Characterization of the thalamic–subthalamic circuit involved in the placebo response through single-neuron recording in Parkinson patients

The placebo effect, or response, is a complex phenomenon whereby an inert treatment can induce a therapeutic benefit if the subject is made to believe that it is effective. One of the main mechanisms involved is represented by expectations of clinical improvement which, in turn, have been found to either reduce anxiety or activate reward mechanisms. Therefore, the study of the placebo effect allows us to understand how emotions may affect both behavior and therapeutic outcome. The high rate of placebo responders in clinical trials of Parkinsonʹs disease provided the motivation to investigate the biological underpinnings of the placebo response in Parkinsonian patients. The placebo effect in Parkinsonʹs disease is induced through the administration of an inert substance which the patient believes to improve motor performance. By using this approach, different behavioral and neuroimaging studies have documented objective improvements in motor performance and an increase of endogenous dopamine release in both the dorsal and ventral striatum. Recently, single-neuron recording from the subthalamic and thalamic regions during the implantation of electrodes for deep brain stimulation has been used to investigate the firing pattern of different neurons before and after placebo administration. The results show that the subthalamic nucleus, the substantia nigra pars reticulata, and the ventral anterior thalamus are all involved in the placebo response in Parkinson patients, thus making intraoperative recording an excellent model to characterize the neuronal circuit that is involved in the placebo response in Parkinsonʹs disease as well as in other disorders of movement.