Introduction Subthalamic deep brain stimulation (DBS) is beneficial when delivered at a high frequency. However, the effects of current amplitude and pulse width on subthalamic neuronal activity during high-frequency stimulation have not been investigated.

Methods In 20 patients with Parkinson’s disease each undergoing subthalamic DBS, we recorded single-unit subthalamic activity using one microelectrode, while a separate microelectrode was used to deliver 5–10 s trains of stimulation at 100 Hz using varying current amplitudes and pulse widths (44 neurons investigated).

Results Analysis of variance tests confirmed significant (p<0.001) main effects of both current amplitude and pulse width on subthalamic neuronal firing during stimulation and on poststimulus inhibitory silent periods. Prolonged silent periods were often followed by postinhibitory rebound burst excitations. Additionally, a significant (p<0.0001) correlation was found between neuronal firing and total electrical energy delivered (TEED). With TEED values≤31.2 µJ/s (associated with DBS parameters of ≤2.0 mA, 130 Hz stimulation frequency and 60 µs pulse width, assuming 1 kΩ impedance), neuronal firing was sustained at a rate of 32.4%±3.3% (mean±SE), while with values>31.2 µJ/s, neurons fired at only 4.3%±1.2%.

Conclusions Neuronal suppression is likely an important mechanism of action of therapeutically beneficial subthalamic DBS, which may underlie clinically relevant behavioural changes.