recording system. Furthermore, non-reversal of resonant activity with changing pulse polarity in human subthalamic nuclei indicates that it is independent from stimulation artefact. Thus, these methods provide strong evidence of the neural basis of deep brain stimulation evoked resonant activity.