The role of expectation and conditioning for motor and cognitive effects in subthalamic deep brain stimulation of Parkinson's disease

• Applicant: Professor Dr. Alfons Schnitzler
• Subject Area: Human Cognitive and Systems Neuroscience ; Personality Psychology, Clinical and Medical Psychology, Methodology
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 138279939

In Parkinson’s disease (PD), alterations in cortical and subcortical oscillatory activity are considered to be a pathophysiological mechanism underlying motor symptoms of the disease. While oscillations in the beta-band are pathologically increased, oscillations in the gamma-band are reduced in PD-patients. Dopamine replacement therapy with dopamine agonists and the dopamine precursor levodopa as well as deep brain stimulation normalize these pathologically altered oscillations, which is associated with improvement in motor symptoms. However, to date, the role of oscillations as neurophysiological underpinnings of placebo responses and expectation-induced motor improvement in the treatment of PD has not been investigated. Thus, one of the major aims of the project is the characterization of (sub-)cortical oscillatory neuronal mechanisms underlying placebo responses in motor function we observed in the first funding period in PD-patients. Therefore, we will investigate i) the effect of expectation regarding the therapeutic impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on cortical oscillations non-invasively using magnetoencephalography (MEG). Moreover, ii) the effect of expectation regarding the dopamine agonist apomorphine will be studied on oscillatory activity in the STN. Thus, in PD-patients who have recently undergone surgery for the implantation of DBS-electrodes, local field potentials in the STN will be recorded using the temporarily externalized electrode leads. Besides the characterization of oscillatory mechanisms, a further aim of the project is the identification of behavioral modulators of placebo responses in PD. In the field of experimental pain, there is accumulating evidence that prior experience of benefit - experimentally induced by conditioning procedures with an effective treatment - is crucial for the occurrence, magnitude and duration of placebo responses. Hence, a further study of this project will investigate iii) the effect of conditioning pharmacological responses with an antiparkinsonian medication on the magnitude of placebo responses in PD-patients. Altogether, this project aims at providing new clinically relevant insights into the neurophysiological mechanisms and behavioral modulators of placebo responses in PD.

• DFG Programme: Research Units
• Subproject of: FOR 1328: Expectation and Conditioning as Basic Processes of the Placebo and Nocebo Response
• Participating Person: Dr. Lars Wojtecki