Recently, Parkinson's disease has emerged as an interesting model to understand the neurobiological mechanisms of the placebo response. In this case, patients are given an inert substance (the placebo) and are told that it is an antiparkinsonian drug that produces an improvement in their motor performance. A recent study used positron emission tomography (PET) to assess the competition between endogenous dopamine and [11C]raclopride for D2/D3 receptors, a method that allows identification of endogenous dopamine release (de la Fuente-Fernandez et al., 2001
). This study found that placebo-induced expectation of motor improvement activates endogenous dopamine in the striatum of parkinsonian patients. In addition, it has been found that expectations of poor versus good motor performance modulate the therapeutic effect of subthalamic nucleus stimulation in parkinsonian patients who had undergone chronic implantation of electrodes for deep brain stimulation (DBS). In fact, by analyzing the effect of subthalamic stimulation on the velocity of movement of the right-hand, the hand movement was found to be faster when the patients expected a good motor performance. These effects occurred within minutes, suggesting that expectations induce neural changes very quickly (Pollo et al., 2002).
The strong placebo responses in Parkinson's disease and the possibility to study parkinsonian patients who are implanted with electrodes for deep brain stimulation has been exploited recently to record from single neurons after placebo administration (Benedetti et al., 2004). In this study, the activity from single neurons in the subthalamic nucleus was recorded before and after placebo administration to see whether neuronal changes were linked to the clinical placebo response. The placebo consisted of a saline solution that was given to patients along with the suggestion that it was an antiparkinsonian drug. This procedure was performed intraoperatively after preoperative pharmacological conditioning with apomorphine, a powerful antiparkinsonian drug. It was found that the placebo responders showed a significant decrease of neuronal discharge and a reduction of bursting activity of subthalamic neurons, whereas the placebo nonresponders did not. Remarkably, as shown in Figure 2 for two representative patients (a placebo responder and a nonresponder), there was a nice correlation between the subjective reports of the patients, the clinical assessment of the neurologist, and the electrical activity of single neurons.
Thus, Parkinson's disease offers us an exciting and innovative model to understand the intricate relationship between expectations and neuronal systems. In particular, the possibility of recording from single neurons offers us the chance to identify the neuronal changes that take place in the basal ganglia circuitry during the placebo response.
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