Non-Human Primate: An Essential Building Brick in the Discovery of the Subthalamic Deep Brain Stimulation Therapy

The recent announcement that a Lasker award has been attributed to Professor Alim-Louis Benabid for pioneering the application of high frequency stimulation, named deep brain stimulation, of the subthalamic nucleus in patients suffering from Parkinson's disease prompts us to evoke the decisive role played by the non-human primate model in the discovery of this neurosurgical therapy, now regarded as the current therapeutic gold standard of the disease. The era of human functional surgery started in the 1950s by performing ablative procedures aiming to avoid the side effects of the commonly performed frontal lobotomy in the treatment of psychiatric illness (Spiegel et al., 1952). During surgery, intraoperative electrical stimulation was used from the beginning to explore the brain target prior to ablation. During the same period of time, Delgado et al. (1952) were the first to develop a technique of subcortical stimulation using chronically implanted electrodes connected to a subcutaneous receiver implanted in the scalp, a " Stimoceiver, " that could be controlled by radio waves. This technique of " radio communication with the brain " was initially developed for use in psychiatric patients. The chronological order of applications of chronic deep brain stimulation was first for psychiatry and behavior, then for pain and epilepsy. Deep brain stimulation for Parkinson's disease and other movement disorders was the last indication of the older era of chronic subcortical stimulation. Hariz and colleagues reported a detailed history of deep brain stimulation between 1947 and 1987 (Hariz et al., 2010). In the late 1980s, considerable progress was made in the understanding of the role played by the basal ganglia in the pathophysiology of Parkinson's disease (Albin et al., 1989) and the subthalamic nucleus was highlighted as an optimal therapeutic target. This small nucleus, the only excitatory glutamatergic structure of the basal ganglia network (Smith and Parent, 1988) playing a key role in movement control (DeLong, 1990), is considered as a driving force regulating the basal ganglia output nuclei; it was therefore suggested that activation of the subthalamic nucleus should inhibit movement and conversely its inhibition should be related to the release of movement. Back in 1927 it had already been reported that a focal lesion of the subthalamic area could induce hemiballismus, the manifestation of abnormal involuntary movements (Martin, 1927) and this association was reproduced later by lesion of the subthalamic nucleus in the non-human primate (Hammond et al., 1979). Single unit extracellular electrophysiology (Miller …