Effects of expectation on placebo-induced dopamine release in Parkinson disease. (Aug 2010)
“The anticipation of therapeutic benefit in response to placebo administration has been likened to the expectation of reward, particularly in patients with a chronic debilitating illness who have already experienced symptom relief from frequent doses of medication or other interventions.
Sarah C. Lidstone, PhD; Michael Schulzer, MD, PhD; Katherine Dinelle, MSc; Edwin Mak, BSc; Vesna Sossi, PhD; Thomas J. Ruth, PhD; Raul de la Fuente-Ferna´ndez, MD; Anthony G. Phillips, PhD; A. Jon Stoessl, MD.
Published on the archpsyc.ama-assn.org website, August 2010
The promise of sympton improvement that is elicited by a placebo is a powerful modulator of brain neurochemistry. Understanding the factors that modify the strength of the placebo effect is of major clinical as well as fundamental scientific significance. Several studies have demonstrated the critical role of expectation in the mechanism of the placebo effect. The expectation of symptom improvement is associated with endogenous dopamine release and changes in subthalamic nucleus neuronal firing in Parkinson disease (PD), the release of endogenous opioids and dopamine in placebo analgesia, and changes in brain glucose metabolism in depression. Manipulation of expectation has been shown to affect the clinical motor performance of PD patients.
The anticipation of therapeutic benefit in response to placebo administration has been likened to the expectation of reward, particularly in patients with a chronic debilitating illness who have already experienced symptom relief from frequent doses of medication or other interventions. In keeping with this view, placebos have been shown to activate reward circuitry, including stimulation of dopamine release in the ventral striatum. On presentation of a reward predicting cue, midbrain dopamine neurons display short phasic responses that encode the probability of reward delivery, the expected magnitude of the reward, and the product of these parameters, the expected reward value. This burst firing increases in a monotonic fashion, with increasing expected reward value.
Dopamine neurons also demonstrate slower, more sustained activations during the interval between a reward predicting stimulus and reward delivery. These encode the variance of the probability distribution, interpreted as the uncertainty associated with reward expectation. These tonic responses follow an inverted U-shaped doseresponse curve that is maximal at a probability of corresponding to the point of maximal uncertainty.