Microelectrode recordings of single unit neuronal activity were used during stereotactic surgery to define the subthalamic nucleus for chronic deep brain stimulation in the treatment of Parkinson's disease. By using five parallel trajectories, often two to three microelectrodes allow us to recognize subthalamic nucleus (STN) neuronal activity. STN neurons were easily distinguished from cells of the overlying zona incerta and the underlying substantia nigra. During a typical exploratory track, we can observe a very low background noise in the zona incerta and almost complete absence of single cell recording. Penetration of the electrode tip into the STN is characterized by a sudden increase in background activity and single cell activity of spontaneously active neurons. The exit of electrode tip out of the STN corresponds to a decrease in background noise and a loss of single cell activity. Spontaneous neuronal activity increases again when the electrode tips enters the substantia nigra pars reticulata (SNr); however, the activity is less rich than in the STN, indicating a more cell-sparse nucleus. STN neurons are characterized by a mean firing rate of 42.30 +/- 22.00 spikes/sec (mean +/- SD). The STN cells exhibited irregular or bursty discharge pattern. The pattern of single cell activity in the SNr is a more regular tonic activity that can easily be distinguished from the bursting pattern in the STN. The most useful criteria to select a trajectory are (1) the length of an individual trajectory displaying typical STN activity, (2) the bursting pattern of activity, and (3) motor responses typical of the sensorimotor part of the nucleus. In conclusion, microelectrode recording of the subthalamic area improves the accuracy of targeting the STN.

Gait and balance disturbances typically emerge in advanced Parkinson’s disease with generally limited response to dopaminergic medication and subthalamic nucleus deep brain stimulation. Therefore, advanced programming with interleaved pulses was put forward to introduce concomittant nigral stimulation on caudal contacts of a subthalamic lead. Here, we hypothesized that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata improves axial symptoms compared with standard subthalamic nucleus stimulation. Twelve patients were enrolled in this 2 × 2 cross-over double-blind randomized controlled clinical trial and both the safety and efficacy of combined subthalamic nucleus and substantia nigra pars reticulata stimulation were evaluated compared with standard subthalamic nucleus stimulation. The primary outcome measure was the change of a broad-scaled cumulative axial Unified Parkinson’s Disease Rating Scale score (Scale II items 13–15, Scale III items 27–31) at ‘3-week follow-up’. Secondary outcome measures specifically addressed freezing of gait, balance, quality of life, non-motor symptoms and neuropsychiatric symptoms. For the primary outcome measure no statistically significant improvement was observed for combined subthalamic nucleus and substantia nigra pars reticulata stimulation at the ‘3-week follow-up’. The secondary endpoints, however, revealed that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata might specifically improve freezing of gait, whereas balance impairment remained unchanged. The combined stimulation of subthalamic nucleus and substantia nigra pars reticulata was safe, and of note, no clinically relevant neuropsychiatric adverse effect was observed. Patients treated with subthalamic nucleus and substantia nigra pars reticulata stimulation revealed no ‘global’ effect on axial motor domains. However, this study opens the perspective that concomittant stimulation of the substantia nigra pars reticulata possibly improves otherwise resistant freezing of gait and, therefore, highly warrants a subsequent phase III randomized controlled trial.